title: 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.affiliation: Department of Stem Cell Transplantation, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Sharma
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Ulas Darda
authors.initials: UD
authors.lastname: Bayraktar
authors.forename: Alexandre
authors.initials: A
authors.lastname: Chiattone
authors.forename: Qaiser
authors.initials: Q
authors.lastname: Bashir
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Julianne
authors.initials: J
authors.lastname: Chen
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Qazilbash
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Deborah
authors.initials: D
authors.lastname: McCue
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D000077157:Sorafenib; D014184:Transplantation, Homologous / Q000379:methods*; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3