Treatment of FLT3-ITD-positive Acute Myeloid Leukemia Relapsing After Allogeneic Stem Cell Transplantation With Sorafenib

Biol Blood Marrow Transplant. 2011 Dec;17(12):1874-7. doi: 10.1016/j.bbmt.2011.07.011. Epub 2011 Jul 20.

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.

MeSH terms

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

Substances

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