Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: Results of trial ALL-REZ BFM 90

Abstract

Purpose: The multicenter trial ALL-REZ BFM (ie, Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster) 90 was designed to improve prognosis for children with relapsed acute lymphoblastic leukemia (ALL) by time-to-relapse - and site-of-relapse - adapted stratification and by introduction of novel chemotherapy elements and to evaluate new prognostic parameters in a large, populationbased cohort. Patients and Methods: Five hundred twenty-five patients stratified into risk groups A (early bone marrow [BM] relapses), B (late BM relapses), and C (isolated extramedullary relapses) received alternating short-course intensive polychemotherapy (in blocks R1, R2, or R3) and cranial/craniospinal irradiation followed by maintenance therapy. Block R3 (high-dose cytarabine and etoposide) was introduced to improve the outcome compared with historical controls. Patients with early BM or T-ALL relapse (poor prognosis group [PPG]) were eligible for experimental regimens. One hundred seventeen patients received stem-cell transplantation (SCT). Results: The probabilities (and standard deviations) of event-free survival (pEFS) and overall survival (pOS) at 10 years were 0.30 ± .02 and 0.36 ± .02, respectively. Significant differences existed between strategic groups (pEFSA = .17 ± .03; pEFSB = .43 ± .04; pEFSC = .54 ± .06; pEFSPPG = .15 ± .03; log-rank P