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Acute Lymphoblastic Leukemia: Pediatric Regimens for Adolescents and Young Adults Yield Survival AdvantagesBy Don Norwood
One of the biggest successes in cancer treatment over the past 3 decades has been a drastic improvement in overall 5-year survival rates in children and middle-aged and older adults with acute lymphoblastic leukemia (ALL). In children in particular, the rates have increased from about 20% to about 80% over this time frame—encouraging news indeed for patients with ALL diagnosed at 15 years of age or younger. The news for adolescents and young adults diagnosed with ALL is not so good, however. Unlike in children and older adults, ALL survival rates in adolescents and young adults have remained essentially unchanged since the 1970s. A treatment breakthrough for this patient group is greatly needed. Researchers at M. D. Anderson in the Department of Leukemia and the Children’s Cancer Hospital may be well on the way to such a breakthrough with their ongoing phase II study of augmented Berlin-Frankfurt-Munster (BFM) therapy. Augmented BFM is a regimen of 6-mercaptopurine, 6-thioguanine, cyclophosphamide, cytarabine, daunorubicin, dexamethasone, doxorubicin, methotrexate, polyethylene glycol-conjugated L-asparaginase, prednisone, and vincristine designed specifically for pediatric patients. In the M. D. Anderson study of augmented BFM therapy, the regimen is administered to patients 12–40 years old with Philadelphia chromosome–negative precursor B-cell or T-cell ALL or lymphoblastic lymphoma. Thus far, the results of treatment with augmented BFM have been comparable with the promising results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), a regimen designed for adults and the most common regimen for adult ALL patients at M. D. Anderson. However, augmented BFM for adolescents and young adults with ALL has proven to be advantageous over hyper-CVAD in several areas. “I think the success of augmented BFM is mainly due to differences in the delivery of the chemotherapy,” said Deborah A. Thomas, M.D., an associate professor in the Department of Leukemia. “With hyper-CVAD, the patients get the chemotherapy in a confined period of time over 3–5 days in the hospital. The augmented BFM regimen is a sequential therapy regimen, which means that different chemotherapy agents are administered at different time points throughout a cycle.” In addition, the augmented BFM therapy is given mostly in the outpatient setting, and the regimen seems to be less myelosuppressive, so fewer transfusions are required. The medications are still given intravenously, so a central line is required, and the overall duration of therapy for the two regimens is similar. Ongoing debate Whether a pediatric or adult regimen should be used to treat ALL in adolescents and young adults has been an ongoing debate for several years at M. D. Anderson and other cancer research institutions around the world. Whereas M. D. Anderson researchers have found that both hyper-CVAD and pediatric regimens have been rather successful against this disease in adolescents and young adults, most studies comparing pediatric and conventional adult regimens for ALL have found the former to be much more effective in adolescents and young adults. Specifically, the results of several trials have shown that pediatric regimens produce higher survival rates in adolescent and young adult patients. “So far, it does look like 16- to 21-year-olds do better on pediatric-type programs,” said Michael E. Rytting, M.D., an associate professor in the Children’s Cancer Hospital. “There are many reasons for that. ALL is a rare disease in adults, but it is the most common cancer diagnosis in pediatric patients. All pediatric hematologists and oncologists are pretty well informed and up to speed on ALL. So being familiar with the treatment regimen and disease gives us an advantage in treating adolescents and young adults.”
Dr. Thomas elaborated on the results of the studies comparing pediatric and adult regimens, pointing out that researchers performing a multinational trial involving ALL patients who are 16–21 years old have reported an event-free survival rate of 60%–70% for a pediatric regimen and a rate of about 40% for an adult regimen. Dr. Thomas argues that such results, which multiple studies have corroborated, mean that oncologists should choose pediatric regimens such as augmented BFM over adult regimens for ALL in adolescents and young adults. She also offers another reason why pediatric regimens are more desirable for adolescents and young adults: they are much more dose-intense (for certain nonmyelosuppressive drugs) than adult regimens are. Physician’s role Although the augmented BFM and hyper-CVAD regimens both have been effective against ALL in adolescent and young adult patients at M. D. Anderson, a proactive approach by the patient’s family physician is required for these and all other chemotherapy regimens to be effective. Dr. Rytting said that this approach includes having a healthy suspicion of leukemia, referring the patient to the proper treatment facility, and providing appropriate follow-up care. “Newly diagnosed leukemia patients ideally should be seen at a large cancer center, where the diagnosis can be confirmed and a treatment plan put into place,” said Dr. Rytting. “If they achieve remission, which requires about 4 weeks of treatment, they frequently can return to their local oncologists for the less intensive parts of their care.” Referral to large cancer centers is doubly advantageous for patients with ALL and other acute leukemias. Because patients are often quite ill when these leukemias are diagnosed, they receive rapid admittance upon referral to M. D. Anderson. “When leukemia is suspected, patients are evaluated upon referral; there’s not a waiting time,” said Dr. Rytting. “They can come to the emergency room, because it is an emergency. For pediatric patients, we try to get them seen in our clinic or admitted to the hospital the day of the referral.” The same process of rapid acceptance applies for adolescents, young adults, and older adults referred to the Department of Leukemia.For more information, contact Dr. Thomas at 713-745-4616 or Dr. Rytting at 713-792-4855. Other articles in OncoLog, February 2009 issue:
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