Expert Point of View: High-dose Methotrexate Improves Outcome for High-risk Acute Lymphoblastic Leukemia in Younger Patients

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Martin Tallman, MDThe acute lymphoblastic leukemia study presented by Eric Larsen, MD, during the 2011 ASCO Plenary Session “was designed to test intensified CNS-directed therapy during the interim maintenance phase of treatment. CNS control is an important issue. Although CNS involvement occurs in less than 10% of cases, CNS relapse has increased while bone marrow relapse has decreased,” said Martin Tallman, MD, Chief of the Leukemia Service at Memorial Sloan-Kettering Cancer Center in New York and formal discussant of the trial. “The study found fewer marrow relapses and fewer isolated CNS relapses with high-dose methotrexate.”

Childhood ALL represents one of the great triumphs in oncology, with very high cure rates, Dr. Tallman continued. The present study showed a 7% difference in 5-year event-free survival favoring high-dose methotrexate, “demonstrating that we can improve survival in this disease even further,” he commented. “High-dose methotrexate should be a new standard of care for childhood ALL.”

Issues for future study include elucidating the mechanism of methotrexate resistance, study of “pediatric-inspired” therapies for adult ALL (which has much lower cure rates), and de-escalation of methotrexate doses.

Dr. Tallman cited lessons from this trial that could be applied to adults with ALL. These include the importance of sequential trials in improving outcomes and the importance of accrual of all patients with an uncommon disease to clinical trials. The study also showed that improvement in outcomes can occur without new agents, but with different uses of older ones. ■

Financial Disclosure: Dr. Tallman reported no potential conflicts of interest.

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