title: Allogeneic Hematopoietic Stem Cell Transplantation in FLT3-ITD-Positive Acute Myelogenous Leukemia: The Role for FLT3 Tyrosine Kinase Inhibitors Post-Transplantation.
abstract: In recent years, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become increasingly common in patients with acute myelogenous leukemia (AML) due to improved donor availability and the use of nonmyeloablative regimens. However, despite the potential clinical gains with allo-HSCT, the post-transplantation outcomes for many patients, especially those with high-risk disease, remain dismal. Patients with AML who have internal tandem duplication mutations in the tyrosine kinase receptor FLT3 (FLT3-ITD) face particularly poor outcomes, even after allo-HSCT, which appears to only partially mitigate the poor prognosis associated with this mutation. Experimental treatments to reduce the likelihood of relapse and improve survival following allo-HSCT include maintenance with FLT3-specific tyrosine kinase inhibitors (TKIs), several of which are currently being evaluated in clinical studies. Preliminary data and case reports suggest that FLT3 TKIs can be effective in the post-transplantation setting, particularly for patients with FLT3-ITD mutations. Improvements in donor matching, transplantation procedures, and supportive care have allowed a greater number of patients to undergo allo-HSCT than ever before. For these patients, it is essential to identify effective post-transplantation therapies to reduce the risk of relapse and improve disease-free survival.
authors.affiliation: Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address: gschiller@mednet.ucla.edu.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schiller
authors.affiliation: Articulate Science, LLC, Atlanta, Georgia.
authors.forename: Pamela
authors.initials: P
authors.lastname: Tuttle
authors.affiliation: Weill Cornell Medical College, Division of Hematology/Oncology, New York, New York.
authors.forename: Pinkal
authors.initials: P
authors.lastname: Desai
mesh_terms: D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020080:Tandem Repeat Sequences; D014184:Transplantation, Homologous; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D047428:Protein Kinase Inhibitors; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myelogenous leukemia; Allogeneic hematopoietic stem cell transplantation; FLT3; FLT3-ITD; Tyrosine kinase inhibitor