Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome

How to manage acute promyelocytic leukemia

“…In 2009, the same working group 3 compared the results of APL93 trial and APL2000 trial and confirmed that high-dose Ara-C could significantly lower the cumulative incidence of relapse and ameliorate survival in highrisk patients, which was supported by both German AML Cooperative Group 74 and PETHEMA Group. 75 However, one should pay attention to the severe bone marrow suppression resulting from high-dose Ara-C, which could thereby increase the risk of serious infections.…”

Long‐term follow‐up of European APL 2000 trial, evaluating the role of cytarabine combined with ATRA and Daunorubicin in the treatment of nonelderly APL patients

“…Reducing the amount of CT in APL patients has been investigated in order to limit its toxicity. The PETHEMA and GIMEMA groups, in particular, reported very few relapses and deaths in CR with regimens combining ATRA and intercalating agents (idarubicin and mitoxantrone) without AraC, suggesting that AraC can be omitted from the treatment of APL, at least in standard-risk patients [i.e., with white blood cell (WBC) count <10,000/mm 3 ] [4,5].…”

“…Reducing the amount of CT in APL patients has been investigated in order to limit its toxicity. The PETHEMA and GIMEMA groups, in particular, reported very few relapses and deaths in CR with regimens combining ATRA and intercalating agents (idarubicin and mitoxantrone) without AraC, suggesting that AraC can be omitted from the treatment of APL, at least in standard-risk patients [i.e., with white blood cell (WBC) count <10,000/mm 3 ] [4,5].On the other hand, our APL 2000 trial randomizing AraC during induction and consolidation treatment, in patients aged 60 years with WBC count <10 G/l, was closed after the first interim analysis, made after a median follow-up of 24 months, due to significantly higher 2 year cumulative incidence of relapse (CIR) in the group without AraC [6,7].We present here long-term results of this trial, 7 years after the last patient inclusion, with a median follow-up of 103 months. …”

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

“…92 Among patients with intermediate risk, the relapse rate was reduced from 14% to 2.5% with the incorporation of ATRA; the 3-year DFS rate was 97% with ATRA consolidation versus 82% in historical controls. 92 Although the addition of ATRA to the high-risk group did improve relapse and DFS rates, there was room for improvement given a relapse rate of 21% and a 3-NCCN Guidelines Index AML 85 The recent AIDA-2000 trial of the Italian GIMEMA group has confirmed that inclusion of ATRA in consolidation significantly improved outcome, most notably for high-risk patients; the high-risk group received a consolidation regimen containing ATRA and cytarabine along with anthracyclines. 86 In this study, the 6-year cumulative incidence of relapse was 9% for patients in the high-risk group; the 6-year DFS and OS rates in this group were 84.5% and 83%, respectively.…”

“…83,85 To improve patient outcome, the PETHEMA LPA99 trial and the GIMEMA AIDA-0493 study were modified to incorporate the combination of ATRA with cytarabine either during induction (LPA2005) 85 or during consolidation (AIDA-2000). 86 The improved outcomes in both these studies suggest a supra-additive effect with ATRA plus cytarabine, independent of the anthracycline.…”