Treatment of FLT3-ITD-positive acute myeloid leukemia relapsing after allogeneic stem cell transplantation with sorafenib.

Abstract

Patients with acute myeloid leukemia (AML) and internal tandem duplication of FMS-like tyrosine kinase receptor-3 gene (FLT3-ITD) mutation have poor prognoses and are often treated with allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. We treated 16 patients with FLT3-ITD-positive AML who relapsed after HSCT with sorafenib alone (n = 8) or in combination with cytotoxic chemotherapy (n = 8). The number of circulating blasts decreased in 80% of cases, but none of the patients achieved complete remission (CR); 3 achieved partial remission. Two patients were bridged to a second transplantation but both relapsed within 3 months of the transplantation. Median overall survival (OS) was 83 days, with none surviving more than a year. Sorafenib is not effective in the treatment of FLT3-ITD-positive AML relapsing after HSCT. Preventive strategies after HSCT may be more suitable for these high-risk patients.

• Authors: Manish Sharma, Farhad Ravandi, Ulas Darda Bayraktar, Alexandre Chiattone, Qaiser Bashir, Sergio Giralt, Julianne Chen, Muzaffar Qazilbash, Partow Kebriaei, Marina Konopleva, Michael Andreeff, Jorge Cortes, Deborah McCue, Hagop Kantarjian, Richard E Champlin, Marcos de Lima
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 17 Issue 12 Pg. 1874-7 (Dec 2011) ISSN: 1523-6536 [Electronic] United States
• PMID: 21767516 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzenesulfonates
• Phenylurea Compounds
• Protein Kinase Inhibitors
• Pyridines
• Niacinamide
• Sorafenib
• FLT3 protein, human
• fms-Like Tyrosine Kinase 3

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Benzenesulfonates (administration & dosage, therapeutic use)
• Combined Modality Therapy
• Female
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, enzymology, genetics, surgery)
• Male
• Middle Aged
• Niacinamide (analogs & derivatives)
• Phenylurea Compounds
• Prognosis
• Protein Kinase Inhibitors (therapeutic use)
• Pyridines (administration & dosage, therapeutic use)
• Recurrence
• Retrospective Studies
• Sorafenib
• Transplantation, Homologous (methods)
• Young Adult
• fms-Like Tyrosine Kinase 3 (antagonists & inhibitors, biosynthesis, genetics)