title: Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia.
abstract: BACKGROUND
  Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results.
  
  
  METHODS
  The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia.
  
  
  RESULTS
  The median age of the patients was 46 years (range, 15-57 years). Sorafenib was introduced at a median of 70 days (range, 29-337 days) after HSCT. The median treatment duration was 8.4 months (range, 0.2-46 months). Eleven patients experienced treatment toxicities, mainly of grade 1 to 2 (graded according to the National Cancer Institute Common Toxicity Criteria [version 4.0]). Dose reduction or withdrawal was required in 4 patients and 4 patients, respectively. The persistence of toxicity prompted treatment withdrawal in 1 patient. Clinical improvement followed dose modifications. Thirteen patients experienced chronic graft-versus-host disease (limited in 9 patients and extensive in 4 patients), resulting in dose reduction in 5 patients followed by withdrawal in 1 of these individuals. At a median follow-up of 18 months (range, 4-48 months), 25 patients were alive (all of whom were in complete molecular remission) and 18 were still receiving treatment, with 1-year overall survival and progression-free survival rates of 92% ± 6% and 92% ± 5%, respectively.
  
  
  CONCLUSIONS
  Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT. Cancer 2017;123:2867-74. © 2017 American Cancer Society.
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.|Department of Hematology and Marrow Transplantation, Federico II University, Naples, Italy.
authors.forename: Giorgia
authors.identifier: http://orcid.org/0000-0002-5201-1786
authors.initials: G
authors.lastname: Battipaglia
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ruggeri
authors.affiliation: Bone Marrow Transplantation Program, Department of Internal Medicine, American Universit6y of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Radwan
authors.identifier: http://orcid.org/0000-0001-9275-3840
authors.initials: R
authors.lastname: Massoud
authors.affiliation: Bone Marrow Transplantation Program, Department of Internal Medicine, American Universit6y of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Jean
authors.initials: J
authors.lastname: El Cheikh
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Jestin
authors.affiliation: Bone Marrow Transplantation Program, Department of Internal Medicine, American Universit6y of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Antar
authors.affiliation: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Syed Osman
authors.initials: SO
authors.lastname: Ahmed
authors.affiliation: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Walid
authors.initials: W
authors.lastname: Rasheed
authors.affiliation: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Marwan
authors.initials: M
authors.lastname: Shaheen
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Ramdane
authors.initials: R
authors.lastname: Belhocine
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Eolia
authors.initials: E
authors.lastname: Brissot
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Remy
authors.initials: R
authors.lastname: Dulery
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Eder
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Federica
authors.initials: F
authors.lastname: Giannotti
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Isnard
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Simona
authors.initials: S
authors.lastname: Lapusan
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Rubio
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vekhoff
authors.affiliation: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.
authors.forename: Ollivier
authors.initials: O
authors.lastname: Legrand
authors.affiliation: Hematology and Cellular Therapy Service, Saint Antoine Hospital, AP-HP, Paris, France.|Hospital Saint-Antoine, Paris University UPMC, Paris, France.|INSERM, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Bone Marrow Transplantation Program, Department of Internal Medicine, American Universit6y of Beirut Medical Center, Beirut, Lebanon.|Department of Cell Biology, Anatomy and Physiological Sciences, American University of Beirut, Beirut, Lebanon.
authors.forename: Ali
authors.initials: A
authors.lastname: Bazarbachi
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077157:Sorafenib; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D051941:fms-Like Tyrosine Kinase 3
keywords: Fms-like tyrosine kinase 3 (FLT3); acute myeloid leukemia (AML); allogeneic stem cell transplantation; maintenance; sorafenib