PURPOSE: To improve prognosis in children with acute myeloid leukemia (AML) by randomized comparisons of (1) two short consolidation cycles versus the Berlin-Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the prophylactic administration of granulocyte colony-stimulating factor (G-CSF) versus no G-CSF. Further, therapy for standard risk patients was intensified by addition of a second induction, HAM (high-dose cytarabine and mitoxantrone). PATIENTS AND METHODS: Four hundred seventy-three patients younger than 18 years with de novo AML were enrolled in trial AML-BFM 98. Patients received five courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance therapy. RESULTS: Four hundred eighteen patients (88%) achieved remission. Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P = .005), and 5-year overall survival increased from 58% to 62% (log-rank P = .03). Both types of consolidation therapy led to similar outcome (event-free survival, 51% v 50%), but in the two-cycle arm, treatment duration was shorter (median duration, 15 days), and treatment related mortality was lower (five v nine patients). G-CSF shortened neutropenia, but did not reduce the rate of severe infections. Intensification of induction therapy did not improve prognosis of standard-risk patients (event-free survival, 62% v 67%). CONCLUSION: Overall results were improved by neither the administration of G-CSF nor by cycle therapy; however, the latter was easier to perform. Compared with study AML-BFM 93, therapy intensification with HAM in standard-risk patients did not result in improved prognosis. Future treatment designs have to balance intensification of treatment with higher toxicity, improve supportive care, and to consider alternative treatment strategies.
RCT Entities:
PURPOSE: To improve prognosis in children with acute myeloid leukemia (AML) by randomized comparisons of (1) two short consolidation cycles versus the Berlin-Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the prophylactic administration of granulocyte colony-stimulating factor (G-CSF) versus no G-CSF. Further, therapy for standard risk patients was intensified by addition of a second induction, HAM (high-dose cytarabine and mitoxantrone). PATIENTS AND METHODS: Four hundred seventy-three patients younger than 18 years with de novo AML were enrolled in trial AML-BFM 98. Patients received five courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance therapy. RESULTS: Four hundred eighteen patients (88%) achieved remission. Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P = .005), and 5-year overall survival increased from 58% to 62% (log-rank P = .03). Both types of consolidation therapy led to similar outcome (event-free survival, 51% v 50%), but in the two-cycle arm, treatment duration was shorter (median duration, 15 days), and treatment related mortality was lower (five v nine patients). G-CSF shortened neutropenia, but did not reduce the rate of severe infections. Intensification of induction therapy did not improve prognosis of standard-risk patients (event-free survival, 62% v 67%). CONCLUSION: Overall results were improved by neither the administration of G-CSF nor by cycle therapy; however, the latter was easier to perform. Compared with study AML-BFM 93, therapy intensification with HAM in standard-risk patients did not result in improved prognosis. Future treatment designs have to balance intensification of treatment with higher toxicity, improve supportive care, and to consider alternative treatment strategies.
Authors: Jeffrey E Rubnitz; Hiroto Inaba; Gary Dahl; Raul C Ribeiro; W Paul Bowman; Jeffrey Taub; Stanley Pounds; Bassem I Razzouk; Norman J Lacayo; Xueyuan Cao; Soheil Meshinchi; Barbara Degar; Gladstone Airewele; Susana C Raimondi; Mihaela Onciu; Elaine Coustan-Smith; James R Downing; Wing Leung; Ching-Hon Pui; Dario Campana Journal: Lancet Oncol Date: 2010-05-05 Impact factor: 41.316
Authors: Jan-Henning Klusmann; Dirk Reinhardt; Martin Zimmermann; Bernhard Kremens; Josef Vormoor; Michael Dworzak; Ursula Creutzig; Thomas Klingebiel Journal: Haematologica Date: 2011-09-20 Impact factor: 9.941
Authors: Hiroto Inaba; Clinton F Stewart; Kristine R Crews; Shengping Yang; Stanley Pounds; Ching-Hon Pui; Jeffrey E Rubnitz; Bassem I Razzouk; Raul C Ribeiro Journal: Cancer Date: 2010-01-01 Impact factor: 6.860
Authors: John T Horan; Todd A Alonzo; Gary H Lyman; Robert B Gerbing; Beverly J Lange; Yaddanapudi Ravindranath; David Becton; Franklin O Smith; William G Woods Journal: J Clin Oncol Date: 2008-10-27 Impact factor: 44.544
Authors: J E Rubnitz; K R Crews; S Pounds; S Yang; D Campana; V V Gandhi; S C Raimondi; J R Downing; B I Razzouk; C-H Pui; R C Ribeiro Journal: Leukemia Date: 2009-02-26 Impact factor: 11.528