title: Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia.
abstract: Sixty-two adults underwent marrow or blood stem cell transplantation from an HLA-matched related donor using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen for treatment of advanced myelodysplastic syndrome (MDS) (refractory anemia with excess blasts with or without transformation) or acute myelogenous leukemia (AML) past first remission. All evaluable patients engrafted and had complete donor chimerism. A grade 3-4 regimen-related toxicity occurred in eight (13%) patients, and a diagnosis of MDS was the only independent risk factor for grade 3-4 regimen-related toxicity (hazard ratio 9.25, P = 0.01). Day-100 treatment-related mortality (TRM) was 19%. Poor-prognosis cytogenetics increased the risk of day-100 TRM (hazard ratio 11.4, P = 0.003), and use of tacrolimus for graft-versus-host disease prophylaxis reduced the risk of day-100 TRM (hazard ratio 0.13, P = 0.027). For all patients, the three-year relapse rate was 43% (95% CI, 28%-58%). Refractoriness to conventional induction chemotherapy prior to transplantation was an independent risk factor for relapse (hazard ratio 10.8, P = 0.02). Three-year survival was 26% (95% CI, 14%-37%); survival rates were 29% for those transplanted for AML in second remission, 31% transplanted for AML in relapse, and 17% with MDS, and there were no independent risk factors for survival. TBC is an active preparative regimen for advanced AML. Patients with advanced MDS appeared to have a higher risk of toxicity and early mortality, and alternative preparative regimens should be considered for these patients.
authors.affiliation: Department of Blood and Marrow Transplantation, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bibawi
authors.forename: D
authors.initials: D
authors.lastname: Abi-Said
authors.forename: L
authors.initials: L
authors.lastname: Fayad
authors.forename: P
authors.initials: P
authors.lastname: Anderlini
authors.forename: N T
authors.initials: NT
authors.lastname: Ueno
authors.forename: R
authors.initials: R
authors.lastname: Mehra
authors.forename: I
authors.initials: I
authors.lastname: Khouri
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: J
authors.initials: J
authors.lastname: Gajewski
authors.forename: M
authors.initials: M
authors.lastname: Donato
authors.forename: D
authors.initials: D
authors.lastname: Claxton
authors.forename: I
authors.initials: I
authors.lastname: Braunschweig
authors.forename: K
authors.initials: K
authors.lastname: van Besien
authors.forename: M
authors.initials: M
authors.lastname: Andreeff
authors.forename: B S
authors.initials: BS
authors.lastname: Andersson
authors.forename: E H
authors.initials: EH
authors.lastname: Estey
authors.forename: R
authors.initials: R
authors.lastname: Champlin
authors.forename: D
authors.initials: D
authors.lastname: Przepiorka
mesh_terms: D000293:Adolescent; D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000628:therapy; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000633:toxicity; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000401:mortality / Q000592:standards; D002066:Busulfan / Q000008:administration & dosage / Q000633:toxicity; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality / Q000592:standards; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000401:mortality / Q000628:therapy*; D013852:Thiotepa / Q000008:administration & dosage / Q000633:toxicity; D019172:Transplantation Conditioning / Q000592:standards; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000592:standards*; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan