Intensive alternating drug pairs for treatment of high-risk childhood acute lymphoblastic leukemia. A pediatric oncology group pilot study

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Abstract
Background. To prevent drug resistance, the authors designed a protocol that featured early intensive rotating drug pairs as part of the therapy for acute lymphoblastic leukemia (ALL). Methods. After prednisone, vincristine, asparaginase, and daunorubicin induction, 12 intensive treatments (ABACABACABAC) were given in 30 weeks: A—intermediate-dose methotrexate (IDMTX) plus intermediate-dose mercaptopurine (MP); B—cytosine arabinoside (AC) plus daunorubicin (DNR); C—AC plus teniposide (VM-26). Triple intrathecal chemotherapy (AC, MTX, and hydrocortisone) was given for central nervous system (CNS) prophylaxis. Continuation therapy consisted of weekly MTX and daily MP until 2.5 years of continuous complete remission had been achieved. Results. Seventy-four children (age range, 1–19 years) at high risk of relapse were treated. Of 55 with B-lineage (early pre-B, pre-B) ALL, 24 have failed (2 induction failures, 2 deaths from infection, and 20 relapses). The event-free survival (EFS) rate at 4 years was 55.5% (standard error [SE] ± 7.7%). Of 19 patients with T-cell ALL, 12 have failed (2 induction failures and 10 relapses). The EFS rate at 4 years was 32.6% (SE ± 26.8%). Toxicities were significantly more common after AC and DNR or AC and VM-26 than IDMTX and MP. There were no toxicity-related deaths during intensive treatments. Conclusion. Early intensive rotating therapy is tolerable and warrants consideration for additional trials of patients with high-risk, B-lineage ALL.