High-Dose Cytarabine Consolidation With or Without Additional Amsacrine and Mitoxantrone in Acute Myeloid Leukemia: Results of the Prospective Randomized AML2003 Trial

Autoři	SCHAICH Markus PARMENTIER Stefani KRAMER Michael ILLMER Thomas STÖLZER Friedrich RÖLLIG Christoph THIEDE Christian HÄNEL Mathias SCHÄFER ECKART Kerstin AULITZKY Walter EINSELE Hermann HO Anthony D. SERVE Hubert BERDEL Wolfgang E. MAYER Jiří SCHMITZ Norbert KRAUSE Stefan N. NEUBAUER Andreas BALDUS Claudia D. SCHETELIG Johannes BORNHÄUSER Martin EHNINGER Gerhard
Rok publikování	2013
Druh	Článek v odborném periodiku
Časopis / Zdroj	Journal of Clinical Oncology
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
Doi	http://dx.doi.org/10.1200/JCO.2012.46.4743
Obor	Onkologie a hematologie
Klíčová slova	STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; MATCHED UNRELATED DONORS; POSTREMISSION THERAPY; 1ST REMISSION; RESIDUAL DISEASE; YOUNGER ADULTS; CHEMOTHERAPY; AML; RECOMMENDATIONS
Popis	Purpose: To assess the treatment outcome benefit of multiagent consolidation in young adults with acute myeloid leukemia (AML) in a prospective, randomized, multicenter trial. Patients and Methods: Between December 2003 and November 2009, 1,179 patients (median age, 48 years; range, 16 to 60 years) with untreated AML were randomly assigned at diagnosis to receive either standard high-dose cytarabine consolidation with three cycles of 18 g/m(2) (3x HD-AraC) or multiagent consolidation with two cycles of mitoxantrone (30 mg/m(2)) plus cytarabine (12 g/m(2)) and one cycle of amsacrine (500 mg/m(2)) plus cytarabine (10 g/m(2); MAC/MAMAC/MAC). Allogeneic and autologous hematopoietic stem-cell transplantations were performed in a risk-adapted and priority-based manner. Results: After double induction therapy using a 3 + 7 regimen including standard-dose cytarabine and daunorubicin, complete remission was achieved in 65% of patients. In the primary efficacy population of patients evaluable for consolidation outcomes, consolidation with either 3x HD-AraC or MAC/MAMC/MAC did not result in any significant difference in 3-year overall (69% v 64%; P = .18) or disease-free survival (46% v 48%; P = .99) according to the intention-to-treat analysis. Furthermore, MAC/MAMAC/MAC led to additional GI and hepatic toxicity and a higher rate of infection and bleeding, resulting in significantly shorter 3-year overall survival in the per-protocol analysis compared with 3x HD-AraC (63% v 72%; P = .04). Conclusion: In younger adults with AML, multiagent consolidation using mitoxantrone and amsacrine in combination with high-dose cytarabine does not improve treatment outcome and confers additional toxicity.