Carlos Valencia is playing basketball and hopes to hold off on a marrow transplant a while so he can watch his beloved UA Wildcats. The drug that has suppressed Carlos Valencia's leukemia can't help him with his upcoming English exam. Gleevec, which Carlos takes at morning and evening, has reduced his leukemia dramatically, doctors say. Tucson teen's leukemia is at bay, lets him wait a little for transplant Carlos Valencia is trying to persuade his doctors to put off his bone-marrow transplant - needed to save his life, mind you - until spring, so he won't miss any of the University of Arizona basketball games. But he may actually get his crazy wish, now that a new "miracle drug" is working wonders on this well-known and much-loved Tucson teen, stricken for the second time with life-threatening leukemia, a cancer of the blood and bone marrow. The drug - Gleevec - may give Carlos, now 15, not only the basketball season he wants so much, but also vital extra time to search for elusive matching bone marrow to make the transplant work.
Approved for use in the United States only for the past two years, Gleevec is perhaps the closest thing to a "magic bullet" for cancer ever discovered. It targets chronic myelogenous leukemia (CML) - the type Carlos has been fighting for three years - and is already cutting into the disease's 50 percent mortality rate. Fully 80 percent of CML victims are achieving significant remissions on Gleevec, studies show. Before Gleevec, only 14 percent responded that well when taking the standard CML drug, interferon. Gleevec is the reason actor Ryan O'Neal, 62, is back in the movies and starring in a new television drama series, after being diagnosed with CML two years ago. O'Neal started taking the drug last year and is now in complete remission. As is Carlos today, after his leukemia returned three months ago, following a failed cord-blood transplant 2 1/2 years earlier. Carlos started taking Gleevec in late September. "He is in molecular remission - that is the highest degree of remission we can achieve," said Dr. Michael Graham, director of pediatric bone marrow transplantation at University Medical Center. "The most sensitive test we can perform has come back negative. We can detect no leukemic cells in Carlos now. We would have never seen this kind of response without Gleevec."
Gleevec was not available for Carlos during his first battle against leukemia, when his charismatic presence triggered the largest bone marrow donor drives ever held in Tucson. He is credited with singlehandedly bringing thousands of much-needed Hispanics into the national bone-marrow registry as potential donors. Developed during the past decade, Gleevec works in an entirely different way from standard, toxic cancer chemotherapy drugs. It directly blocks the abnormal protein that signals the overproduction of diseased white blood cells causing CML. As a result, the drug has few side effects and is easily tolerated by patients. Carlos feels some nausea for about 20 minutes after he takes his pills, in the morning and evening. "My energy is good. I've gained about 15 pounds, I'm playing basketball," said Carlos, a Salpointe Catholic High sophomore in the middle of exams. Flashing a smile, his now-long legs stretched out in front of him, he said, "There are no limits on me now." As his father, Ford Valencia, puts it, "His whole appearance is great - he's got his glow back. This is a wonder drug."
Most crucially for Carlos, Gleevec has so effectively fought off his leukemia that his doctors no longer feel the urgency they did a few months ago to get him transplanted as soon as possible. Once aiming for a November transplant, Graham now says it may happen in February or even later. "This is giving us a much larger window to look for a match for him, and I'm confident we'll be able to find something," Graham said. "We now have the time to look worldwide, at other ethnic groups that we think may provide a better match for him. "With how well he's doing on Gleevec, it's safe to postpone it while we figure out the best option for him."
It was the cruelest of ironies that despite the thousands of people who became potential bone-marrow donors at drives for Carlos, no bone-marrow match was ever found for him. Instead, he underwent a transplant using donated umbilical-cord blood, a more immature form of blood stem cells that do not require as close a match as actual bone marrow. But this time around, with Gleevec reducing his leukemic cells to apparently nil, Carlos will have a flying start at a successful transplant. "At his level of remission, there is a million-fold reduction in his leukemia burden," said Dr. Brian Druker, head of leukemia research at the Oregon Health & Science University Cancer Institute, who developed Gleevec. "The best news is we have looked at patients with even a thousand-fold reduction, and nobody has relapsed." There is even talk that Gleevec might prove a cure for CML. But with patients on it only a few years so far, it is too early to know if remissions will last for decades. "We're not counting it out," said Druker. "But right now, I think the combination of Gleevec and a bone-marrow transplant is the ticket for a cure."
Hearing Gleevec success stories like Carlos' gives Druker "an unbelievable feeling," he said. "You go to medical school hoping to help people, of course, and any physician takes great pride every day in doing that, and in improving the quality of people's lives," he said. "But for me, this goes beyond that. It's absolutely a dream come true. It's so amazing to hear that someone, the young man you are telling me about, is doing so well. I'll never get tired of hearing that." As he awaits his transplant, Carlos is maneuvering to make sure he misses not one UA basketball game, no matter when Graham decides to do it. Best case for Carlos is waiting until March, when the UA men's basketball team will likely reach the NCAA tournament and games will broadcast on network TV, which UMC gets in patient rooms. But if it happens earlier, when most regular season games are on cable stations, that would be a problem, since UMC TV's don't get those stations. "Right now, he's working on getting all the cable stations changed here at the hospital, in case that happens," said Graham, laughing. "But there's a chance we could put it off till March."
An unusually intensive assault on the cancer multiple myeloma - using two rounds of high-dose chemotherapy followed each time by a stem cell transplant - appears to double patients' long-term chances of survival, a study found. Although the approach is not a cure, doctors say the results are encouraging for victims of this usually lethal cancer of the bone marrow. The researchers found that after seven years, 42 percent of patients who got the double treatment were still alive, compared with 21 percent of those who received the standard single round of chemo plus a transplant. The head of a U.S. marrow transplant program said the French study is another important development in what has been an exciting year for multiple myeloma research, including federal approval in May of the drug Velcade, which targets one of the underlying defects that make this cancer grow. If such developments continue, "I'm very optimistic that we will be thinking of this as a curable disease within my professional career," said Dr. Edward Stadtmauer of the University of Pennsylvania's Abramson Cancer Center.
A transplant allows a higher dose of chemotherapy, because it puts the patient's stem cells back into the body to replace those killed by the treatment. Stem cells are a crucial component of bone marrow, which produces blood cells. The study, led by Dr. Michel Attal of Purpan Hospital in Toulouse and published in New England Journal of Medicine, looked at 199 patients who got two rounds of treatment, and 200 who got a single set. In addition to increasing life span, the second round of treatment doubled the chance of surviving seven years without a recurrence of cancer (20 percent versus 10 percent). The difference was most striking for people who had not had a good response to the first transplant. Only 11 percent of those patients lived seven years without a second transplant. With a second transplant, 43 percent survived that long. Stem-cell transplants are expensive - a single round can cost $150,000, about triple the cost of standard chemotherapy - and dangerous: Five people in each group died from the transplant itself.
"It may be that patients who are not doing well after a first transplant should automatically go in for a second transplant. That may be the most important lesson to get from that study," said Len Lichtenfeld, deputy chief medical officer American Cancer Society. Multiple myeloma is described both as a bone cancer and a blood cancer. It affects the plasma cells that make infection-fighting antibodies. Instead of making antibodies against a wide variety of diseases, the cells begin overproducing one and making too little of others. That leaves patients anemic, open to infections and susceptible to bleeding. Bones become painful and brittle. Other proteins interfere with kidney function. A half-century ago, diagnosis meant almost certain and swift death. Now, treatment can help many patients at least feel better for a while and fight off infections, keeping them alive for years and even decades.
The cancer pill Gleevec, which has produced striking results in patients with chronic myeloid leukemia, may also help some patients with another form of leukemia which is hard to treat, U.S. researchers reported. The drug, made by Swiss pharmaceutical giant Novartis, helps starve tumors and is being tested against a range of cancers. Research being presented at the American Society of Hematology meeting in San Diego suggests it could help patients with acute lymphocytic leukemia, also called ALL. A team at the University of Texas M. D. Anderson Cancer Center paired Gleevec with high-dose chemotherapy in patients with Philadelphia-positive ALL. Both CML and this type of ALL are caused by a break in the so-called Philadelphia chromosome, named after the city where the abnormality was discovered. Philadelphia-positive ALL accounts for one-fifth of all cases of the leukemia, and is not easily cured. Only 12 percent to 28 percent of patients are still alive two years after diagnosis even when they are treated with high doses of chemotherapy. Their chances are better if they can get a bone marrow transplant from a closely matched donor, but many patients do not have such a donor.
Dr. Deborah Thomas and colleagues tested 24 patients with ALL, giving them Gleevec on top of standard chemotherapy. Her team found that 23 of the patients went into complete remission after a single three-week course of the pills. The remissions have, so far, lasted up to 29 months after treatment. She said larger studies are needed before it is clear how much Gleevec helps these patients. The break in the Philadelphia chromosome results in the production of an abnormal protein that causes overproduction of white blood cells. Gleevec, sold as Glivec in Europe, blocks production of the abnormal protein. The study is one of many that shows cancer therapy in the future will be tailored to individual patients. Dozens of different genetic defects can cause cancer and while some drugs work well in many patients, they may not help others with the same form of cancer because the underlying causes are different. ALL affects 3,800 people a year in the United States and kills 1,400.
Aplastic anemia and other related bone marrow diseases are relatively rare in the United States, with about 40,000 new cases occurring each year. But research into the diseases -- in which the body slows or stops the production of healthy blood cells -- could help provide insight into more prevalent health problems, such as heart disease, researchers say. To heighten awareness about the conditions, Dec. 1-7 has been designated National Aplastic Anemia Awareness Week. In addition, the National Institutes of Health recently awarded a $4.5 million grant to spur additional research. The Cleveland Clinic Foundation and Dr. Jaroslaw P. Maciejewski will use the money to create a clinical research center dedicated to studying the bone marrow disorders. The diseases have attracted federal support, in part, because they involve damage to stem cells. And stem cells have attracted much research attention due to their potential regenerative powers and ability to transform themselves into a host of different cells. "There are scientific reasons to use rare diseases in studies because they provide clues to treating more common diseases," Maciejewski says of his research. "For example, bone marrow is one of the best places to learn more about adult stem cells and their regenerative properties."
There are many rare bone marrow diseases, but the most common are aplastic anemia and myelodysplastic syndromes, or MDS. The symptoms of these diseases tend to be extreme versions of common medical problems, says Marilyn Baker, executive director of the Aplastic Anemia & MDS International Foundation Inc. For example, a victim might suffer from drastic bruising. "You open a pickle jar, and the next day your hand is all bruised and swollen," she says. Other symptoms could include hemorrhaging, extreme fatigue and chronic illness. "To one of our patients, a cold would never go away and would turn into pneumonia," she says. Baker cautions that people suffering these symptoms do not necessarily have bone marrow disease. They should ask their doctor for a simple blood test that can determine whether they do.
Aplastic anemia occurs when the bone marrow stops making enough blood cells, leaving the marrow almost empty of blood-forming cells. About 1,000 new cases of the disease appear each year in the United States. MDS happens when bone marrow begins producing poorly functioning or immature blood cells. This disorder is more common, with about 20,000 to 30,000 new cases each year. Doctors have little idea what causes the diseases. "The strange thing about this is there is no smoking gun," Maciejewski says. Some known potential causes are exposure to radiation or toxins. "Sometimes cancer patients get our disease as a result of their radiation treatment," Baker says. "Others have been exposed to benzene, pesticides or insecticides."
As recently as 20 years ago, aplastic anemia was considered fatal, but advances in drug therapies and bone marrow transplantation have allowed doctors to extend the lives of victims by years. Remission rates now are 60 percent to 80 percent, up from about 30 percent a decade ago, Baker says. "It is still often fatal," she says. "The president of our association has lived with the disease for 13 years, but there are other patients I know who pass away within six weeks." MDS sufferers are less fortunate. Remission rates have not improved, although care has improved and the number of clinical trial opportunities has also increased, Baker says.
Standard treatment for bone marrow failure diseases involve bone marrow transplants and immunosuppressive drug therapy. For patients who can't benefit from those treatments, experimental options are available. Most sufferers must undergo regular blood transfusions. The diseases are highly specialized, Maciejewski says, meaning that specific treatment often depends on the individual sufferer. "If a patient is 10 years old, you wouldn't think twice before going to transplantation," he says. "If the patient is 70, you think three times before going there." Because the diseases are so rare, and because complex decision-making is necessary in choosing the right treatment, experts urge patients to work with a hematologist who specializes in the specific bone marrow failure disease in question. The $4.5 million grant is part of an overall NIH effort to increase research into rare diseases. Other centers in the NIH Rare Disease Research Network will study rare lung conditions, nervous system disorders and rare genetic steroid disorders.
Psoriasis sufferers may later develop lymphoma cancers at nearly three times the rate of people who do not have the red and scaly skin condition, a study said. The reason for the greater risk is not clear, said the report from the University of Pennsylvania in Philadelphia. "Additional studies are necessary to determine if the increased rate of lymphoma is related to psoriasis severity, psoriasis treatment, or an interaction" of various factors, concluded the report published in the November issue of the Archives of Dermatology. Researchers said they reached the conclusion by looking at a random sample from a British database that holds medical records for more than 8 million patients. The records involved people of 65 or older who were treated between 1988 and 1996. "Patients with psoriasis had an almost three-fold increased rate of lymphoma compared with patients without psoriasis," the authors concluded. "Patients 65 years or older who had psoriasis developed an additional 122 lymphomas per 100,000 patients annually."
Psoriasis is a common skin disease characterized by patches of thickened, red and scaly skin, usually on the torso or arms. It can be painful and disfiguring in some cases and affects from 1 percent to 2 percent of the population. The article said there had been previous research indicating psoriasis victims were at higher risk for lymphoma but the degree of the risk had not been measured. Lymphoma is a general word categorizing a variety of cancers of the lymphatic system.
According to results recently published in the journal Blood, the anti-angiogenesis agent SU5416 has demonstrated anti-cancer activity in the treatment of refractory acute myeloid leukemia. Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood characterized by the rapid uncontrolled abnormal growth of immature white blood cells (immune cells), which never develop into functioning cells. Besides not being able to carry out the functions of mature immune cells, AML cells may also crowd out normal blood cells in the bone marrow and blood. AML is considered to be an aggressive cancer and patients are often at a high risk of developing a cancer recurrence following therapy, particularly if they are not able to undergo high doses of therapy. However, chromosomal variables of AML cells as well as levels of cancer cells in the blood further distinguish patients into being at a high-risk, standard-risk or low-risk of developing a cancer recurrence and treatment may be altered according to these stratifications. Patients with AML that has stopped responding to standard therapies (refractory) or elderly patients who are not able to tolerate standard chemotherapeutic approaches are left with limited treatment options.
A new arena of cancer research involves the inhibition of angiogenesis. Cancer cells require food, oxygen and growth proteins in order to grow and spread. These essential nutrients are transported to the cancer cells by blood vessels. Angiogenesis is a complex process of creating new blood vessels necessary to transport "food" to the cancer cells. Two key proteins that are necessary for the process of angiogenesis are called matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF). One of several properties of VEGF includes the stimulation of endothelial cells (cells comprising the innermost layer of blood vessels) to replicate and migrate from existing blood vessels to the cancer. Endothelial cells secrete MMPs, which create an opening in existing tissues surrounding the cancer, allowing the endothelial cells to move near the cancer and form new blood vessels to "feed" the cancer.
