Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups

Marysia Hengeveld,Maria C Petti,Franco Mandelli,Stefan Suciu,Pietro Leoni,Sergio Amadori,Guiseppe Fioritoni,Enrica Morra,Bruno Rotoli,Petra Muus,Luigi Resegotti,Robert Zittoun,Giorgina Specchia,Marco Vignetti,Theo De Witte,Joseph Thaler,Paola Fazi,Matthias Karrasch,Jean-Pierre Marie

doi:10.1007/s00277-012-1436-z

Abstract

SummaryThe most effective post-remission treatment to maintain complete remission (CR) in adults aged between 46 and 60 years with acute myeloid leukaemia (AML) is uncertain. Previously untreated patients with AML in CR after induction chemotherapy with daunorubicin and cytarabine were randomized between two intensive courses of consolidation therapy containing high-dose cytarabine, combined with amsacrine or daunorubicin and a standard consolidation and maintenance therapy containing standard dose cytarabine and daunorubicin. One hundred fifty-eight CR patients were assigned to the intensive group and 157 patients to the standard group. After a median follow-up of 7.5 years, the 4-year survival rate was 32 % in the intensive group versus 34 % in the standard group (P = 0.29). In the intensive group, the 4-year relapse incidence was lower than in the standard group: 55 and 75 %, respectively (P = 0.0003), whereas treatment-related mortality incidence was higher: 22 versus 3 % (P < 0.0001). Two intensive consolidation courses containing high-dose cytarabine as post-remission treatment in patients with AML aged between 46 and 60 years old did not translate in better long-term outcome despite a 20 % lower relapse incidence. Better supportive care and prevention of treatment-related complications may improve the overall survival after intensified post-remission therapy in this age group.

Highlights

Younger than age 60 years, with acute myeloid leukaemia (AML) may achieve complete remission (CR) in 60 to 80 % of the cases treated with intensive remission induction courses usually consisting cytarabine (Ara-C) combined with an anthracycline/anthracycline-like drug [1,2,3,4,5]
Patients with chronic myeloid leukaemia or other myeloproliferative diseases in blast crisis were excluded, as were patients who had leukaemia supervening after other myeloproliferative diseases or patients who had a preceding myelodysplastic syndrome for more than 6 months
Between November 1986 and April 1993, 659 patients have been registered in the study by 44 institutions

Summary

Introduction

Younger than age 60 years, with acute myeloid leukaemia (AML) may achieve complete remission (CR) in 60 to 80 % of the cases treated with intensive remission induction courses usually consisting cytarabine (Ara-C) combined with an anthracycline/anthracycline-like drug [1,2,3,4,5]. Most patients receive post-remission therapy, which may consist of consolidation/maintenance chemotherapy, autologous or allogeneic stem cell transplantation [2,3,4]. Both allogeneic and autologous stem cell transplantation is associated with higher treatment-related morbidity and mortality patients with the age between 46 and 60 years compared to younger patients [6]. These patients are usually treated with consolidation and/or maintenance chemotherapy only [2, 4]. Despite many studies on post-remission therapy to prevent relapse with chemotherapy with maximal efficiency and minimal toxicity, an effective schedule for this age group has not been established until now [2, 4, 7,8,9,10,11,12,13,14,15]

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