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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

2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 14 Linguagem: Inglês

10.1200/jco.2009.25.1983

1527-7755

Gesche Tallen, Richard Ratei, Georg Mann, Gertjan J.L. Kaspers, Felix Niggli, A. I. Karachunsky, Wolfram Ebell, Gabriele Escherich, Martin Schrappe, Thomas Klingebiel, Ruediger Fengler, Günter Henze, Arend von Stackelberg,

Lymphoma Diagnosis and Treatment

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, population-based 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 (pEFS A = .17 ± .03; pEFS B = .43 ± .04; pEFS C = .54 ± .06; pEFS PPG = .15 ± .03; log-rank P < .001). Patients of high-risk groups A plus PPG did better with SCT than with chemotherapy (pEFS = .33 ± .05 v 0.20 ± .05; P = .005). The pEFS was similar to trials ALL-REZ BFM 85/87 (.36 ± .03. v 0.37 ± .03; P = .419; PPG excluded). Time point, site of relapse, immunophenotype, and SCT were significant predictors of pEFS in multivariate analyses. Conclusion More than one third of patients in this large, population-based trial were cured. Neither R3 nor adaptation of chemotherapy intensity was capable of improving pEFS or of overcoming prognostic factors. In high-risk patients, remission induction regimens must be improved, and allogeneic SCT should be recommended in patients achieving second complete remission.