SU5416 is a novel angiogenesis inhibitor still being evaluated in clinical trials. SU5416 produces its anti-angiogenic effects by binding to VEGF receptors on cancer cells, which inhibits the action of VEGF. This halts the growth of new blood vessels necessary to promote cancer cell growth. Moreover, VEGF is expressed in a wide variety of tumor types and has been associated with expression in immature cells in the bone marrow, called stromal cells, which are associated with the cancer. A recent multi-institutional clinical trial was recently conducted to evaluate SU5416 in the treatment of AML. This trial involved 43 patients with either refractory AML or elderly patients with AML who were unable to tolerate standard chemotherapy. Following therapy with SU5416, 8 patients achieved an anti-cancer response. The duration of response lasted between 1-5 months. Researchers noted that patients with high levels of active VEGF had a significantly improved rate of anti-cancer activity than those patients with lower levels. The researchers concluded that the concept of anti-angiogenesis may be applicable in the treatment of AML, particularly for those who have stopped responding to, or who cannot tolerate standard therapies, as effective treatment agents are limited for this group of patients and no real therapeutic improvements have been made for 2 decades. The authors also state that a different dosing schedule or perhaps pre-testing for VEGF may provide improved results. Patients with refractory AML or those unsuitable for standard therapeutic approaches may wish to speak with their physician about the risks and benefits of participating in a clinical trial evaluating anti-angiogenesis agents or other novel therapeutic approaches.
Combining the drug Velcade (bortezomib) with experimental drugs called histone deacetylase inhibitors may help patients with chronic myelogenous leukemia, a malignant cancer of the bone marrow and one of the most common forms of leukemia. A study by Virginia Commonwealth University researchers says this combination appears to stop the growth of cancer cells by blocking key enzymes. That action kills leukemia cells, including those that have become resistant to other chemotherapy drugs. The findings appear in the Nov. 15 issue of Blood.
"We found that this combination was quite lethal to chronic myelogenous leukemia cells, which are generally resistant to standard chemotherapy agents," the authors write. "On its own, Velcade has not been shown to be an effective treatment option for this form of leukemia. However, Velcade and histone deacetylase inhibitors appear to interact synergistically to induce cell death in chronic myelogenous leukemia, at least in the test tube, thus representing a novel treatment approach," they add. The research is still in the early stages, but the scientists say their initial laboratory results are encouraging.
Formaldehyde, the pungent chemical used in everything from insect preservation to film manufacturing, may boost rates of leukemia in exposed workers, a major federal analysis finds. And a new study from the United Kingdom suggests such workers also face a greater lung cancer risk from formaldehyde exposure, although they only face a tiny risk of some rarer cancers. While the U.S. researchers acknowledge other studies haven't been as definitive about the potential risk, the new reports are certain to fuel the debate over the use of the chemical in American factories. Federal regulations have limited exposure to formaldehyde since the 1980s. However, some experts continue to call for less research and more restrictions.
For the U.S. study, Michael Hauptmann, a biostatistics researcher at the National Cancer Institute, and his colleagues launched the largest-ever analysis of formaldehyde exposure. They examined the medical records of 25,619 workers who began working with formaldehyde before 1966 at 10 industrial plants. Researchers followed the workers through 1994. Those exposed to high levels of formaldehyde were up to 3.5 times more likely to develop leukemia than those at the lowest levels. In total, 69 of the those workers died of leukemia. While the number of deaths is small, the link between formaldehyde and leukemia is important, Hauptmann says. "The study definitely suggests that exposure should be kept to a minimum in the workplace and the environment," he adds. The number of American workers exposed to formaldehyde on the job appears to be unknown, but federal officials estimated the number at 1.5 million from 1981-1983.
Most of the workers are exposed to formaldehyde during various types of manufacturing, including the production of particle board, plywood, plastic and photographic film, Hauptmann says. Scientists and pathologists also work with formaldehyde, which acts as a preservative and gives laboratories their distinct smell. Other uses include the manufacture of permanent press clothing, embalming fluid and cosmetics. "It usually comes in a liquid form from which solutions are prepared," Hauptmann says. "Then there is formaldehyde gas released that you can inhale." His findings appear in the Nov. 5 issue of the Journal of the National Cancer Institute.
In the other study, which appears in the same issue, researchers in the United Kingdom examined the medical histories of 14,014 British men who were exposed to formaldehyde after 1937. The study had been completed in the late 1990s, but the researchers extended it to 2000. Research in animals has suggested that formaldehyde could contribute to two rare types of nasal cancer, but the number of deaths from them -- three -- were actually lower than those that would have otherwise been expected. However, the workers were up to 1.6 times more likely to die of lung cancer. It's not clear how formaldehyde may lead to leukemia and lung cancer. One possibility is that the chemical launches itself into the body on tiny particles in the air and then works itself free to create damage, Hauptman says. Epstein says both findings are "more than enough to warrant the toughest regulatory proposals."
Britain's Department of Health said that 5,000 women successfully treated with chest radiation for Hodgkin's disease in England over the past 40 years could be at increased risk of developing breast cancer. It said cancer centers had been asked to contact the women and offer them regular breast screening so that any cancers they develop are detected and treated early. Professor Mike Richards, the National Cancer Director, said the UK was believed to be the first country to mount a national screening program following research showing radiotherapy increases Hodgkin's disease patients' long-term risk of breast cancer. In a statement, the department said experts estimated that women treated in childhood had a one-in-three to one-in-seven risk of developing breast cancer over the next 25 years. The risk was slightly lower at one-in-four to one-in-seven for women treated in their 20s.
Hodgkin's disease is an uncommon malignancy of the lymphatic glands. It usually affects people in their 20s to late middle age. More than 80 percent of patients survive at least five years. Richards stressed that radiotherapy was a life-saving therapy and that no errors had been made in the women's treatment. "Without radiotherapy, many of these patients would have died," he said. "However, we now know that more of these patients are developing breast cancer than would normally be expected. That is why we are taking action to alert patients and to offer them screening to try and pick up any cancers early." Nowadays, doctors often use lower doses of radiation in combination with chemotherapy, as this is thought to provide a safer cure for many cancers. Radiation can cause mutation of the breast cells, particularly when given to young women. A study published in July in the Journal of the American Medical Association showed that of 3,817 women with Hodgkin's disease, 105 or nearly 3 percent, eventually developed breast cancer. But women who had undergone only chemotherapy treatment with an alkylating agent, a drug that inhibits cell division, had a 40 percent lower risk of breast cancer. Those who received a combination of radiation and chemotherapy still had a 1.4-fold higher risk, though the risk declined the more the drug was used.
Even though overall survival rates for childhood leukemia have improved dramatically since the 1960s, children of all races are not benefiting equally, researchers at the University of Minnesota and elsewhere have found. Black, Hispanic and American Indian children who develop the most common form of the disease still don't do as well as white and Asian kids, according to the study. Researchers don't know whether the poorer outcomes for youngsters with acute lymphoblastic leukemia are due to socioeconomic factors or differences in the way the body responds to standard chemotherapy treatments, said James Gurney, a research epidemiologist who is also an associate professor of pediatrics and a member of the University of Minnesota Cancer Center.
A high-precision radiation therapy for cancer that can be used to treat leukemia patients and children will be developed commercially for the first time and could reach hospitals in three years, a Siemens executive said. The technology, for which German industrial conglomerate Siemens bought the license this week, precisely targets tumors that were previously too dangerous to treat with radiation, the executive of the company's medical division said. "We're talking primarily about chondrosarcomas (tumors of cartilage cells), brain-stem, eye and pediatric cancers, leukemia," Medical Executive Vice President Hermann Requardt told Reuters by phone. He said an extra five to 10 percent of cancers would be treatable with the new type of radiation.
The technique destroys cancerous cells by shooting so-called "heavy ions" at them at extremely high speeds. A particle accelerator fires out charged Carbon-12 nuclei which are guided precisely to their target by magnetic fields, sparing surrounding tissue and organs. The technology was developed by German particle physics research institute GSI in conjunction with partners including the German Cancer Research Center and Heidelberg University and was tested in the German city of Darmstadt. "Since 1997, approximately 200 patients participating in a clinical study were successfully treated with this method," GSI and Siemens said in a joint statement. "The results exceeded our expectations, since we were able to observe a very quick as well as lasting tumor reaction in these patients," Juergen Debus of Heidelberg University said in the statement.
The cost in treatment alone of heavy-ion radiation has been estimated as being at least twice that of conventional radiation treatment. But Requardt said that factoring in potentially shorter treatment times and higher success rates -- saving on prophylactic care -- the costs could be roughly comparable. "There will be a strong desire to go for this very patient-friendly therapy," he said, adding that it could be carried out on an out-patient basis. Siemens still has a few legal and regulatory steps to go through before it will start building the machines but Requardt said he did not foresee any difficulties. "We don't see any major hurdles," he said. "The plans are ready and after ground-breaking we expect it will take three to four years before we can start," he said. He added that the company already had strong interest from investors and might finance the initiative privately with an initial investment of up to 100 million euros ($117 million). Requardt said it would cost around 30 million euros to build each machine, and that the first commercially working system would probably be in Germany, which has a mixture of public and private health care. The new technology will complement Siemens' existing portfolio of medical products which includes X-ray, magnetic imaging and monitoring equipment. "The technology brings a precision of millimeters into the tumour treatment and to do that you have to know exactly where the organs are," he said. ($1=.8522 Euro)
Leukemia, lymphoma and myeloma: All three are blood cancers that can be fatal if left untreated, and yet none can be halted with surgery. Until now, that has left chemotherapy as the first line of defense. But new molecularly targeted drugs are being hailed as precise and powerful weapons against cancers that are notoriously hard to treat. "Unlike solid tumors, where surgery can be used to remove the tumor at an early stage and the patient might not be treated with anything else, we can't do that in blood cancers," explains Alan Kinniburgh, vice president of research at the Leukemia & Lymphoma Society. "This was the first place chemotherapy was brought to bear and was successful. We're now at a point from where in 1960 about 4 percent survived longer than five years and now 85 percent do," Kinniburgh says. To push beyond that 85 percent mark, researchers are pouring their energy into the development of these molecularly targeted drugs, which attack diseased cells directly and produce fewer side effects in the process.To heighten awareness of these developments, the Leukemia & Lymphoma Society has also declared September as Leukemia, Lymphoma and Myeloma Awareness Month.
More than 100,000 Americans will be diagnosed with one of these three blood cancers in 2003. That's not counting hundreds of thousands more who are living with one of the diseases. Lymphoma is the most common type of blood cancer, representing 57 percent of all cases. Leukemia makes up 30 percent of all cancers diagnosed in children under the age of 15. Leukemia refers to cancer of the bone marrow and blood cells. The two major categories are myelogenous and lymphocytic. Each of these can be further subdivided into acute (with a rapid onset) and chronic (which comes on more slowly). Lymphomas are cancers that arise when lymphocytes -- a type of white blood cell -- become malignant. The two main types of lymphoma are Hodgkin's and non-Hodgkin's. Myeloma affects the plasma cells, or white blood cells found primarily in the bone marrow, and it interferes with the body's immune system.
No one is sure what causes these cancers, although they are thought to arise when a single cell with a genetic flaw starts replicating uncontrollably. While chemotherapy and other conventional treatments are still being used, the breakthroughs are happening with molecularly targeted drugs. "We've really spent a lot of time in the last couple of decades finding altered genes in cancer and now we're actually starting to develop molecular-targeted therapy to go after these altered genes," says Dr. Donald Small, an associate professor of oncology, pediatrics and cellular and molecular medicine at the Johns Hopkins University School of Medicine.
Specifically, scientists are looking at a class of frequently mutated genes called tyrosine kinases, which seem to be involved in many of the blood cancers, Small says. Chronic myeloid leukemia, or CML, for instance, involves a genetic flaw in one of these genes that produces an abnormal protein. This triggers a signal that pushes cells to start reproducing. A new drug, Gleevec, goes inside the abnormal protein and commands it to stop sending the signal. Because the drug is so finely targeted, it has few side effects. Gleevec now appears to be emerging as the drug of choice for CML, Small says.
Similarly promising research is taking place with acute myelogenous leukemia, or AML, a disease whose cure rate hovers at 20 percent to 30 percent. "It requires such intensive chemo that a lot of people consider patients over 60 or 65 can't be treated aggressively enough to have any chance," Small says. "We really need new types of therapies and it may well be that, when chemo is combined with some of the targeted therapies, we could see a big impact." Small and other researchers around the country are currently conducting trials with new molecularly targeted drugs that inhibit another tyrosine kinase gene, this one called FLT-3. "There are patients who are having responses," Small reports. In the case of AML, however, more than one drug will probably be needed to affect the multiple genes that are at fault. "In chronic phase CML, it's probably a single gene, so it's a lot easier to target; you're basically hitting the whole disease," Small says. "In AML, there are probably three or four or more altered genes."
There are other categories of therapy as well. Chemotherapy and radiation have both been around for half a century but can entail significant side effects. "They kill growing cells and they kill the fastest first and that's fine, but it's kind of a blunt instrument when it's used," Kinniburgh says. A newer approach is called immunotherapy, also targeted but not usually considered molecularly targeted. This involves developing antibodies that attack part of the cell surface, causing the cell to die. These are also called monoclonal antibodies. And vaccines could help the patient's own immune system fight off blood cancer. No vaccines are yet approved, though some are in advanced clinical trials. Many patients also need bone marrow transplants, which seek to replace a person's depleted healthy blood-forming cells with another person's. "It's kind of a hybrid system of using someone else's immune system to reconstitute your own immune system after very vigorous chemo and/or radiation," Kinniburgh explains. "You just have to watch out for those cells attacking the body because there are differences. It kills patients every day."
Finally, there have been some recent reports that postmenopausal women who take aspirin regularly may have a lower incidence of acute leukemias. Mostly, though, the world is moving in the direction of highly targeted treatments. "Over time it will be more and more designer-type therapy," Small says. "Eventually, it may turn out that a patient comes in with a certain type of tumor. We take cells, see what genes are altered and pull compound A for this mutation and compound C for that one. It will be very, very specific and very much designer-type therapy."
Young adults who get mononucleosis, the "kissing disease," have more than double the risk of developing a rare type of cancer, a Danish study found. Doctors have long suspected a link between mononucleosis and Hodgkin's disease, a highly treatable cancer of the lymph system. But the role played by the common virus that causes mono was uncertain. The virus, Epstein-Barr, is found in about one-third of Hodgkin's tumors. In a study of over 63,000 young adults suspected of having mono, the researchers found that those who got mono had a higher-than-average chance of getting Hodgkin's, and the risk lasted for two decades. There was no increased risk for those who did not have mono. "I think it removes the last shade of doubt that the virus actually has something to do with causing Hodgkin's disease," said Dr. Richard Ambinder of Johns Hopkins School of Medicine, who was not involved in the research. "The flip side to that is that everyone's got the virus, so it can't possibly be the whole story."
