BACKGROUND:Children with high-risk acute lymphoblastic leukemia (ALL) who have a slow response to initial chemotherapy (more than 25 percent blasts in the bone marrow on day 7) have a poor outcome despite intensive therapy. We conducted a randomized trial in which such patients were treated with either an augmented intensive regimen of post-induction chemotherapy or a standard regimen of intensive post-induction chemotherapy. METHODS:Between January 1991 and June 1995, 311 children with newly diagnosed ALL who were either 1 to 9 years of age with white-cell counts of at least 50,000 per cubic millimeter or 10 years of age or older, had a slow response to initial therapy, and entered remission at the end of induction chemotherapy were randomly assigned to receive standard therapy (156 children) or augmented therapy (155). Those with lymphomatous features were excluded. Event-free survival and overall survival were assessed from the end of induction treatment. RESULTS: The outcome at five years was significantly better in the augmented-therapy group than in the standard-therapy group (Kaplan-Meier estimate of event-free survival [+/-SD]: 75.0+/-3.8 vs. 55.0+/-4.5 percent, P<0.001; overall survival: 78.4+/-3.7 vs. 66.7+/-4.2 percent, P=0.02). The difference between treatments was most pronounced among patients one to nine years of age, all of whom had white-cell counts of at least 50,000 per cubic millimeter (P<0.001). Risk factors for an adverse event in the entire cohort included a white-cell count of 200,000 per cubic millimeter or higher (P=0.004), race other than black or white (P<0.001), and the presence of a t(9;22) translocation (P=0.007). The toxic effects of augmented therapy were considerable but manageable. CONCLUSIONS: Augmented post-induction chemotherapy results in an excellent outcome for most patients with high-risk ALL and a slow response to initial therapy.
RCT Entities:
BACKGROUND:Children with high-risk acute lymphoblastic leukemia (ALL) who have a slow response to initial chemotherapy (more than 25 percent blasts in the bone marrow on day 7) have a poor outcome despite intensive therapy. We conducted a randomized trial in which such patients were treated with either an augmented intensive regimen of post-induction chemotherapy or a standard regimen of intensive post-induction chemotherapy. METHODS: Between January 1991 and June 1995, 311 children with newly diagnosed ALL who were either 1 to 9 years of age with white-cell counts of at least 50,000 per cubic millimeter or 10 years of age or older, had a slow response to initial therapy, and entered remission at the end of induction chemotherapy were randomly assigned to receive standard therapy (156 children) or augmented therapy (155). Those with lymphomatous features were excluded. Event-free survival and overall survival were assessed from the end of induction treatment. RESULTS: The outcome at five years was significantly better in the augmented-therapy group than in the standard-therapy group (Kaplan-Meier estimate of event-free survival [+/-SD]: 75.0+/-3.8 vs. 55.0+/-4.5 percent, P<0.001; overall survival: 78.4+/-3.7 vs. 66.7+/-4.2 percent, P=0.02). The difference between treatments was most pronounced among patients one to nine years of age, all of whom had white-cell counts of at least 50,000 per cubic millimeter (P<0.001). Risk factors for an adverse event in the entire cohort included a white-cell count of 200,000 per cubic millimeter or higher (P=0.004), race other than black or white (P<0.001), and the presence of a t(9;22) translocation (P=0.007). The toxic effects of augmented therapy were considerable but manageable. CONCLUSIONS: Augmented post-induction chemotherapy results in an excellent outcome for most patients with high-risk ALL and a slow response to initial therapy.
Authors: Jose Claudio C Rocha; Cheng Cheng; Wei Liu; Shinji Kishi; Soma Das; Edwin H Cook; John T Sandlund; Jeffrey Rubnitz; Raul Ribeiro; Dario Campana; Ching-Hon Pui; William E Evans; Mary V Relling Journal: Blood Date: 2005-02-15 Impact factor: 22.113
Authors: Stephen P Hunger; Mignon L Loh; James A Whitlock; Naomi J Winick; William L Carroll; Meenakshi Devidas; Elizabeth A Raetz Journal: Pediatr Blood Cancer Date: 2012-12-19 Impact factor: 3.167
Authors: Michael J Borowitz; Meenakshi Devidas; Stephen P Hunger; W Paul Bowman; Andrew J Carroll; William L Carroll; Stephen Linda; Paul L Martin; D Jeanette Pullen; David Viswanatha; Cheryl L Willman; Naomi Winick; Bruce M Camitta Journal: Blood Date: 2008-04-03 Impact factor: 22.113
Authors: Farhad Ravandi; Jeffrey L Jorgensen; Susan M O'Brien; Elias Jabbour; Deborah A Thomas; Gautam Borthakur; Rebecca Garris; Xuelin Huang; Guillermo Garcia-Manero; Jan A Burger; Alessandra Ferrajoli; William Wierda; Tapan Kadia; Nitin Jain; Sa A Wang; Sergei Konoplev; Partow Kebriaei; Richard E Champlin; Deborah McCue; Zeev Estrov; Jorge E Cortes; Hagop M Kantarjian Journal: Br J Haematol Date: 2015-10-22 Impact factor: 6.998