Acute myeloid leukemia after myelodysplastic syndrome and failure of therapy with hypomethylating agents: an emerging entity with a poor prognosis.

Abstract

We assessed the outcomes of 63 patients with acute myeloid leukemia (AML) arising from myelodysplastic syndrome (MDS) after hypomethylating agent failure. Their median age was 63 years. All 63 patients had received ≥ 1 salvage regimens for AML, and 35 patients (55%) had received ≥ 2. Of the 31 patients (49%) who had received high-dose cytarabine (HDAC) at first relapse, 2 (6%) achieved complete remission (CR) and 4 (13%) CR with incomplete platelet recovery (overall response rate, 19%). Of the 32 patients (51%) who had received other treatments, including investigational agents, 4 (12%) achieved CR and 4 (12%) CR with incomplete platelet recovery (overall response rate, 24%). The median response duration was 20 weeks. With a median follow-up of 42 months from the AML diagnosis, the median survival (21 weeks) was similar between the 2 groups. The 1- and 2-year survival rate was 19% and 8%, respectively. Multivariate analysis identified low albumin, HDAC treatment, and platelet count < 50 × 10(9)/L as independent adverse factors for CR and a platelet count < 50 × 10(9)/L and age > 65 years as independent adverse factors for survival. Thus, the outcome of AML evolving from MDS after hypomethylating agent failure is poor and not improved with HDAC. Novel therapies directed toward this emerging entity are urgently needed.

• Authors: Elias Jabbour, Hady Ghanem, Xuelin Huang, Farhad Ravandi, Guillermo Garcia-Manero, Susan O'Brien, Stephan Faderl, Sherry Pierce, Sangbum Choi, Srdan Verstovsek, Mark Brandt, Jorge Cortes, Hagop Kantarjian
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 14 Issue 2 Pg. 93-7 (Apr 2014) ISSN: 2152-2669 [Electronic] United States
• PMID: 24447728 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Cytarabine

Topics

• Acute Disease
• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cytarabine (administration & dosage)
• DNA Methylation (drug effects)
• Female
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Leukemia, Myeloid (pathology, therapy)
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Myelodysplastic Syndromes (drug therapy, genetics)
• Outcome Assessment, Health Care (statistics & numerical data)
• Prognosis
• Proportional Hazards Models
• Remission Induction
• Salvage Therapy (methods)
• Survival Analysis
• Transplantation, Homologous