The Danish researchers stressed that Hodgkin's disease, also known as Hodgkin's lymphoma, is uncommon. About one in 1,000 of young adults with mono will get the cancer, they said. "Only in rare circumstances will this lead to the development of Hodgkin's lymphoma. So there's no reason for any panic," said Dr. Mads Melbye, one of the researchers at Statens Serum Institut, the Danish equivalent of the U.S. Centers for Disease Control and Prevention. The study is reported in New England Journal of Medicine. Hodgkin's accounts for less than 1 percent of cancer in the United States, and is most common in those ages 15 to 34 and those over 55. According to the American Cancer Society, about 7,600 new cases will be diagnosed this year.Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, said parents and patients should not be overly concerned about the study's findings. "This doesn't change our practice or our patterns. It enhances our knowledge," Lichtenfeld said. Ambinder said the research raises the possibility of preventing Hodgkin's in those who have had mono or diagnosing it earlier. "There's fertile ground for more research," he said.
Most everyone is infected at some point with the Epstein-Barr virus, which is spread through saliva, and the virus remains dormant for life. In children, there are usually few or no symptoms from the infection. But when exposure first occurs in adolescence or later, it can cause mono. Symptoms include fever, sore throat, swollen glands and fatigue. The research included 38,555 Danish and Swedish patients diagnosed with mono and 24,614 Danish patients who were tested for mono but did not have it. Cancer registries were checked to determine how many later developed Hodgkin's disease, which typically occurred four years after mono. Sixteen of 29 Hodgkin's tumors tested from the mono group contained the virus. The findings suggest that there are other causes for Hodgkin's besides the Epstein-Barr virus, Melbye said. "It's a cause, not THE cause," he said. Melbye said the study's results should apply to the United States, which has rather similar rates of mono and Hodgkin's.
Survivors of childhood cancer are much more likely than their healthy siblings to suffer from a variety of health problems when they reach adulthood. The increased risk was particularly pronounced among women, those with lower educational levels, and those with low household incomes. These results, from an unprecedented study of almost 10,000 cancer survivors, appears in the Sept. 24 issue of the Journal of the American Medical Association. Because survival rates for childhood cancers are now upwards of 78 percent, the number of people who have lived five or more years beyond their initial diagnosis is growing. For the first time, scientists and the world can see the long-term consequences, which can include second cancers, heart disease, infertility, obesity and psychological distress.
The authors of this study compared the health status of 9,535 adult participants of the Childhood Cancer Survivor Study with 2,916 of their siblings. All of the cancer survivors had survived at least five years after their diagnoses. Six areas of health were assessed: general health, mental health, functional status, activity limitations, cancer-related pain and cancer-related anxiety or fears. The first four areas were assessed in the sibling control group. Participants were asked to give their own perceptions of their health status, something that distinguishes this study from many others. According to this self-reported data, cancer survivors were 2.5 times more likely to report adverse general health, 80 percent more likely to report mental health problems, 2.7 times more likely to report limitations in activity, and 5.2 times more likely to report functional impairment, compared with their siblings. Compared to male survivors, females were 40 percent more likely to report at least one adverse health effect, 20 percent more likely to have general health problems, 40 percent more likely to have functional impairment, 70 percent more likely to suffer activity limitations, and 60 percent more likely to suffer from anxiety. Survivors with a lower educational level were 2.6 times more likely to have general health problems, while those with an annual income of less than $20,000 were 1.8 times more likely to report such problems. Almost half (44 percent) of the survivors reported adverse effects in at least one of the six areas. On the other hand, only 10.9 percent perceived they had impaired health.
"The vast majority perceived their health as very good, which is testimony to how resilient they are after this experience," says study author Dr. Melissa Hudson, director of the After Completion of Therapy Clinic at St. Jude Children's Research Hospital. "[Having cancer] affects them emotionally, psychologically and physically, and the vast majority are able to move beyond that cancer experience and adapt to whatever chronic illnesses or disabilities they have." But the U.S. health-care system is not set up to handle the long-term health problems that do arise. "There's really not a very good system in this country for providing long-term care," says Dr. Cindy L. Schwartz, author of an accompanying editorial and an associate professor of oncology and pediatrics at the Johns Hopkins Kimmel Cancer Center in Baltimore.
Kids with cancer become adult survivors who are no longer allowed by health insurers to visit their treating institution. Many adults move to other geographical locations. At the same time, Schwartz adds, the disease and treatments tend to be unique and most primary-care providers do not have the knowledge or experience to deal with them. In some cases, the idea of long-term survivors is relatively new, so experts aren't even sure what to expect. "It's an ongoing, moving target," Schwartz says. "The problem with late effects is that many are things that don't show up for 10 or 15 years . . . It would be nice to be able to prepare [survivors] as to what they might expect." As it stands, however, good mechanisms for such follow-up do not exist. "We're trying to make the medical community aware of this," Hudson says. "This is such a small percentage of each individual primary-care provider's practice. We want to make this as easy as possible for primary-care providers. We want them to know where resources are without becoming an expert."
According to recent results published in The New England Journal of Medicine, children diagnosed with acute lymphoblastic leukemia (ALL) who receive treatment including radiation therapy to the brain are at an increased risk of suffering long-term side effects. Acute lymphoblastic leukemia (ALL) is a cancer of the bone marrow and lymph system. The bone marrow produces early blood-forming cells, called stem cells, which grow and mature into the three blood cell types: white blood cells, which fight infection; red blood cells, which carry oxygen to tissue; and platelets, which help blood to clot. ALL is characterized by uncontrolled production of immature lymphocytes (white blood cells), of which there are two types: B and T cells. These immature lymphocytes never mature enough to perform their specific function of fighting infection. In addition, these rapidly dividing cells crowd out and suppress the formation of other important blood cells, such as red blood cells, platelets and other white blood cells. ALL is an aggressive cancer that must be treated aggressively for optimal chances of a cure.
The central nervous system (CNS), including the brain and spinal column, is a common site for cancer to recur in patients with ALL. Historically, patients were treated with radiation to the brain alone or brain and spinal column to reduce the risk of a recurrence in the CNS. Due to known long-term side effects that can be caused by irradiation to the CNS, present treatment for the prevention of a recurrence in the CNS is chemotherapy delivered systemically (full-body) or intrathecally (spinal column). Researchers from St. Jude Children's Research Hospital have recently compared long-term side effects of patients who had received or not received radiation to the brain for treatment of childhood ALL.
This study involved 856 patients who had survived at least 10 years following treatment for ALL; 597 of whom received radiation therapy and 259 who had not. The risk of developing a second cancer was 21% in patients who received radiation therapy, compared with less than 1% in patients who did not receive radiation. Survival at approximately 30 years following treatment was 95.3% in the group of patients treated with radiation therapy, compared with 98.3% in patients not treated with radiation, which is the approximate survival rate of the general population. Furthermore, patients treated with radiation therapy had significantly higher than average rates of unemployment and women in this group were less likely to be married. The researchers concluded that brain and spinal radiation therapy in childhood patients diagnosed with ALL can lead to long-term consequences, including an increased risk of developing a second cancer. Since the vast majority of pediatric patients treated for ALL achieve long-term survival, it is important for both patients and physicians to be aware of long-term sequelae of CNS radiation. Patients who are survivors of childhood ALL and received CNS radiation should discuss risks associated with this therapeutic regimen with their physician.
Children's chances of beating cancer have gotten better but as many as two-thirds of survivors are likely to experience a delayed side effect from the disease or the treatment, said a report. About a quarter of survivors may experience severe or life-threatening side effects that do not show up immediately but could affect things like growth, fertility, heart function, muscle movement or cognitive activity, said the study by the Institute of Medicine, an arm of the National Academy of Sciences. Susceptibility to these late side effects depends on the child's age at the time of diagnosis, how much chemotherapy and radiation were used as well as the severity and location of the cancer. The late side effects can occur in follow-up treatment or they may develop in adulthood, complicating their identification and treatment, the report said.
Also, because treatments for cancer have evolved in recent years, the delayed side effects are also changing. In 1997, 270,000 Americans of all ages had survived childhood cancer - including about 1 in 640 adults aged 20 to 39. That was up from 1970, when children diagnosed with cancer had little chance of being cured. The rising number of survivors has made the long-term care issues more apparent. "We're learning more as the first generation of childhood cancer survivors get older," said Stuart Kaplan, a staff physician in a follow-up cancer care clinic at St. Jude Children's Research Hospital in Memphis, Tenn. Looking for known threats and treating side effects early can help to minimize the damage these side effects can cause, he said. "Directed screening is very important, and it's really the job of the primary care providers," he said, adding that educating patients is also important "because the onus is often on them."
The report recommends:
for the follow-up care of childhood cancer survivors. -Creating links
between primary physicians and specialists.
Two new studies show radiation can affect how long and how well children survive cancer. The first study found children with acute lymphoblastic leukemia who received chemotherapy but not radiation to the brain area tended to live longer and with a better quality of life than those who got both treatments. But the long-term outcomes for both groups were quite high.
The second study found the risk of hospitalization for psychiatric disorders is no higher among survivors of cancer in childhood or adolescence. The one striking exception was among those who had had brain tumors, for which radiation is the standard treatment. Both reports appear in the New England Journal of Medicine. "Neither [study] has anything smashingly new to say, but they are good studies because they involve a relatively large number of patients that confirm some things that we already knew to some extent," says Dr. Joseph V. Simone, author of an accompanying editorial.
Referring to the first study on children with acute lymphoblastic leukemia, Dr. William Carroll, division chief of pediatric oncology at New York University Medical Center, says, "Cure rates for childhood leukemia are one of the success stories." "The question has been now that we're curing all these patients, what problems are going to surface 20, 30 years later," he adds. "This study shows quite strikingly that the survival of these patients is no different from the general population so once you've gone that long you should be considered normal. And that has profound implications for everything from getting insurance to how you're viewed in society. When we say cure, we mean cure."
According to the National Cancer Institute, acute lymphoblastic leukemia, or ALL, is the most common form of leukemia in children and the most common type of childhood cancer. Patients suffering from this disease have too many underdeveloped white blood cells. The research team looked at 856 patients who had been treated in clinical trials at St. Jude Children's Research Hospital in Memphis between 1962 and 1992. The patients, all of whom had survived at least 10 years, were divided into two groups: Those who had received radiation and those who had not. Participants who did not receive radiation therapy and who had survived to the 10-year mark without any new or recurring illness can expect to live a normal life, the authors conclude. "Normal" refers both to length and quality of life. "Patients who never received radiation to the brain had normal survival compared to the general population," says study author Dr. Ching-Hon Piu, director of the Leukemia Lymphoma Division at St. Jude. "Employment and marriage rates were the same as the general population, as well as insurance rates."
The mortality rate for the group that received radiation was slightly higher than the general U.S. population. While men and women in the radiation group had health insurance rates similar to the general population, they had higher unemployment rates. In the radiation group, 15.1 percent of men were unemployed, compared to 5.4 percent of the general population. And 35.4 percent of women were unemployed, versus 5.2 percent of the general population. Women who had received radiation were also less likely to be married (only 35.2 percent were married, versus 48.8 percent of the general population). Piu attributes these differences to brain damage resulting from the radiation treatments.
For the second study on hospitalization for psychiatric disorders, the study authors, based in Denmark, looked at 3,710 people who had survived at least three years after being diagnosed with cancer in childhood or adolescence. Although more people in this group were hospitalized for a psychiatric condition than would be expected in the general population, that higher number was entirely due to brain tumor survivors. These individuals were 80 percent more likely to be hospitalized. "We've known for 15 or 20 years that a child, depending on the [type of cancer] and the age of the child, runs a risk of neuropsychosocial effects," Simone says. "We've spent a long time figuring out what it is about the radiation to try to refine treatment." Largely as a result of this long-running research, radiation is no longer used as a primary treatment for most childhood cancers (the notable exception being brain cancer). "We know now that with chemotherapy these kids do fairly well so there's really no need to irradiate them unless they have overt central nervous system disease," says Dr. Shipra Kaicker, a pediatric hematologist/oncologist at Maimonides Medical Center in New York City.
The point, Simone says, is that follow-up is necessary to assess and improve upon treatment for childhood cancer. The psychiatric study was possible because of the exceptionally thorough health-care records kept in Denmark, which has universal health care. In the United States, many patients are lost to follow-up, suggesting the need for more systematic methods for following childhood cancer patients. Simone cites a report due out in October from the U.S. Institute of Medicine that will try to provide a road map for studying these individuals.
Acute lymphoblastic leukemia (ALL), the most common type of childhood cancer, can be cured and kids who survive it can have a normal lifespan, new research suggests. ALL involves the uncontrolled growth of blood cells called lymphocytes. About 3000 children are diagnosed with ALL each year in the US. ALL is slightly more common in boys than girls and it is usually diagnosed between three and five years of age. "We were interested in determining whether patients with ALL could be cured," lead author Dr. Ching-Hon Pui, from St. Jude Children's Research Hospital in Memphis, Tennessee, told Reuters Health. "The disease is associated with late relapses, but now with 30 years of follow-up, I think we can confidently say that indeed ALL can be cured."
In the past, children who were treated and went five years with no return of their disease were classified as cured, Pui noted. The new findings, however, indicate that 10 years without disease is needed before a patient can be considered cured, he added. The current results are based on a study of 856 ALL patients who were treated between 1962 and 1992. All of the patients had survived at least 10 years with no return of their cancer. The findings are reported in The New England Journal of Medicine.
ALL patients treated with chemotherapy lived just as long as healthy individuals. The patients who also received radiation--a treatment often given to high-risk patients--had slightly lower survival. Treatment with radiation was also tied to other problems, the investigators point out. For example, such therapy seemed to raise a patient's chances of developing other cancers. "This is the first study to show that the adverse effects of radiation can occur 20 to 30 years after treatment," Pui said. "We really didn't appreciate that patients could develop (other cancers) beyond 20 years." Still, in general, the cancers that arose were not that serious and were easily treated, he added. "A study is currently underway at St. Jude to see if we can avoid (using radiation) in high-risk ALL patients," Pui noted. So far the results look encouraging, he added.
Doctors have long known that radiation therapy increases the risk that people with Hodgkin's disease might develop other forms of cancer, including blood malignancies and solid tumors. In young women with Hodgkin's disease, the threat of breast cancer is a particular concern following radiation. But new research suggests this hazard can largely be avoided with careful attention to the hormones of women undergoing treatment for Hodgkin's disease. In particular, drugs that interfere with the sex hormone estrogen -- such as the cancer drug tamoxifen -- may help. "Tamoxifen has not been used in this population, but it might be something that we should consider," says research leader Flora van Leeuwen, an epidemiologist at the Netherlands Cancer Institute in Amsterdam. A report on the findings appears in the Journal of the National Cancer Institute.
