title: Treosulfan/fludarabine as an allogeneic hematopoietic stem cell transplant conditioning regimen for high-risk patients.
abstract: In recent years, new conditioning regimens have been explored in patients not eligible for conventional transplant with the aim to reduce transplant-related mortality. In a phase II multicentric prospective trial, we investigated the safety and feasibility of the treosulfan-fludarabine combination prior to allogeneic hematopoietic stem cell transplant in patients with various hematological malignancies not eligible for conventional regimens because of previous intensive treatment, older age, and comorbidities. Forty-six consecutive patients, median age 48 years (range 17-69), were enrolled. Sixteen of them were in complete remission, and 20 had a HSCT comorbidity index > or = 1. Forty-four patients had regular and sustained engraftment, and 39 out of 40 evaluable patients developed complete chimerism. Nonhematological toxicity was limited. Risk of transplant-related mortality was 9% (95% CI, 2-17%) at day +100 and plotted at 15% (95% CI, 7-22%) after 7 months. The estimated overall survival and progression-free survival with a median follow-up of 20 months were 51% and 38%, respectively. The estimated 30 months progression-free survival for patients transplanted in remission was 56%. The treosulfan-fludarabine combination is a reduced-toxicity but myeloablative regimen that can be proposed to patients not fitting criteria for conventional transplant regimens. Longer follow-up and further prospective studies are necessary to evaluate this regimen.
authors.affiliation: Unità Operativa Ematologia e Centro Trapianti Wilma Deplano Ospedale Oncologico Armando Businco, Cagliari.
authors.forename: Donatella
authors.initials: D
authors.lastname: Baronciani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Iori
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Bartolomeo
authors.forename: Federica
authors.initials: F
authors.lastname: Pilo
authors.forename: Martina
authors.initials: M
authors.lastname: Pettinau
authors.forename: Cristina
authors.initials: C
authors.lastname: Depau
authors.forename: Caterina
authors.initials: C
authors.lastname: Mico
authors.forename: Stella
authors.initials: S
authors.lastname: Santarone
authors.forename: Emanuele
authors.initials: E
authors.lastname: Angelucci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003131:Combined Modality Therapy; D015897:Comorbidity; D004066:Digestive System Diseases / Q000139:chemically induced; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012086:Reoperation; D012306:Risk; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D019653:Myeloablative Agonists; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine