title: Prospective phase II trial to evaluate the complications and kinetics of chimerism induction following allogeneic hematopoietic stem cell transplantation with fludarabine and busulfan.
abstract: This prospective trial assessed the safety and efficacy of allogeneic hematopoietic stem cell transplantation from a HLA-matched donor with a reduced-intensity regimen (RIST) consisting of iv fludarabine 30 mg/m(2) for 6 days and oral busulfan 4 mg/kg/day for 2 days in patients older than 50 years with hematological malignancies. Cyclosporine alone or cyclosporine with short-term methotrexate was randomized for graft-versus-host disease prophylaxis. After 30 patients had been enrolled, an interim analysis was performed, and this report focuses on a precise evaluation of the toxicity profile and chimerism kinetics. Sustained engraftment in all patients, no severe regimen-related toxicity (RRT) within 20 days, and no transplant-related mortality through Day 100 were observed. T-cell (CD3+) full-donor (over 90%) chimerism was observed in 22 of the 30 patients, while the remaining eight had mixed-donor chimerism over 77% on Day 90. Thereafter, five subsequently converted to full-donor chimerism without donor lymphocyte infusion by day 120 (n = 4) or Day 180 (n = 1). Two showed persistent mixed chimerism without relapse through Day 180. Grade III-IV acute graft-versus-host disease and extensive chronic graft-versus-host disease occurred in 10% and 73%, respectively. With a median follow-up of 1.5 years, overall survival and disease-free survival at 1 year was 83% and 62%, respectively. Seven patients hematologically relapsed overall, and five of them had myelodysplastic syndrome with poor prognostic factors. In older patients, RIST with fludarabine and busulfan was associated with acceptable toxicities and a satisfactory antileukemia effect, regardless of the early chimerism status.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. akiko_saito@dfci.harvard.edu
authors.forename: Akiko M
authors.initials: AM
authors.lastname: Saito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kami
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Mori
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
authors.forename: Ritsuro
authors.initials: R
authors.lastname: Suzuki
authors.forename: Shin
authors.initials: S
authors.lastname: Mineishi
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takami
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hara
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Akiko
authors.initials: A
authors.lastname: Hori
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takaue
mesh_terms: D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000097:blood / Q000401:mortality / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000401:mortality / Q000601:surgery; D011183:Postoperative Complications / Q000401:mortality; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000401:mortality / Q000706:statistics & numerical data; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008727:Methotrexate