Hodgkin's disease, also known as Hodgkin's lymphoma, is a blood-related cancer that affects some 7,000 people a year in the United States, according to the Leukemia and Lymphoma Society. Treatment advances since World War II, including radiation and a variety of drug combinations, have greatly improved the odds for patients with the disease, and five-year survival rates hover around 90 percent. Still, the threat of "secondary" cancers brought on by treatment clouds the successes of Hodgkin's therapy. Although many of these secondary malignancies aren't especially serious, some can be life-threatening.
The new study made two important findings, says van Leeuwen. First, it showed that a woman's risk of breast cancer after radiation treatments for Hodgkin's disease climbed based on the dose she received. Women who got the most radiation -- at least 38.5 grays to their breast -- had 4.5 times the risk of developing breast cancer as those who got less than 4 grays. "In Hodgkin's disease treatment, the mediastinal lymph nodes are irradiated and various portions of the breast receive different doses" in the process, van Leeuwen says. "Calculating this dose was a labor-intensive part of the study, but crucial."
The chances that radiation for Hodgkin's disease would promote breast cancer dropped sharply, though not back to normal, in women whose treatment also called for chemotherapy, van Leeuwen says. Compared with women who received radiation alone, those who also underwent chemotherapy had about a 60 percent smaller risk of breast cancer, the study found. The likely reason: Chemotherapy can hasten the onset of menopause, van Leeuwen says. Since menopause is a hormone-suppressed state, and many cases of breast cancer are sparked by the female sex hormone estrogen. Inducing menopause may blunt the ability of radiation to trigger breast tumors, she says. "We already knew that radiation produces breast cancer," van Leeuwen says. "We now know with this study that with higher [doses], the risk is higher, but we now see that there is a way to substantially reduce the risk of these cancers."
A drug with an improbable molecular target has been so effective against a particularly recalcitrant form of bone marrow cancer that researchers plan to sic it on other cancers. The drug is bortezomib, which is being marketed as Velcade by Millennium Pharmaceuticals. It inhibits the activity of proteasome, a molecule essential to the activity of all cells -- so essential that many thought it would cause unacceptable damage to healthy cells as a cancer treatment. But laboratory studies, by Dr. Kenneth D. Anderson of the Dana-Farber Cancer Institute in Boston and Dr. Richard J. Ford of the M.D. Anderson Cancer Center at the University of Texas in Houston among others, showed that it could act against cells of multiple myeloma and other blood cancers without disabling side effects. A study appearing in the New England Journal of Medicine found that Velcade slowed the progress of multiple myeloma in 67 of 193 patients in whom other drugs were ineffective, with the responses lasting an average of 12 months. The response was complete or near-complete in 19 of those patients, and the average survival time was 16 months, much longer than usually seen in such cases.
"It is being tested in other cancers now," says Dr. Robert Z. Orlowski, an assistant professor of medicine and hematology/oncology at the University of North Carolina and a member of the research group. "The results are a little early, but there are encouraging results against some blood cancers, such as non-Hodgkins lymphoma, and it is being used in combination with other drugs in solid tumors."
Promising results against another hard-to-treat blood cells cancer, mantle cell lymphoma, were reported earlier this month at the American Society of Clinical Oncology's annual meeting by M.D. Anderson researchers. Of 11 patients treated with Velcade, three had complete responses, meaning that no trace of the disease could be found; four had partial responses, with the disease stabilized in the remainder. "Mantle cell lymphoma is currently nearly intractable, with a long-term survival rate of about 10 percent," says Alan Kinniburgh, vice president of research administration at the Leukemia and Lymphoma Society.
Proteasome has long been known to act as a kind of garbage disposal system of the cell, destroying damaged proteins, Kinniburgh says. Millennium Pharmaceuticals developed the drug as a treatment for muscle wasting conditions, to prevent the destruction of proteins needed for cell growth. Research showing that it could selectively stop the growth of cancer cells have led to its widening use. "Velcade works on the fundamental regulators of cell growth, which means that in addition to blood cancers, the drug has potential to treat cancers of the breast, colon and prostate," Kinniburgh says. One welcome development was last month's rapid approval of Velcade by the Food and Drug Administration, Orlowski says. The quick action is "exactly how modern medical and laboratory work should be treated," he says.
Postmenopausal women who take aspirin two or more times each week may lower their risk of developing leukemia by more than 50 percent compared with women who do not take the drug. Although these results are preliminary, this could signal yet another usage for the miracle drug that was invented more than a century ago and already has been shown to have a beneficial effect on colon cancer and heart disease. "I was very excited about the findings because leukemia is one of those cancers that has a high fatality rate," says Julie Ross, senior author of a paper appearing in the June 13 edition of Cancer Epidemiology, Biomarkers and Prevention. "If this were to hold up in other studies, we're seeing a real reduction in risk." "It certainly is a teaser in the sense that there seems to be a 50 percent reduction in the incidence of leukemia," says Alan Kinniburgh, vice president of research at the Leukemia and Lymphoma Society. He nevertheless adds that "more studies are needed to see if this holds true."
Little is known about the causes of adult leukemia, which accounts for about 5 percent of all newly diagnosed malignancies in the United States. Without information on causes, little can be done in the way of prevention. "With blood cancers, we don't really have programs to give to patients to try to avoid these diseases," Kinniburgh says. "The origin of most leukemias is unknown." The authors analyzed information on 28,244 women who participated in the Iowa Women's Health Study, which looked at overall health, lifestyle, behaviors and incidence of cancer. The women were sent a mail survey in 1992 asking them, among other things, how often they took aspirin, other NSAIDs (nonsteroidal anti-inflammatory drugs) or arthritis medicine. All of the women were cancer-free (except possibly for skin cancer) at the beginning of the study. The study authors then cross-referenced these same women with the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program, which tracks cancer diagnoses in certain areas, including Iowa.
Between 1993 and 2000, 81 women in the group had developed leukemia. Women who reported using aspirin at least two times a week had a more than 50 percent lower risk of developing leukemia compared to women who reported no aspirin use. There were other small effects depending on what drugs the respondents used, but they were not statistically significant and "the protective effect appears to be with aspirin," says Ross, an associate professor of pediatrics and a member of the University of Minnesota Cancer Center in Minneapolis. The study has several advantages. It is the first prospective study to look at aspirin use in relation to adult leukemia, meaning it looked forward rather than backward. It also compared use of aspirin to other NSAIDs.
Nevertheless, there are some limitations. For one thing, the researchers didn't know exactly how much aspirin the women were taking, or for how long. No one knows why aspirin might have a protective effect against this or any other type of cancer. "I have no idea what the mechanism might be," Ross says. "It might come down to something such as platelet aggregation. When platelets clot, growth factors are released locally. Just by reducing that activity, are you reducing overall risk?" Kinniburgh adds aspirin may have an effect on certain inflammatory processes taking place in leukemia. Ross has just submitted a grant proposal to the National Institutes of Health to conduct a large case-control study of adult leukemia and aspirin regimens.
Scientists announced that their research into the a particular type of gene therapy raises important questions about the safety of using retroviruses to carry genes into people. In gene therapy, a vector -- usually but not always a virus -- is used to carry a healthy gene into the cells of patients. If it works correctly, the virus inserts its DNA and the new gene into cells and corrects the genetic defect. Earlier this year the Food and Drug Administration halted certain gene therapy trials after two boys in France developed leukemia while they were taking part in a gene therapy trial that aimed to bolster bone marrow with genetically engineered immune cells. The treatment appeared to be working remarkably well in 10 of the group of 11 boys who had a hereditary disease that left them without an immune system.
The leukemia cases prompted researchers to speculate that the retroviral vector used in the trial may have been integrated near a known cancer-promoting gene. In the current study, lead investigator Dr. Shawn M. Burgess and colleagues analyzed where in the human genome two types of retroviruses are likely to permanently integrate. The researchers looked at one of the most commonly used retroviruses in gene therapy -- murine leukemia virus (MLV), a mouse virus that can infect human cells. And they also looked at another retrovirus -- HIV-1. "MLV was used in the French study where two children, of 11, developed leukemia," said Burgess. Burgess's team looked at 903 MLV and 379 HIV-1 integrations and found two different results for the two viruses. "This was unexpected," he said. "HIV-1 likes to integrate anywhere in genes, and MLV likes to integrate around the beginning of genes where the important regulatory sequences are," he explained. The main finding, according to Burgess, is that viruses integrate into sequences non-randomly and it appears that every virus will do this differently. "Thus, nothing about the safety of a particular retroviral treatment can be assumed," he said.
In the past the assumption was that the integrations were random and that the risk was low that the virus would integrate somewhere risky in the DNA code, noted Burgess, who is with the National Human Genome Research Institute in Bethesda, Maryland. "This is apparently not true," he said. What's more, the findings seem to jibe with what happened in the two children who developed leukemia. "The integrations that are believed to cause the problems both fit the favorite-site profile we determined for MLV," Burgess said. "Thus, the risks must be higher than we originally thought," he added. Burgess noted that the findings, which are published in the journal Science, are the first-ever documentation of a large number of integration sites for two viruses showing they behave very differently and there are inherent risks in using them for gene therapy. As such, he recommends that "any new vector should be profiled to determine the integration biases of the vector to be used to help evaluate relative risk." The new discovery may very well be a set-back for gene therapy, as there are few alternatives to using retroviruses as vectors, according to Burgess. "None of (the other types) are as far along as the retroviral vectors," he said. "They all have their own problems that are even larger than the viruses." "At the moment, (retroviral vectors) still seem the most promising, even with the associated risk," he added.
Various alphabet soups of cancer drugs are used to treat advanced Hodgkin's disease, a form of blood-related cancer that strikes the lymph system. But which combination of medicines works best hasn't been clear. A new German study helps answer the question. It found better survival rates and more remissions on a new drug regimen than on an older therapy or on a less-potent version of the new treatment. The new regimen, high doses of seven drugs known by the initials BEACOPP, had a five-year survival rate of 91 percent, several points better than the next most effective alternative. The drugs attack Hodgkin's disease in a variety of ways, from damaging DNA in cancerous cells to suppressing the formation of those cells in the first place. The regimen does have a few drawbacks: It's hard to tolerate and administer; it's costly; and, more significantly, it has a propensity to cause other blood cancers.Still, the researchers say those cancers are usually manageable and the treatment's overall effectiveness outweighs its downside.
Dr. James Armitage, a lymphoma expert and dean of the University of Nebraska's College of Medicine, calls the study "provocative." Although the researchers compared BEACOPP to a treatment, called COPP-ABVD, that's outmoded by U.S. standards, "it's higher doses of more drugs quicker and that might give an advantage." Hodgkin's disease patients in the United States typically receive the regimen ABVD-COPP. ABVD has fallen from favor after U.S. studies didn't support its use, Armitage says. So before BEACOPP becomes the standard of care here, it will have to be pitted against ABVD. "If it is better than ABVD, then I have no doubt that it will get adopted," he says. A report on the findings appears in the June 12 edition of The New England Journal of Medicine.
Hodgkin's disease, also known as Hodgkin lymphoma, is a blood-related cancer that affects some 7,000 people a year in the United States, according to the Leukemia & Lymphoma Society. Treatment advances since the 1960s have greatly improved the odds for patients with the disease, and five-year survival rates hover around 90 percent. Many patients can realistically hope to be cured of the disease.
In the latest study, Dr. Volker Diehl, of the University of Cologne, led a research team that followed 1,201 men, women and teenagers with advanced Hodgkin's disease. At the start of the study in 1993, patients were randomly given COPP-ABVD, BEACOPP or high-dose BEACOPP. By 1996, it was clear that COPP-ABVD was inferior to either of the other two treatments, so no additional patients were assigned to that group. Alan Kinniburgh, vice president for research at the Leukemia & Lymphoma Society, in White Plains, N.Y., says the study results build a strong case for using BEACOPP in patients with advanced Hodgkin's disease. But while the study is good news for most people with the cancer, some forms of the disease are more lethal than others. And in these patients, the survival rates can be quite low.
"There are some aggressive forms, and we need to find new therapies," he says. Kinniburgh's foundation is pushing for scientists to develop vaccine-based approaches to the disease. In about 30 percent of people with Hodgkin's disease, the cancerous cells are infected with Epstein-Barr virus, the microbe that causes mononucleosis. "It probably drives the growth of those malignant cells," Kinniburgh says. Other viruses may influence the course of the cancer, too, he says, so bolstering the body's defenses against these pathogens may help fight Hodgkin's disease. In an unrelated study also appearing in the same journal, European researchers say radiation after chemotherapy doesn't help Hodgkin's patients live longer or reduce their odds of the disease's return. Radiation of areas affected by cancer -- so-called "involved fields" -- does appear to improve results in patients in partial remission. Yet it does so with the price of an increased risk of other cancers, the study says. "Particularly in young patients, radiation would be something to be avoided, especially if the involved field is a lung or other major organ," Kinniburgh says.
Survivors of childhood cancer need to keep a closer watch on their hearts than previously believed, according to new research. Doctors say the harmful cardiac effects of cancer treatments may be more extensive than they realized. "It's very important for the general medical community to be aware that this population is at greater risk (for heart problems)," said study co-author Steven Lipshultz, MD, an oncologist and pediatric cardiologist at the University of Rochester Medical Center. Likewise, survivors need to be sure their doctors know their cancer treatment history so they can monitor them for heart troubles they might not otherwise look for. Lipshultz and colleagues presented the findings from two studies at last weekend's annual meeting of the American Society of Clinical Oncology.
Doctors have long known that certain types of cancer therapy - particularly treatment with drugs known as anthracyclines - can cause cardiomyopathy, a weakening of the heart muscle that can lead to congestive heart failure. But these medications are critical to treat certain cancers, so doctors generally recommend that survivors of childhood cancer who received this therapy be monitored over the long term for this particular problem. What Lipshultz and his colleagues discovered is that many survivors also show other signs of heart disease like atherosclerosis (fatty deposits in the arteries), high cholesterol, and high blood pressure. Doctors typically don't look for these conditions in this group of patients, Lipshultz said.
In one of their studies, the researchers compared three groups of people: 132 childhood cancer survivors who had received potentially heart-damaging anthracycline chemotherapy or radiation to the heart, 41 survivors who had been treated with other cancer therapies, and 59 siblings of the survivors from both groups who had never had cancer. The survivors had all received their last treatments five or more years before the study. Lipshultz said the researchers put the study groups through "every test you could think of" for heart conditions; they measured body composition, looked at hormone levels, endocrine levels, heart muscle strength, other muscular function, and more. They found that patients who had received anthracycline therapy showed an enhanced risk for accelerated atherosclerosis - something that puts them at risk of a heart attack. Even the survivors who did not have heart-damaging therapy showed signs of premature heart disease, Lipshultz said. They had a higher risk than their cancer-free siblings, though not as high as the other group of survivors. "Basically all survivors of childhood cancer should be screened at some regular set of intervals for risk of atherosclerosis," Lipshultz said. "If you find it, you can potentially intervene with preventive strategies" like diet and exercise changes, or even medication, he said.
In the second study, Lipshultz and his collaborators examined 48 people who had been successfully treated for Hodgkin disease about 15 years earlier, most when they were teenagers. Almost all of them had been treated with radiation to the chest, including the heart. None of the patients had any known heart problems, and in health and quality of life questionnaires, all said their overall health was good or better. But the researchers found that their hearts were not normal. About 60% of the patients had some type of heart valve problems - their valves were "sticky" or leaky. And more than half showed signs that the electrical impulses that control the heart's beating were slowing down. Lipshultz said some of the survivors also showed evidence of scar tissue in the main pumping chamber of the heart, and narrowing of the arteries with exercise.
"It's not just a matter of saying if you do enough tests you'll find something," Lipshultz said. "Patients who got radiation to the heart (during childhood) really need to be getting regular cardiac screening for all these types of problems." Family doctors also need to be aware of these findings, Lipshultz said, because it could affect the way they treat these patients in certain circumstances. A childhood cancer survivor who got these treatments may need to be monitored more closely during pregnancy, for instance, or when starting an exercise regimen. "If they have a heart impairment, it's important to know that because they could develop problems," Lipshultz said.
The government has approved a novel cancer treatment for one of the hardest-to-treat malignancies, rushing the drug Velcade to multiple myeloma patients in hopes it will buy them some time. Scientists hope Velcade, or similar drugs, could one day become effective for other cancers. The drug is the first anticancer proteasome inhibitor, meaning it targets an enzyme key to cell growth. Uncontrolled cell growth is cancer's hallmark. The idea: Inhibit proteasome action, and chemicals that control cell growth should be disrupted enough for cancer cells to die. Velcade maker Millennium Pharmaceuticals first tried the approach to treat multiple myeloma, a usually fatal blood cancer that strikes 14,600 Americans a year. The condition is treatable but incurable, and patients eventually run out of options. Half die within five years of diagnosis.
Velcade isn't a cure either, but studies suggest it can help a fraction of patients who have exhausted other alternatives, the Food and Drug Administration ruled. The FDA approved Velcade's sale less than four months after Millennium filed its application, under a special program that lets promising drugs for life-threatening illnesses sell before there's final proof of how well they work. Millennium gave Velcade injections to 188 patients who had relapsed despite about six prior therapies. Some 28 percent improved, and that improvement lasted a median of one year - a surprising length of time for people so sick, the FDA said. The FDA is requiring Cambridge, Mass.-based Millennium to do further research to prove if that response actually translates into living longer. But it's a response not seen with standard chemotherapy for this cancer, "so this was impressive," said Dr. Ann Farrell, who led FDA's review. Evidence so far suggests "this represents a true advance over existing therapies," added FDA oncology chief Dr. Richard Pazdur.
Normal cells contain proteasome, too, making them vulnerable to the drug. Side effects include many typical of chemotherapy: nausea, fatigue, diarrhea, constipation, headache, decreased appetite, decreased blood cell production, and a nerve damage called peripheral neuropathy. Still, for some unknown reason, Velcade, known chemically as bortezomib, appeared more likely to select myeloma cells, Farrell said. Millennium plans to begin shipping Velcade by month's end. It will cost about $20,000 per average course of treatment - 16 to 17 weeks - which is comparable to other injected cancer therapies, according to Barry Greene, the company's general manager in charge of oncology. Millennium is studying whether Velcade also could treat advanced colon and lung cancer.
A plant used in Africa to make glue and herbal remedies may be an important cause of the most common childhood cancer in Africa, scientists said on Tuesday. Children use the sap from the milkbush plant to make toys, but researchers believe exposure to the sticky liquid may make them more susceptible to the effects of a virus that causes Burkitt's lymphoma, a tumor of the immune system. "It is a critical clue to what might be driving the high frequency of Burkitt's lymphoma in Africa. It also gives us an idea of how we can begin working on preventing the cancer in the children as well," Dr. Rosemary Rochford, of the School of Public Hygiene at the University of Michigan, said in an interview.
The milkbush is common in countries like Kenya and Tanzania, where it is grown as fencing and used in medicines. Children also use it to make toys. But Rochford and her team found evidence that children may unknowingly be putting themselves in danger. When they studied the impact of the sap on the virus in the laboratory, they discovered low concentrations switched on three genes that were important in various stages of the virus, allowing it to replicate, kill cells and infect new ones. Their research is reported in the British Journal of Cancer. Burkitt's lymphoma is a very aggressive disease that has been linked to the Epstein-Barr virus. Although children are most affected by the disease, adults can also develop it. It is usually treated with chemotherapy.
Scientists had previously noticed that illness rates are higher in areas of Africa where the milkbush is more common. "Burkitt's lymphoma is found in western countries, as well as Africa, but you never see it in the jaw in western countries," Rochford explained. She suspects that while playing with the sap children might be putting their hands to the face and absorbing it into the mouth and stomach. Educating parents and children about the dangers of the milkbush could help to prevent the cancer, Rochford added. "Further research is necessary to confirm the link between exposure to milkbush sap and Burkitt's lymphoma. But this study could be important if avoiding exposure to the plant reduced the number of children suffering from the disease," said Sir Paul Nurse of the British charity Cancer Research UK.
A revolutionary gene therapy treatment that cured 10 French boys of a deadly inherited disorder known as "bubble boy disease" gave two of them leukemia, scientists said. Dr. Salima Hacien-Bey-Abina said genetic tests have confirmed that the treatment, the first time that gene therapy has cured a disease, triggered the cancer in the toddlers. The boys are responding well to anticancer therapies, she added. Experts said it is now clear that the virus used to carry the needed gene into the children's bodies landed in a bad place. Scientists had always feared that cancer might occur if the virus used in the therapy lodged near certain genes that control cell growth and affected those too.
Addressing a conference of the European Society of Human Genetics, Hacien-Bey-Abina of the Necker Hospital for Sick Children in Paris said tests have shown that in the first toddler stricken with leukemia, the correcting gene landed inside a cancer-promoting gene called LMO-2. In the second toddler, the gene landed near the LMO-2 gene. "Apart from the tragedy of those two kids, I think this has put an enormous skid under a great deal of gene therapy, on this whole business of using retrovirus vectors" to get the needed genes into the body, said Andrew Read, a professor of genetics at Manchester University and chair of the scientific committee for the conference. "That is a perfectly general problem of retroviral vectors and not a problem of the particular virus they used or the particular disease they treated and I cannot see how in principle you can get rid of that risk," said Read, who was not involved in the research.
The boys were given the treatment starting in 1999 when they were babies, ranging in age from one month to 11 months. The first toddler who developed leukemia appeared healthy until August last year - 30 months after treatment - when scientists found leukemia-like overproduction of white blood cells. After that finding, the United States suspended its three gene therapy studies for the disorder. A second child then developed leukemia in December, 34 months after getting the therapy, Hacien-Bey-Abina said. The boys were born with severe combined immunodeficiency, or SCID, a rare inherited disease that occurs in about 1 in 75,000 births. The best known victim was David, Houston's famous "bubble boy" who lived in a germ-proof plastic enclosure until his death at age 12 in 1984.
The French boys had X-linked SCID, a severe form that strikes only boys. It is the most common form of SCID, accounting for about half of cases. The disease involves a genetic mutation that leaves them without certain proteins crucial to developing disease-fighting immune cells. Without treatment, sufferers die very young. Many babies with the disorder are saved with bone marrow transplants, but they need monthly infusions of immune globulin, antibodies culled from donated blood, for the rest of their lives. To reverse the defect, doctors at Necker Hospital drew bone marrow from the boys. They mixed specific stem cells from the marrow with a harmless virus in which a gene that makes the missing protein had been inserted. They injected the reconstituted cells back into the boys, giving them a working immune system. "All the patients except patient four and patient five are doing well. They are healthy and they are at home," Hacien-Bey-Abina said. She said that one of the problems might have been the two boys who developed leukemia were the youngest in the group when they received the treatment. One was a month old, while the other was three months old. She theorized that their stem cells were possibly too immature. Also, while the average number of reconstituted cells injected back into the boys was 9 million cells per kilogram of body weight, "the two patients who developed leukemia received a particularly high number of transduced cells, around 20 million," Hacien-Bey-Abina told the audience.
Hacien-Bey-Abina proposed that one possible way around the problem is to incorporate into the virus a so-called suicide gene, which would abort the treatment if things go wrong. Another way would be to build in a buffer zone around the virus to diminish its effect on nearby genes. Even if such approaches don't work, Read said, it doesn't mean that the therapy should never be offered to children suffering from X-SCID. "In a disease like SCID, where you know the kid is going to die if you can't give them a bone marrow transplant, then if we're really talking about a one in four risk of leukemia and the leukemia is treatable, maybe the risk is worth taking," Read said. "But it's certainly not worth thinking about for more trivial conditions."
They call it the genetics of cancer, and researchers predict that one day it may lead to a cure. The approach has already hinted at a number of potentially remarkable advances, such as creating individualized -- even painless -- treatments, and finding the shared genetic characteristics between such diseases as lung, colon and breast cancer. While this may sound like science fiction, research in cancer genetics is already yielding dividends. The recent development of the highly effective leukemia drug Gleevec is considered a milestone because it targets cancer cells, while leaving healthy tissue intact and causing few side effects, oncologists note. Gleevec is used to treat chronic myeloid leukemia. However, it has spawned a new class of "targeted-therapy" drugs, and is being tested on other cancers as well, such as pediatric bone cancer. "For the first time, cancer researchers now have the necessary tools to probe the molecular anatomy of tumor cells in search of cancer-causing proteins," Dr. Richard Klausner, director of the National Cancer Institute, says of Gleevec, which was approved two years ago by the U.S. Food and Drug Administration.
The basic method of developing drugs like Gleevec is fairly simple: isolate the genetic markers of cancer to find the ones that trigger the tumor. Then test various drugs against those trigger genes to see how they react. As a possible side benefit, the data collected through the process may one day illuminate genetic links between cancers. "It may not be that all cancers can boil down to a certain gene, but it may be that certain sets of cancers, such as skin cancer, have shared characteristics," says Dr. Peter Maslak, chief of the hematology laboratory at the Memorial Sloan-Kettering Cancer Center in New York City. "There's a tremendous amount of hope that within five or 10 years we're going to understand the genetics of most cancers," adds Dr. Len Lichtenfeld, with the American Cancer Society's science department.
But with April designated as Cancer Control Month, Lichtenfeld emphasizes the best cure for cancer remains prevention. "Clearly there are a lot of new technologies and approaches, and a lot of them can help. But when we look at the big picture, what we can do right now is focus more on smoking, exercise and nutrition," he says. More than 1.3 million Americans are expected to get cancer this year, according to the American Cancer Society. Due to an aging population, the number is rising despite declines in deaths from the four main cancers -- lung, colon, breast and prostate. About two-thirds of all cancers, however, could have been prevented based on lifestyle choices, Lichtenfeld says. "There are huge returns in getting people to be healthy, stopping smoking and getting regular screenings," he says.
There have also been major advances in cancer detection. The use of molecular testing, for instance, now allows doctors to find the smallest amounts of cancer in a person's body. Although this helps doctors to monitor cancer patients in remission to ensure the disease doesn't come back, it may also help detect cancer earlier in seemingly healthy people. Traditionally, doctors had used microscopes to detect cancer cells. But this technology is inexact by today's standards, says Dr. Jerald Radich, a researcher with the Fred Hutchinson Cancer Research Center in Seattle. Using a microscope, cancer cells aren't visible unless there are lots of them -- about one tumor cell to 100 healthy cells. Molecular testing, by contrast, can find one tumor cell in a million healthy cells, leading to earlier detection and treatment, Radich says.
Many of the advances in cancer treatment result from research on leukemia. The reason is fairly simple, Radich says. Because leukemia resides in the blood, it is easier to extract and study than cancers that reside in tissue. Leukemia research gained momentum in the 1970s, while research on other cancers lagged behind, he says. But once researchers unlock the secrets of other cancer genes, a new set of questions may arise, Lichtenfeld says. For example, as targeted drugs become more refined, they may also become prohibitively expensive to develop. Lichtenfeld is also concerned that use of new therapies might outpace safety testing. A few years ago, for example, doctors thought bone marrow transplants might help women with breast cancer, but it wasn't until many of them had gone through this painful procedure that tests showed it didn't really help, he says. "Hand-in-hand with all of this wonderful technology is the question how to use it. If you don't concentrate on how to use it early on, you may have to play catch-up for many years. You don't want it used haphazardly," Lichtenfeld says.
British scientists said that early lab research suggests Prozac and similar antidepressants could treat at least one form of the cancer lymphoma. The University of Birmingham team said they had discovered that, in the test tube, the drugs could make Burkitt's lymphoma tumor cells commit suicide. Burkitt's lymphoma is a fast-growing cancer that makes up only a small percentage of all lymphomas, but is common in Africa. The drugs tested all belong to a class of anti-depressants called selective serotonin reuptake inhibitors (SSRIs). "The drugs activate the signaling mechanism that leads to the apoptosis (suicide) program. The end results is that within 24 hours the cells are dead," John Gordon, professor of immunology told Reuters Health.
Last year the same team reported that the brain chemical serotonin activates the suicide program and that SSRI drugs can block the entry of serotonin, thereby protecting cancer cells. But the latest findings, published in the American journal Blood, show that by increasing the quantity of the drug they could reverse this process, forcing the cells to commit suicide. Gordon said in a statement: "This new development is very exciting. We were intrigued as to the impact of the SSRIs on the cancer and found that by increasing the dosage of SSRIs the Burkitt's cells are killed. "The initial indicators are exceedingly positive and we are already discussing with clinicians about using these drugs as a therapy for Burkitt's lymphoma. We are now examining the effect the SSRIs have on other cancer types."
Neuropharmacologist Nicholas Barnes said the SSRIs were associated with very few side effects, even when used at high dosages. "It should therefore be possible to determine whether our research has direct clinical benefit with the minimum of delay." At present, Burkitt's lymphoma is treated with chemotherapy, which generally achieves a high cure rate. However, the scientist said response rates in the case of AIDS-related Burkitt's lymphoma are much lower. "Furthermore, the combination of chemotherapy, and the clinical support required is not always readily available in underdeveloped countries where the disease is endemic," the researcher said.
Britain's Leukemia Research Fund said: "Burkitt's lymphoma is a particularly aggressive form of cancer which affects a huge number of people in Africa and a significant number of people in the UK. "While there is still some way to go before doctors can start prescribing these drugs to patients with this cancer, these findings could be of major importance to those patients with the AIDS-related form of the disease, and to those patients who are not in a position to tolerate the intensive chemotherapy. "Alternative treatments such as this which are inexpensive and have low levels of toxicity would be a major step forward in the treatment of this disease." A spokesman for Eli Lilly, which makes Prozac, said the company was not involved in the latest research. The drug -- once the company's biggest earner -- no longer has patent protection.
British scientists have found no evidence that breastfeeding protects children against leukemia and other cancers, contradicting earlier research. Two years ago, the UK Childhood Cancer Study found what researchers called "weak evidence, of borderline statistical significance," that breastfeeding reduced childhood cancer risks. Other researchers in the United States and elsewhere have reported similar findings. But in the British Journal of Cancer, Drs. Tom Sorahan and Robert J. Lancashire from the University of Birmingham report data from more than 7,000 children in the Oxford Survey of Childhood Cancers (OSCC) that throws these earlier studies into question. "The bottom line of this report is that there was no suggestion of an association between childhood cancer risk and breastfeeding," Sorahan told Reuters Health.
The researchers used surveys of 3,376 mothers with children who died of cancer between 1972 and 1981, and compared them with the same number of mothers with healthy children. The children were matched for gender and date of birth. Their results showed no indication that breastfeeding for any length of time -- from less than one month to more than seven months -- reduced the risk of any cancer type. "In my view, this leaves the topic in limbo," Sorahan said. "The recent (UK Childhood Cancer) study has the advantage of including incident cancers, whereas my study (the OSCC) only comprised cancer deaths." However, his team's work has an advantage in its "historical" approach, Sorahan added. "I would tend to put more reliance on interview data collected many years ago," he said, "because people are now more aware of what they 'should be doing' (regarding breastfeeding), and might not be so honest with their responses."
A new Norwegian study has determined that lymph cancer cells contain special molecules which can be recognized by the immune system, the Norwegian Cancer Society reports. This property could be exploited to kill malignant cells. The study, headed by Dr. Alexander Fosså on a NCS scholarship, was carried out at the Immunology Section of the Norwegian Radium Hospital. The discovery would allow the immune system to identify the molecules and target cancer cells, making a vaccine to fight lymph cancer a distinct possibility.
"Lymph cancer patients who receive a portion of the molecules from cancer cells will have their immune systems stimulated to aggressively attack cells bearing this molecule," Fosså explained to web site www.kreft.no. Current vaccine strategies must be adapted to each patient, a time-consuming and expensive procedure. The molecules identified by Fosså differ so markedly from others in the body that they are readily identified as foreign bodies.
Gleevec has swept aside interferon-alfa combination therapy as the drug of choice for newly diagnosed chronic myeloid leukemia (CML). The results of a 16-country trial that compared the two treatments appears in The New England Journal of Medicine. The trial prompted the U.S. Food and Drug Administration (FDA) to approve Gleevec for newly diagnosed CML in December. Previously, the drug had been approved for advanced stages of CML and as a second-line treatment for earlier-stage disease, if interferon-alfa plus low-dose cytarabine, the old gold standard, failed. "We compared Gleevec to the standard of care and, by all parameters, Gleevec is better," says Dr. Hagop Kantarjian, a co-investigator on the study and chairman of the leukemia department at M.D. Anderson Cancer Center in Houston. "Gleevec is a major, major discovery.""It doesn't mean it's a complete fix, but there's no question that Gleevec is . . . better [than interferon therapy] and may well cure a whole bunch of patients," says Dr. Samuel Kopel, associate director of hematology/oncology at Maimonides Medical Center in New York City.
Currently, the only cure for CML, which affects just under 15,000 Americans, is a bone marrow transplant. But that's only an option for about 25 percent of the people who develop the disease, and it carries with it considerable risks. People with chronic CML, which is the first stage of the disease, produce too many mature white blood cells (the cells that normally fight infection). This stage progresses slowly and can last indefinitely. In the acute phase, too many immature "blasts" are produced. In a normal person, blasts give rise to a certain type of white blood cells. This acute or "blast-crisis" phase is when most patients die.
The leukocytes or cancer cells in people with CML have a genetic flaw called the Philadelphia chromosome. This irregularity produces an abnormal protein, which in turn produces a signal that pushes the cells into overdrive. "They reproduce more than they should, they live longer than they should and they suppress normal cells," Kantarjian says. Gleevec works by going inside the abnormal protein and activating it in such a way that it can no longer send these "bad" signals. "It's a very targeted kind of treatment," Kantarjian says.
Previous studies showed that Gleevec was safe and effective and led to its approval by the FDA in May 2001. What was missing was a direct comparison with existing treatments so physicians would know where to place it within the hierarchy of treatments. "The patients were telling the medical community that this it was a great therapy and that they felt much better," says Alan Kinniburgh, vice president of research at the Leukemia & Lymphoma Society. "What needed to be shown in a head-to-head comparison was if it was medically better." To that end, researchers randomly assigned 1,106 patients to receive either Gleevec (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). The study involved 177 hospitals in 16 countries. Participants were followed for a median of 19 months, and different responses to the drugs were evaluated. In the end, Gleevec appeared to rank higher in two basic and important ways: People on the drug lived longer without progressing to the next phase, and more people taking Gleevec had a reduction in the number of Philadelphia chromosomes in their blood cells. After 18 months, 87.1 percent of patients in the Gleevec group versus only 34.7 percent in the other group had a "major cytogenetic response," meaning that no more than 35 percent of the cells tested positive for the Philadelphia chromosome. The authors estimated that 76.2 percent of patients in the Gleevec group, vs. 14.5 percent of the others, had the Philadelphia chromosome completely wiped out. At the end of one year, 96.6 percent of patients in the Gleevec group had not progressed to the acute phase of the disease, compared with 79.9 percent of patients in the other group. At 18 months, 92.1 percent and 73.5 percent of the participants, respectively, had not progressed. Overall, however, the estimated survival rates were roughly equivalent -- 97.2 percent in the Gleevec arm and 95.1 percent in the combination-therapy. But that's probably because almost 90 percent of the patients in the interferon arm switched to Gleevec before the study concluded. Only 14.3 percent of the patients in the Gleevec group crossed over to interferon.
This no doubt had to do with side effects. According to Kantarjian, only 2 percent of patients on Gleevec had severe side effects, versus 30 percent or more on interferon. "It felt like night and day," says John Shaw, 42, a New York City actuary who was diagnosed with CML in 1998 and who tried interferon before joining the Gleevec trial. With an interferon combination, he adds, "I had a lot more fatigue. My concentration ability was a lot less and I didn't have as much strength as I do now. Once I went off interferon and started taking Gleevec, there was a complete difference. I feel normal again." Shaw went on Gleevec in March of 2001 and by June was in complete remission. The overall picture for people diagnosed with CML has improved drastically. "In the past when we saw patients with CML, we quoted them an average survival of three years. With interferon, that increased to about six years," Kantarjian says. "Now, with Gleevec, the average survival will go beyond 10 years and we may be able to get rid of the disease completely in at least 40 to 50 percent of patients, which in the long run is the potential for a cure," he adds.
The type of cancer that took the lives of Jacqueline Kennedy Onassis and King Hussein of Jordan may yield clues about how to train a patient's own immune system to kill malignant tumors. Ongoing research trials are targeting non-Hodgkin's lymphoma as one of the first cancers that might be treated through personalized vaccines - if they can prove a shot against cancer is effective.
Non-Hodgkin's lymphoma, a malignancy of white blood cells, is the sixth most common cancer in the United States. For mostly unknown reasons, its incidence in the United States has nearly doubled since the early 1970s, especially among the elderly. It commonly resists standard treatments such as chemotherapy.
Gleevec, a drug that showed significant results in combating a rare and mostly fatal type of leukemia, has passed another hurdle. The U.S. Food and Drug Administration has announced that Gleevec (imatinib mesylate) has been approved for the "first-line treatment of patients with chronic myeloid leukemia (CML), an uncommon life-threatening form of cancer -- affecting about 40,000 people in the United States."
First-line treatment means that Gleevec can be administered after CML has been diagnosed. The drug was originally approved in 2001 under the FDA's accelerated approval regulations.The federal agency believed more time was needed to determine whether Gleevec would continue to be as effective in arresting the leukemia as it had been when it was used after other drugs had been tried. "Today's approval represents continued efforts by government and industry to provide patients suffering from CML with additional therapies that have proven safe and effective through on-going research and clinical trials," said FDA Commissioner Dr. Mark B. McClellan. "With this new use, even more patients will have access to this product earlier on in their fight against cancer," he said in an FDA press release.
Approval was based on a clinical trial of 1,106 patients with newly diagnosed chronic phase CML, according to the FDA. Half were given Gleevec and half were given a standard drug therapy. The results: The patients treated with Gleevec after one year had significantly fewer cancerous cells in their blood and bone marrow. The rate of progression of disease was also decreased in the patients treated with Gleevec, according to the FDA.
British scientists have developed a new stem cell technique that could help patients with advanced leukemia or lymphoma. They genetically tinkered with donor stem cells -- master cells that can develop into virtually any cell type -- so that they can survive highly toxic chemotherapy. Raj Chopra, a doctor at the University of Manchester, who developed the technique, told a cancer conference that preliminary results from early animal studies were encouraging. "Our new system, which we call genetic chemoprotection, prevents donor stem cells from being harmed by chemotherapy and so should allow us to use much higher doses than would otherwise be possible," Chopra explained.
Stem cell transplants may be used to treat leukemia and lymphoma, cancers of the blood and the lymphatic system that have not responded to normal therapy. Donor stem cells are transplanted into the patient to produce an immune response against the disease. It is often followed by high-dose chemotherapy to kill the cancerous cells but the toxic drugs can also harm the donor stem cells. In an effort to overcome the problem, Chopra and his colleague Dr Lez Fairbairn isolated stem cells, grew them in the laboratory, and used a virus to insert a gene, called Atase, to make them resistant to the toxic effect of the chemotherapy drugs. In a study on mice, the chemotherapy drugs killed the cancerous cells and many of the animals' own stem cells but the transplanted donor cells survived and strengthened the animal's natural anti-cancer immune system. The immune system response increased with the proportion of donated stem cells and the transplanted cells multiplied and filled in the gaps left by the destroyed natural stem cells.
"The immune response is entirely generated by the cells we've transplanted," Chopra told a meeting of the medical charity Cancer Research UK. Although it is still very early days and human trials of the technique are still many years away, Chopra said the treatment could potentially make treatments doubly effective. Stem cells, which are derived from embryos, fetuses, umbilical cords or from a patient's own tissue, have the potential of curing diseases such as diabetes, stroke, heart disease, Alzheimer's and some types of cancer. But their use is highly controversial because the most promising stem cells are derived from human embryos.
For anemic patients with hematological malignancies, conventional therapy should be tried before using epoetin, according to new practice guidelines from the American Society of Clinical Oncology and the American Society of Hematology. Under the auspices of both societies, Dr. J. Douglas Rizzo from the Medical College of Wisconsin, Milwaukee, and colleagues developed an evidence-based guideline for using epoetin in anemic cancer patients. The guidelines are published in the Journal of Clinical Oncology.
The guideline panel recommends epoetin as a treatment option in patients with chemotherapy-related anemia whose hemoglobin level is less than 10 g/dL. In patients with less severe anemia, clinical circumstances should determine epoetin use, they add. Dr. Rizzo's group notes that evidence from clinical trials supports giving epoetin subcutaneously three times per week at doses of 150 U/kg for at least 4 weeks. They also recommend increasing the dose for patients who do not respond to initial therapy. When there is no response, treatment should not be continued beyond 6 to 8 weeks, they note. Epoetin should be titrated when hemoglobin levels reach 12 g/dL, they add. "Evidence from one randomized controlled trial supports use of epoetin for patients with anemia associated with low-risk myelodysplasia not receiving chemotherapy; however there are no published high-quality studies to support its use for anemia in other hematologic malignancies in the absence of chemotherapy," Dr. Rizzo's team comments. Dr. Rizzo and colleagues conclude that "for anemic patients with hematologic malignancies, it is recommended that physicians initiate conventional therapy and observe hematologic response before considering use of epoetin."
A new cancer-killing "cocktail" shows promise in laboratory studies as an effective way to attack acute myeloid leukemia (AML), a cancer of the blood. A team led by Dr. Edward D. Ball, director of the Blood and Marrow Transplantation Program at the University of California-San Diego School of Medicine, report the findings in the Biology of Blood and Marrow Transplantation.
The researchers took blood samples from 12 patients, either diagnosed or just relapsed with AML. They separated out the white cells, which included AML cells and T-lymphocytes, the family of cells that mount an immune response to infected or cancerous cells. To the mix, they added growth factors and interleukin-4 -- which helps activate the immune system -- to turn the lymphocytes into stronger fighters. "We induced them to change into dendritic cells, which are better able to induce immunity or immune response from T-cells," Ball says. "At the end of the 40-day culture, we had a pure culture of T-cells. Almost all the leukemia cells were gone."
The work is at the laboratory stage, Ball cautions, and he must prove the cancer cocktail works in animals and in humans before it can become available. The long-term hope, of course, is to have the cancer "cocktail" be a cure. About 10,600 new cases of AML are diagnosed each year, according to the Leukemia & Lymphoma Society. AML is also called by other names, including acute myelogenous leukemia and acute myelocytic leukemia. Patients often feel a loss of well-being and complain of fatigue. They may notice bruises after minor injuries and have fever, swollen gums, and slow healing of cuts. Currently, Ball says, "we're pretty good at getting people into remission. But over 50 percent relapse. And when they relapse, they start to develop chemotherapy resistance." Bone marrow transplant is another treatment option, he says, but even then "a fair number will relapse after transplant."
Other experts familiar with the study offer praise. "It's a very interesting lab study that may be useful as a treatment for people with AML," says Alan Kinniburgh, vice president of research for the Leukemia & Lymphoma Society. "It's very preliminary. The results need to be confirmed in another lab. And we need to see if it works in people. We'll have to wait to see whether the cells can be reintroduced successfully [back into people]." The latest study extends the possibility that immunotherapy might be effective, says Dr. Stephen Forman, director of the hemotologic neoplasia program at the City of Hope Cancer Center in Duarte, Calif. "What Dr. Ball's approach does is take a series of growth factors and stimulate them in culture to generate cells from a patient's own blood that will recognize leukemia and kill it," he says.
Men who consume moderate amounts of wine on a regular basis seem to have a reduced chance of developing non-Hodgkin's lymphoma, researchers report. However, it is not clear if the wine itself--or some other lifestyle-related factor--is responsible for the risk reduction.
Non-Hodgkin's lymphoma refers to several types of cancer that start in the lymphatic system but often spread throughout the body. It is the fifth most common cause of cancer in the US, according to the study's lead author Dr. Nathaniel C. Briggs of Meharry Medical College in Nashville, Tennessee. Although a weakened immune system and exposure to certain chemicals on the job are linked to non-Hodgkin's lymphoma, overall risk factors for the disease are "obscure," Briggs told Reuters Health. "Because so few risk factors have been identified, efforts to prevent non-Hodgkin's lymphoma need to take protective factors into consideration," added Briggs. While several studies have found that wine drinkers seem to be less likely to develop the disease, the research is inconclusive.
In a new study, Briggs and colleagues looked at 960 men between the ages of 32 and 60 who were diagnosed with non-Hodgkin's lymphoma between 1984 and 1988. They compared the men's lifestyle habits with 1,717 similarly aged men who were cancer-free. The investigators found that men who regularly drank an average of one or more glasses of wine daily, and who had been regular drinkers--averaging one or more alcoholic beverages per week from the time they were teenagers--had a more than threefold decrease in non-Hodgkin's lymphoma risk compared with nondrinkers, Briggs explained. Among wine drinkers who started drinking at older ages, the protective effect against non-Hodgkin's lymphoma was less pronounced--a 30% reduction in non-Hodgkin's lymphoma risk with consumption of one or more glass of wine daily, the researcher added. There was no link between consumption of beer or spirits and a higher or lower risk for non-Hodgkin's lymphoma, according to the report in the American Journal of Epidemiology.
Although wine drinkers in the US tend to be wealthier than those who consume other types of beverages, the researchers tried to take that into account by correcting for education. However, there may have been other factors associated with higher income--such as a healthier lifestyle in general--which could not be taken into account because the researchers did not have that information. "In no way do we endorse underage drinking," said Briggs. "In fact the absence of any protective effect for consumption of beer or spirits suggests that alcohol itself is not the protective factor."
Instead, Briggs noted that a chemical called resveratrol, which is "a phytoestrogen produced by grapes, and a natural ingredient in wine, has been shown to inhibit the initiation, as well as promotion and progression of cancer." According to Briggs, "If the association is real, non-toxic non-Hodgkin's lymphoma prevention strategies might be possible, such as resveratrol-enriched table grapes or grape jelly." Red wine has higher levels of resveratrol, but the researchers did not determine if the men drank red or white wine, or a combination of both. Briggs pointed out that the findings can't be extrapolated to consumption of more than one glass of wine per day, because there were too few heavier wine drinkers to investigate risk at higher levels. And, Briggs noted that because the study population was restricted to men, the findings may not be generalizable to women.
Novartis said that its anti-cancer drug Gleevec is receiving a priority review from the U.S. Food and Drug Administration for use by a wider range of sufferers. The FDA took only three months to approve the drug for the treatment of adults in the late-stages of chronic myeloid leukemia, or CML, and stomach cancer. Now the Swiss pharmaceutical company has applied for approval of Gleevec - known as Glivec outside the United States - for the treatment of children and of newly diagnosed CML patients. The FDA grants priority reviews to products for serious or life-threatening diseases that may offer a significant improvement compared with existing therapies. "The current labeling represents around 25 to 30 percent of patients suffering from chronic myeloid cancer," said David Epstein, head of Novartis' oncology unit. He said research and trial data show that the earlier CML patients are treated with Gleevec, the more likely they are to respond positively to the drug.
Currently, a bone marrow transplant is the only known cure for CML. The standard treatment is with interferon, which can extend a leukemia patient's life by up to two years but can have side effects that cause about 20 percent of patients to stop using it. Initial data showed that the treatment with Gleevec is about three times more effective than today's standard treatment with interferon, Epstein said. Novartis is developing a number of drugs that work similarly to treat solid tumors found in colon, ovary or breast cancer, metastatic colorectal cancer and iron overload, he said.
A new test that should allow doctors to fine-tune treatment for children with leukemia is being evaluated in Britain, researchers said. Dr. Nick Goulden, from Bristol Royal Hospital for Children, and colleagues in Glasgow, Leeds, London and Sheffield, are using "real-time quantitative polymerase chain reaction" (RQ-PRC) to measure the number of leukemia cells left after a child with acute lymphoblastic leukemia (ALL) undergoes chemotherapy. ALL is the most common form of leukemia, affecting 450 children each year in the UK, or about 75% of all cases of childhood leukemia.
Children treated for this cancer always have some leukemia cells remaining in their bone marrow after the first month of chemotherapy, Goulden said. The level can fluctuate between 1 in 20 cells to 1 in 10,000 cells, but conventional techniques cannot accurately measure the levels. Improvements in treatment for ALL over the last 30 years have raised survival rates to around 80%, but aggressive chemotherapy has unpleasant side effects that may be unnecessary for children with low numbers of residual cells, the researchers say. "Preliminary studies have demonstrated that measuring residual disease enables us to predict whether a child will relapse," Goulden said in a statement. "We hope that once this test is established in the UK, doctors will be able to intervene at an earlier stage with more or less aggressive therapy based on the level of residual disease present in the blood and bone marrow."
After the genetic sequence of a leukemia cell has been identified, RQ-PCR allows scientists to amplify the sequence millions of times within the space of a few hours. Dr. David Grant, scientific director of the Leukemia Research Fund, said: "This is a key step forward which should lead to better treatment for every single child who is diagnosed with this terrible disease."
Treating a viral infection can help some patients with a rare cancer of the immune system, French researchers say in a finding that might sound esoteric but offers a new way to fight many kinds of leukemia and lymphoma. The cancer is splenetic lymphoma, a malignant overgrowth of the white cells the body makes as a reaction to infection, and the infectious agent is hepatitis C virus.
Seven of nine patients with the lymphoma had complete remissions after they were given interferon to fight the virus. Two other patients had the same remission when ribavirin, another antiviral drug, was added to the treatment, says a report from researchers at Necker Hospital in Paris. It appears in New England Journal of Medicine. All those patients were given the antiviral drugs because they tested positive for hepatitis C. Tellingly, six patients with the same lymphoma who were not infected with hepatitis C were not helped by antiviral treatment.
Why is such a small trial interesting? Because it adds to the growing body of evidence that an infection can trigger a cancer of the immune system, says Alan J. Kinniburgh, vice president for research of the Leukemia and Lymphoma Society. "A virus elicits a response of the immune system to fight the infection, and in that process there is rapid division of white cells," Kinniburgh explains. "There may be mistakes made in replicating those cells, and some of the resulting cells have a growth advantage that continues and manifests itself as these rare lymphomas. What this study points to is that these infectious agents may be participating in other lymphoid diseases, such as chronic lymphoid leukemia."
Both lymphomas and leukemias are malignant overgrowths of white blood cells, Kinniburgh says. "If the disease occurs in the blood and not in the lymph nodes, we call it a leukemia," he says. "If it occurs in the lymph nodes, we call it a lymphoma. This one occurs in the spleen, as well as the lymph nodes." One prospect is to detect such a cancer in its early stages, he says: "If we can recognize that this process is occurring, we could use antiviral treatment to stop it. But that now is speculation. We need much more research in this area."
A role for viruses in leukemias and lymphomas was recognized as early as the 1960s, when the Epstein-Barr virus was detected in a malignancy called Burkitt's lymphoma, says an accompanying commentary by Dr. Joseph S. Pagano of the University of North Carolina at Chapel Hill. Since then, more than half a dozen viruses have been associated with different lymphomas, Pagano says, and the new report "broadens our perspective." However, the picture is complex, Pagano and Kinniburgh say. Many people are infected with the hepatitis C virus, and very few of them develop lymphoma, and not everyone with a lymphoma is infected with the virus, Kinniburgh says. In the French report, six of 15 patients did not have the infection. However, looking for signs of infection in patients with leukemia and lymphoma could lead to new treatments, Pagano writes. "A holy grail in cancer is the discovery of cellular markers that are distinct from those found in normal cells," he says. "Thus, virus-associated cancers that express viral neoantigens serve as inviting targets for specific therapeutic interventions." "Larger therapeutic trials of antiviral therapy are needed to determine the role of antiviral therapy in hepatitis C virus-infected patients with low-grade lymphoma," the French researchers write.
Genetic testing could help predict how patients with a common form of lymphoma will respond to chemotherapy, new research suggests. An international research team has identified several genetic "signatures" that are related to the odds of survival after chemotherapy among patients with diffuse large-B-cell lymphoma, the most common type of adult lymphoma. The findings suggest that genetic analysis of patients' tumors could point toward the best treatment approach, according to the study authors. For example, a patient deemed unlikely to be cured with chemotherapy might instead be offered a bone marrow transplant as a first-line treatment, Dr. Louis M. Staudt told Reuters Health.
Lymphomas are a group of related cancers of the lymphatic system, a component of the immune system that carries infection-fighting white blood cells. Because lymph nodes and other lymph tissue exist throughout the body, lymphoma can arise in or spread to a range of tissue. There are two major forms of the disease--Hodgkin's and non-Hodgkin's lymphoma--and further subgroups. Diffuse large-B-cell lymphoma accounts for roughly 40% of non-Hodgkin's lymphomas. About 2 years ago, Staudt and his colleagues used "molecular profiling" to identify two distinct forms of diffuse large-B-cell lymphoma that showed different responses to chemotherapy. In the new study, which involved tissue samples from 240 patients, the researchers found a third, distinct subgroup of the disease. Survival after chemotherapy differed among the groups, with patients with the more-favorable form having a 5-year survival rate of 60%--compared with 35% and 39% for the other two forms, the report indicates.
Moreover, the researchers found several patterns of gene expression in patients' tumors that further separated higher- from lower-risk patients within the disease subgroups. These genetic "signatures" were related to factors such as whether tumor cells were dividing rapidly and how well a patient's immune system was fighting the cancer. The team came up with 17 genes that could be used to predict survival after chemotherapy. "We feel these 17 genes...can be translated into a clinical test," Staudt said. However, genetic analysis like that used in this study cannot account for all the factors that determine a patient's treatment response, according to an editorial accompanying the report. While the study is an "an important step forward," it remains to be seen whether a predictive test based on the findings will advance the treatment of diffuse large-B-cell lymphoma, writes Dr. Ian Magrath of the International Network for Cancer Treatment and Research in Brussels, Belgium. The editorialist adds, however, that "whatever the immediate future," molecular profiling will aid in developing new, targeted cancer drugs. Already, Staudt said, the NCI is planning a trial of combining chemotherapy with a drug that specifically inhibits a molecular "pathway" called NF-kappa B that is activated in one of the subgroups of large-B-cell lymphoma that has a poor prognosis.
Women who have conquered childhood leukemia should not put off having children for too long because the cancer drugs they were given may have affected their fertility, said Danish scientists. Even though they may have normal monthly cycles, their ovaries may be producing fewer follicles and eggs, said Dr. Elisabeth Larsen of the Fertility Clinic at Copenhagen University. "The new finding is that female childhood cancer survivors with an apparently normal menstrual cycle might have a shortened reproductive span," said Larsen. Although it is not possible to estimate how much shorter the span might be, Larsen said her hospital is advising childhood leukemia survivors to have their first child before they are 30. "They should not postpone childbearing, and it might be that they should consider becoming mothers before pursuing a career," she said.
Advances in chemotherapy drugs have increased the survival of children with childhood leukemia but doctors are discovering they can produce late effects. Larsen and her team studied 26 women who had treatment for childhood leukemia and a control group of 20 healthy women. They found that the cancer survivors had shorter monthly cycles and smaller ovaries and they produced fewer follicles, which contain the egg, than the women who had never had cancer. "Although these long-term survivors of childhood leukemia have an apparently normal ovarian function, our results suggests that the chemotherapy has reduced the numbers of follicles in the ovaries," said Larsen. She suggested that childhood cancer survivors receive fertility counseling and be advised that their fertility may be reduced because of the treatments they had earlier. "The important message to come from this research is that women who have survived acute lymphoblastic leukemia can become pregnant and have babies and they are doing so," Larsen told the annual meeting of the European Society of Human Reproduction and Embryology (ESHRE) here.
Two recent studies of households in England, Scotland and Wales suggest that high levels of naturally-occurring radiation, such as radon, do not translate into a greater risk of cancer in children who live in those homes. The researchers, who published their studies in the British Journal of Cancer, said there has been some suggestion from previous studies that radon and cosmic or ground radiation might contribute to childhood cancers such as leukemia and lymphoma. But their results showed otherwise. "Although some areas have higher levels of radon or gamma radiation than others, the differences don't seem to be big enough to produce a detectable effect," said Sir Richard Doll, a professor at the University of Oxford, and chairman of the UK Childhood Cancer Study group that conducted the research.
In the first study, the scientists compared radon measurements from the bedrooms and living rooms of 2,226 children who had cancer with those from homes of 3,773 children who were healthy. Higher radon levels did not seem to play any role in promoting six different cancers, including acute lymphoblastic leukemia and other leukemias, non-Hodgkin's lymphoma, Hodgkin's disease, central nervous system tumors and other solid tumors. In fact, the researchers found that increasing radon levels were associated with lower cancer rates. But they said they aren't sure why. Not surprisingly, there were higher radon readings in wealthier homes, which tend to have double-glazed windows, central heating, and other amenities that keep houses more airtight. But the cancer rates were no higher or lower for those homes.
The authors said that even though they may not have gotten accurate average radon readings--levels vary with the season---the levels they did measure "offer no support for the suggestion that radon concentration is associated with the incidence of childhood cancer in general, or of leukemia in particular." In the second study, a detector was used to measure natural gamma ray radiation in the homes of 2,165 children with cancer and 5,086 homes of healthy children, for 5 to 7 months. Based on the results, "there is no suggestion of either an increasing or decreasing risk from any of the groups," said the authors. There has been scant suggestion that natural radiation from outer space or the ground might contribute to childhood cancer, but it has been a worry of British parents, according to Doll.
Alan Kinniburgh, vice president of research of The Leukemia & Lymphoma Society in White Plains, New York, said that it is reassuring to know that radon and background radiation may not be linked to these types of cancers, but the results are not surprising, since they are viewed as unlikely contributors. Rates of leukemia, lymphoma and brain cancer in children are very low, he said, noting that there are only about 2,400 new childhood leukemias each year in the US. The likely cause in most cases seems to be gene transcription errors, not environmental factors, he said. Radon is a naturally occurring gas that seeps into buildings from the surrounding soil. A person is unable to see or smell radon gas and the only way to know if a problem exists is to test for it. Long-term exposure is known to increase the risk of lung cancer in adults, particularly in smokers.
Dramatic results from an experiment with people suffering from a form of lymphoma are demonstrating an extended remission rate where none existed before. High-dose radioimmunotherapy (RIT) offers long-term remission for people with mantle cell lymphoma, according to research presented at the Society of Nuclear Medicine's annual meeting in Los Angeles. Mantle cell lymphoma is also known as a B-cell lymphoma, an often-fatal form of Non-Hodgkin's Lymphoma.
About 1,300 new cases occur yearly in the United States. People with mantle cell lymphoma rarely live more than three years after diagnosis. "Radioimmunotherapy is systemic radiation therapy using monoclonal antibodies tagged with radioactive isotopes that target tumor cells... radioimmunotherapy is used in treating metastatic breast cancer, B-cell lymphomas, and prostate cancer that has not responded to conventional hormone ablation therapy." The German study presented today included 12 people with mantle cell lymphoma who had relapsed after receiving high-dose chemotherapy. In the study, the people were given either low-dose rituxan (an anti-lymphoma chemotherapy drug) with RIT or a high-dose regimen of the same therapy. There was complete remission in seven of the eight patients who received the high-dose RIT, compared to only one of four people treated with low-dose RIT. The other patient who received the high-dose RIT had a partial remission. After 42 months, seven of the eight high-dose patients were still alive and six of them were in complete remission, the researchers said.
The novel cancer drug Gleevec, already used to treat advanced stages of a bone marrow cancer known as chronic myeloid leukemia, can also help prevent early stages of the disease from advancing to the deadly phase better than conventional treatment can, new research shows. "Based on this study, Gleevec should now be considered the standard first-line therapy for chronic myeloid leukemia," said study author Dr. Brian Druker of the Oregon Health and Science University in Portland. "By all parameters measured, Gleevec was significantly superior to (standard) interferon-based therapy," he said at a meeting of the American Society of Clinical. Other experts agreed. "The striking thing about this paper is that extremely few patients went on to the blast crisis phase of leukemia," said ASCO president Dr. Larry Norton, of Memorial Sloan-Kettering Cancer Center in New York. "This is actually preventing the emergence of a disease that would otherwise be much harder to treat."
The study compared the effectiveness of Gleevec, also known as STI-571, to standard drug therapy--interferon plus cytarabine--in 1,106 patients newly diagnosed with chronic myeloid leukemia. After a median follow-up of 14 months, 68% of patients treated with Gleevec showed no signs of cancer, compared with 7% of those in the interferon group, Druker reported. Gleevec was "10 times more effective," he said. And just 1.5% of patients in the Gleevec group developed the severe, deadly stages of the disease, compared with 7% of the other patients. Unlike other available cancer treatments, Gleevec is unique in that it specifically targets cancer cells, sparing healthy tissue and therefore causing fewer side effects.
The drug, made by Novartis AG, is known as a tyrosine kinase inhibitor because it interferes with an abnormal tyrosine kinase enzyme that promotes cancer growth. Gleevec has been on the market since last May, when it was approved by the US Food and Drug Administration for the treatment of advanced chronic myeloid leukemia. In the new study, fewer than 1% of Gleevec patients had severe side effects, compared with 23% of the other group. Druker said the worst adverse reaction associated with Gleevec was severe swelling, known as edema.
The number of children who survive cancer has surged dramatically in the past three decades. By one estimate, 75 percent to 80 percent of patients can now expect to live five or more years, up from only 20 percent to 25 percent 30 years ago. That statistic is one of the first major findings to be released from an unprecedented study into the long-term health of childhood cancer survivors. It was made public yesterday at the American Society of Clinical Oncology meeting in Orlando, Fla. This encouraging news means aggressive treatments pioneered in the 1970s are working, and working well. However, it also means that, while doctors know the short-term effects of the drugs used to treat young cancer patients, they have little idea what the long-term health prospects are because past survival rates were so low. "It's become so important to find out what is happening long-term with these kids so we can adjust treatment for kids still coming along," says Dr. Stuart Toledano, a professor of pediatrics and the head of pediatric oncology at the University of Miami. "If we can't prevent the disease, at least we want to give treatment that's not only effective but also the least toxic. In addition, some treatments may have unforeseen effects as a person ages."
For the Childhood Cancer Survivor Study, researchers at 25 sites nationwide gathered information from 14,000 young people who had had cancer between 1970 and 1986, before they turned 21. The study, which began nine years ago, is funded primarily by the National Cancer Institute. The study found the majority of survivors over the age of 18 considered themselves to be in good general health, with a quality of life comparable to anyone else.
However, the news isn't all good on all fronts. Female cancer survivors were found to have more problems with mental health, anxiety and physical activities. Also, survivors of brain tumors, Hodgkin's disease, bone tumors and soft tissue sarcomas seemed to be at the highest risk for health problems. There was a significantly higher occurrence of pulmonary complications, including lung fibrosis, emphysema and pneumonia, in cancer survivors. Radiation and some forms of chemotherapy are known to have short-term adverse effects on the lungs. The study confirms that damaging effects can also emerge months and years after therapy, says lead investigator Leslie L. Robison, a professor of pediatrics at the University of Minnesota Medical School.
Survivors of acute lymphoblastic leukemia were much more likely to be obese or overweight than their siblings, especially if they had received cranial radiation. Cranial radiation has been a mainstay of leukemia therapy because it prevents leukemia cells from entering the central nervous system, Robison says. The long-term health implications of obesity are, of course, considerable. "If you add that on to a patient or survivor who may have received chemotherapy, which could damage the heart, we may be setting up a population of survivors who are at an extremely high risk for cardiovascular events. If that's the case, that group needs to be followed exceedingly closely."
Bone tumor survivors, on the other hand, reported few difficulties, regardless of whether they had had a limb amputated. "At this stage, analyses are suggesting that [bone tumor] survivors don't show any difference in terms of physical function, as well as quality-of-life perception," Robison says. This information could help families and physicians when they're faced with the decision of having to amputate or undergo a different procedure that involves its own risk.
The just-released results are the tip of the iceberg. The study will continue indefinitely, while investigators research a whole spectrum of potential health drawbacks from cancer treatments, including the possibility of premature menopause and reduced fertility. Robison expects an average of 10 to 12 new scientific studies to be published every year. The findings could be critical to the well being of children who are only now being diagnosed with cancer.
Toledano tells the story of a teen-aged boy he successfully treated for Hodgkin's disease more than 10 years ago. Toledano kept in touch infrequently with the boy's mother, learning when his former patient went to college, got married and settled down with a good job. A year and a half ago, Toledano was shocked to learn the young man had died of a massive heart attack at the age of 30. The autopsy results showed he had extraordinarily severe thickening of the arteries. In retrospect, Toledano says some of the chemotherapy the boy received, as well as radiation, could have affected his heart. Now, Toledano screens all his young adult patients for lipids, or fats, and other indicators of heart disease. "You don't wait because the aging process might occur much earlier," he says. "Those things you only gain from long-term follow-up."
Hiring the immune system's hit molecules may help bone marrow transplant patients better tolerate the grafts, and even fight the cancers they're designed to treat. Leukemia patients who receive a marrow donation with the right kind of "natural killer cells," which do just what their name suggests, are much less likely to reject the grafts, according to a new studies by U.S. and Italian researchers. Experiments in mice show the natural killer cells also appear to help eradicate lingering leukemia. Better yet, targeting an enzyme that seems to arouse them may make bone marrow grafts more palatable to patients. The findings, reported in Science, could give doctors another layer of screening for bone marrow recipients to improve their chances of success.
"You can try to do these tests before you do the transplant and find not just a well-matched donor, but one whose natural killer cells will react against the patient's leukemic cells," says Alan Kinniburgh, vice president of medical affairs and research for the Leukemia and Lymphoma Society. William J. Murphy, director of basic research at SAIC, a Maryland research firm that contracts with the National Cancer Institute, says natural killer cells have only lately begun to stir interest in cancer circles. However, the cells are showing promise not only in leukemia and lymphoma, but also in certain metastatic solid tumors. "Some people are using activated killer cells as an immunotherapy without bone marrow transplant," he adds.
Currently, patients and marrow donors are matched for six immune proteins called HLA (or MHC), expressed on the surface of certain blood cells. Although five of six is considered a close match, many patients have only three or fewer of these proteins in common, and even a single mismatch can lead to devastating rejection of the transplant. To reduce the chances of rejection, doctors take pains to knock out a patient's T-cells, which help marshal an immune reaction against the foreign tissue. Yet, in doing so they make graft recipients vulnerable to graft-versus-host disease, a potentially deadly reaction that occurs when immune cells in the transplanted marrow turn on the already-weakened patient. Taken together, Kinniburgh says, the two reports suggest T-cell depletion might not be necessary if scientists pay attention to the natural killer cells of the donor and patient.
In the Italian study, a team led by Dr. Andrea Velardi of Perugia University first analyzed cell samples from 92 people with either acute myeloid (AML) or acute lymphoblastic (ALL) leukemia. All had undergone bone marrow transplants to treat their disease. The AML patients who received killer cells more antagonistic to their own tissue, based on molecular receptors they expressed, had a five-year rate of relapse 60 times lower than those with more agreeable cells, the researchers say. Velardi's group also showed that giving mice with severely suppressed immune systems a shot of killer cells wiped out traces of human leukemia with which they'd been injected. In the second study, Florida scientists showed that manipulating natural killer cells in graft recipients may also prove effective at preventing tissue rejection and treating disease. "What the Italian study is saying is that if we take NK [natural killer] cells from the donor and let them attack the host, they'll clean things out. We can do that in the host by just getting rid of one gene," says lead author William G. Kerr, of the Moffitt Cancer Center and Research Institute in Tampa.
The gene is called SHIP, and it produces an important enzyme in the immune response. However, when mice lack SHIP their natural killer cells lose their will to attack foreign tissue. Kerr says the finding could lead to drug treatments to neutralize killer cells by mollifying SHIP. In the meantime, he adds, the Italian research is farther along clinically. When they start a trial in patients, he says, "if I had [acute myeloid leukemia] I'd be signing up." Murphy, who studies killer cells, says it may also be possible to purify natural killer cells from a graft donor and use them to supplement the therapy and destroy residual leukemia. The Italian researchers had success with this approach in their work in mice, he notes. However, Kinniburgh says, scientists may "want to creep up on this a little more slowly," especially since the experiments may involve tinkering with the immune systems of severely ill patients.
In a development that could help oncologists identify which type of cancer a patient is suffering from very early in malignancy, scientists have created an electronic module that predicts the class of the disease by reading genetic information from the patient's marrow. Presenting their findings at the first ever international conference on 'Fuzzy Systems' in India, the two-member team of researchers from the Department of Computer Science in the Yonsei University of Korea said that the module can predict the cancer class in the major categories of Acute Myeloid Leukaemia and Acute Lymphoblastic Leukemia.
Although cancer detection and class discovery have been seriously investigated over the past three decades, there has been no general and perfect way to work out this problem, the computer engineers Jungwon Ryu and Sung-Bae Cho said in their presentation. This, Ryu said, was because there could be many pathways causing cancer and the disease itself was manifested in a tremendous number of varieties. In a work supported by the brain science and engineering research programme of the Korean ministry of science and technology, the duo worked upon DNA samples of patients of ALL or AML.
There are 7,129 known genes in human genome of which only a very few have information related to cancer. ''We extracted 25 genes and through our cancer predictor classified the category only with these genes,'' Ryu said. In the experimental stage, 72 patients were scanned to create a DNA microarray sample database. The DNA microarray consisted of large number of DNA molecules spotted in a systematic order on a glass slide also called a DNA chip. It is so powerful that one can investigate the gene information in a short time, because at least hundreds of genes are put on the DNA microarray to be analysed, Ryu told international delegates at the four-day conference organised by the Indian Statistical Institute. These slides were then imaged using scanner that made fluorescence measurements for each dye. The log ratio between the two intensities of each dye was used as the gene expression data.''To find out the genes that had cancer-related function, we applied seven feature selection methods already in use for data mining and pattern recognition,'' Ryu said. The innovative module meets the long-felt need for tools to efficiently analyse biological genomic information.
Efforts to treat an increasingly common blood-related cancer known as non-Hodgkins lymphoma have reached a new plateau, with a regimen combining chemotherapy and a monoclonal antibody known as rituximab. In a study appearing in the New England Journal of Medicine, a team of European doctors found that the remission rate among patients using the combined regimen was significantly higher than those using chemotherapy alone.
The study of 398 patients conducted between July 1998 and March 2000, part of a clinical trial by a European cancer coalition, found that 70 percent of patients treated with the combined regimen were alive two years later, compared to just 57 percent of patients using only chemotherapy. "The complete remission rates seen with this new combination are very encouraging and indicate a real change in the way this disease can be treated from now on," said study author Bertrand Coiffier, a hematologist affiliated with Gela, which studies adult lymphomas.
In a separate editorial, the esteemed medical journal hailed the discovery billed as "an improvement in overall survival in this increasingly common form of blood cancer" as a long-awaited advance in the treatment of the fifth most common type of cancer in the United States. Rituximab, marketed in more than 70 countries by the Swiss laboratories Roche under the brand MabThera, blocks CD-20 cell-surface protein found in mature B cells that become cancerous in patients who suffer from non-Hodgkins lymphoma, which accounts for about 40 percent of all new cases of lymphoma.
Fighting cancer by activating genes selectively into stem cells is possible, researchers at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins have established. The Science Daily quoted Linzhao Cheng, Ph.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center and director of the study, as saying, "Blood stem cells represent an important target for the treatment of a variety of blood and immune disorders, so our ability to engineer them to selectively stimulate immune responses opens up new possibilities for gene therapy." Using a gene known to produce a fluorescent protein, scientists transferred it into human adult and cord blood stem cells and injected the cells into immune-compromised mice. The gene transfer into the stem cells was accomplished via a lentivirus, genetically engineered to be safe, with coded instructions for the gene to turn on in a specific type of cell.
Since blood stem cells differentiate and develop into all blood and immune system cells, all descendants of the stem cells had the fluorescent protein gene. However, the gene turns on only when the stem cell developed into one type of immune cell, called an antigen-presenting cell (APC). APCs play a central role in controlling immune system responses. Cheng says this is an important step in providing a new way to achieve targeted gene therap. Six mice were transplanted with the fluorescent gene made specific for APCs. After 10 weeks, all produced the fluorescent protein in an average of 56 percent of the transplanted cells, and exclusively in APCs. Five control mice were transplanted with the fluorescent gene made universal for all cells and produced fluorescence in all types of the transplanted cells.Four additional control mice without the fluorescent gene showed no fluorescent protein in any transplanted cells. The researchers will conduct further studies to explore the possibility of delivering genes that boost the immune system to develop stronger therapeutic cancer vaccines. Other possible applications of the technology may be used to suppress the immune system to reduce adult cell transplant rejection.
Taking folic acid and iron supplements during pregnancy may help to reduce the risk of childhood leukaemia, Australian researchers said. Acute lymphoblastic leukaemia (ALL) is the most common cancer in children in developed countries, but scientists at the Cancer Foundation of Western Australia in West Perth found that folic acid, or folate, and iron were a winning combination against the disease. In a study to determine risk factors for the cancer, they found that women who took the supplements while pregnant had a 60 per cent reduced risk of having a child with the disease. Iron pills alone cut the risk by 25 per cent. Only one mother took folate without iron.
"Our results, though unexpected, suggest that folate supplementation in pregnancy reduces the risk of common acute lymphoblastic leukemia in the child," Dr Judith Thompson said in a study published in the Lancet medical journal. Childhood cancer affects about one in 600 children and leukemia accounts for about one-third of all cases. Thanks to improvements in chemotherapy in recent decades more than 80 percent of children with the cancer beat the disease. Thompson and her team studied risk factors for all cases of the illness in children up to 14 years old in Western Australia between 1984 and 1992.
"We recorded an unexpected significant inverse association between maternal use of iron or folate supplements in pregnancy and common ALL (acute lymphoblastic leukemia) in children," said Thompson. Studies have shown that folic acid supplements can also reduce the risk of neural tube birth defects such as spina bifida, a leading cause of childhood paralysis. Folic acid helps the body form red blood cells and aids in the formation of genetic material within every cell in the body. The U.S. RDA (recommended daily allowance) for folic acid is 400 micrograms per day. The biggest sources are vegetables, grain products, nuts and soy. Many ready-to-eat cereals are fortified with folic acid.
The Ministry of Health has fast tracked the registration of a new drug, which is being seen as a new generation of treatment for cancer. The drug, known as Glivec, is designed to treat people with a specific form of chronic myeloid leukaemia. Seven New Zealanders have been involved in an international trial of the drug, which researchers say has shown spectacular success. The drug company Novartis says Glivec targets the enzyme that causes cancer cells to grow and is extremely precise because it leaves the healthy cells intact. Glivec has been granted approval by the Ministry of Health in roughly half the normal time for drug assessment. The drug has already been granted similar approval in the United States, Europe and Australia.