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Treatment Option Overview

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Subgroups of patients who have a poor prognosis with current risk-adapted, multiagent chemotherapy regimens may require different therapeutic approaches. For example, infants with ALL are at much higher risk for treatment failure than older children.[13,14] Infants with ALL are generally treated on separate protocols using more intensified regimens, although the likelihood of long-term EFS appears to be no better than 50% for infants with MLL translocations even with a more intensive therapeutic approach.[13,14,15,16] Infants with MLL translocations and other subsets of patients who have a less than 50% chance of long-term remission with current therapies (such as patients with hypodiploidy or with initial induction failure) are sometimes considered candidates for allogeneic stem cell transplantation in first remission.[15,17,18,19] However, because of small numbers, possible patient selection bias, and center preference, studies to definitively show whether CR1 transplantation is superior to intensive chemotherapy for these very high-risk patients have not been feasible.

Allogeneic bone marrow transplantation was once considered to be the treatment of choice for children with t(9;22) Philadelphia chromosome-positive (Ph+) ALL, especially those with high-risk clinical features (age >10 years or high initial leukocyte count) or poor early treatment response.[20,21] However, a COG study demonstrated a 3-year EFS rate of 80.5% in Ph+ patients treated with concurrent intensive chemotherapy and a tyrosine kinase inhibitor (imatinib) given daily during premaintenance therapy.[22] While longer follow-up is necessary to determine if this treatment regimen indeed improves cure rates or merely prolongs the duration of disease-free survival, these results suggest that the presence of the Philadelphia chromosome should no longer be considered an absolute indication for transplantation in first remission.

Treatment of Sanctuary Sites (Central Nervous System, Testes)

Successful treatment of children with ALL requires the control of systemic disease (e.g., marrow, liver and spleen, lymph nodes), as well as the prevention or treatment of extramedullary disease, particularly in the central nervous system (CNS). Approximately 3% of patients have detectable CNS involvement by conventional criteria at diagnosis (cerebrospinal fluid specimen with ?5 WBC/?L with lymphoblasts and/or the presence of cranial nerve palsies). However, unless specific therapy is directed toward the CNS, the majority of children will eventually develop overt CNS leukemia. Therefore, all children with ALL should receive systemic combination chemotherapy together with some form of CNS prophylaxis. Therapies that may be used for CNS prophylaxis include intrathecal chemotherapy and cranial radiation. CNS-penetrant systemic chemotherapy (such as intravenous methotrexate and high-dose cytarabine) and other drugs, including dexamethasone and asparaginase, may contribute to CNS prophylaxis as well. At present, most newly diagnosed children with ALL are treated without cranial radiation; many groups administer cranial radiation only to those patients considered to be at highest risk for subsequent CNS relapse, such as those with documented CNS leukemia at diagnosis (as defined above) (>5 WBC/?L with blasts; CNS3) and/or T-cell phenotype with high presenting WBC count.[23] Ongoing trials seek to determine if radiation can be eliminated from the treatment of all children with ALL without compromising survival or leading to increased rate of toxicities from upfront and salvage therapies.[7,8]

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WebMD Public Information from the National Cancer Institute

Last Updated: May 16, 2012
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.

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