Novel multiagent chemotherapy for bone marrow relapse of pediatric acute lymphoblastic leukemia

Background Despite improvements in the treatment of pediatric acute lymphob lastic leukemia, approximately one in five patients will develop recurrent disease. The majority of these patients do not survive. This limited instit ution study sought to improve event-free survival (EFS) by intensification of chemotherapy. Procedure. Twenty-one patients with either an isolated mar row (n = 16) or a combined marrow and central nervous system relapse (n = 5 ) received treatment according to Children's Hospital of Philadelphia proto col CHP-540. Six patients had an initial remission of <36 months, and five patients had relapsed within 1 year of completion of phase III therapy. Ind uction and reinduction therapy consisted of idarubicin, vincristine, dexame thasone, asparaginase, and triple intrathecal chemotherapy. Consolidation a nd reconsolidation therapy employed high-dose cytarabine, etoposide, and as paraginase given in a sequential manner. Maintenance therapy included cours es of high- or low-dose cytarabine followed by sequential etoposide and asp araginase pulse, moderate-dose methotrexate with delayed leukovorin rescue, and vincristine/dexamethasone pulses. Therapy continued for 2 years from t he start of interim maintenance in the 16 patients who did not receive a bo ne marrow transplant (BMT). Two patients underwent an HLA-identical sibling BMT specified by protocol. Four received a nonprotocol-prescribed alternat ive donor BMT. Results, The complete remission induction rate was 95%. With a median follow-up from date of relapse of 49 months in survivors, the act uarial EFS based on intent to treat is 75%. There were three toxic deaths i n patients in CR and two deaths from relapse. Conclusions. This regimen is toxic but effective and deserves study in a larger setting. (C) 2000 Wiley- Liss, Inc.