title: Risk-Adapted Approach to HLA-Matched Sibling Hematopoietic Cell Allografting: Impact of Adjusting Conditioning Intensity and Integrating Post-Transplant Therapeutic Interventions.
abstract: BACKGROUND
  Optimizing conditioning and post-transplant intervention may reduce non-relapse mortality and relapse, improving survival after allogeneic hematopoietic cell transplantation (allo-HCT).
  
  
  METHODS
  We used a risk-adapted intensity of busulfan at 130 mg/m(2)/day for either 2, 3, or 4 days, with a fixed dose of fludarabine (30 mg/m(2)/day for 5 days), and thymoglobulin (2.5 mg/kg/day for 2 days). Our algorithm was based on age, comorbiditie(s), and disease risk.
  
  
  RESULTS
  Fifty-three patients with hematological malignancies (median age, 37 years; range, 16-65 years), received an allograft from human leukocyte antigen identical siblings. Post-transplant therapy was initiated between days 30 and 60 after allo-HCT. Twenty-five of 26 patients who were planned for post allo-HCT therapy received it (10 with myeloid malignancies received 5-azacytidine, 5 with FLT-3 ITD acute myeloid leukemia received sorafenib, 4 with Philadelphia-positive acute lymphoblastic leukemia or chronic myelogenous leukemia in blast crisis received dasatinib, or dasatinib followed by imatinib, and 5 with acute lymphoblastic leukemia received intrathecal cytarabine). The remaining 27 patients (51%) did not receive post-transplant therapy because of lack of approval by third-party payers. After a median follow-up of 13 months (range, 2-57 months), 1-year non-relapse-mortality was 2%, and cumulative incidences of grade 2 to 4 acute graft-versus-host disease and all grades chronic graft-versus-host disease were 23% and 9%, respectively. The 2-year overall survival (95% vs. 61%; P = .04) and progression-free survival (81% vs. 53%; P = .05) were significantly better for patients in the post-transplant therapy group.
  
  
  CONCLUSIONS
  This risk-adapted combined approach of selecting conditioning intensity and integrating post-transplant therapies results in lower non-relapse-mortality and encouraging improvement in survival. Our findings warrant confirmation in a large prospective multicenter trial.
authors.affiliation: Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Jean
authors.initials: J
authors.lastname: El Cheikh
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Zaher K
authors.initials: ZK
authors.lastname: Otrock
authors.affiliation: Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Abd Assalam
authors.initials: AA
authors.lastname: Qannus
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.affiliation: Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon. Electronic address: bazarbac@aub.edu.lb.
authors.forename: Ali
authors.initials: A
authors.lastname: Bazarbachi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology / Q000517:prevention & control; D011182:Postoperative Care; D012189:Retrospective Studies; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens
keywords: 5-Azacytidine; Allogeneic stem cell transplantation; Dasatinib; Personalized conditioning; Sorafenib