title: Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders.
abstract: Allogeneic hematopoietic cell transplantation (HCT) is the only curative strategy for patients with myelodysplastic syndrome (MDS) and myeloproliferative disorders (MPD). We report the results of 148 patients (median age = 59 years old) with de novo MDS (n = 40), acute myelogenous leukemia (AML) after antecedent MDS/MPD (n = 49), treatment-related MDS (t-MDS) (n = 25), MPD (n = 27), and chronic myelomonocytic leukemia (CMML) (n = 7) who underwent allogeneic HCT using a conditioning regimen of low-dose total body irradiation (TBI) alone (200 cGy) on day 0 (n = 5) or with the addition of fludarabine (Flu) 30 mg/m(2)/day on days -4 to -2 (n = 143). Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil (MMF). Seventy-five patients (51%) received an allograft from a matched related donor (MRD), and 73 patients (49%) were recipients of unrelated donor (URD) grafts. There was no significant difference in the incidence of acute (gr II-IV) and chronic extensive graft-versus-host disease (aGVHD, cGVHD) between the recipients of related and unrelated donor grafts. By day +28, 75% of patients demonstrated mixed T cell chimerism. Graft rejection was seen in 15% of patients. With a median follow-up of 47 (range: 6-89) months, the 3-year relapse-free survival (RFS) and overall survival (OS) are both 27% for all patients, with a relapse incidence of 41%. The 3-year RFS for the patients with de novo MDS, AML after antecedent MDS/MPD, t-MDS, MPD, and CMML were 22%, 20%, 29%, 37%, and 43%, respectively, and the 3-year OS was 20%, 23%, 27%, 43%, and 43%, respectively. The 3-year nonrelapse mortality (NRM) was 32%. Factors associated with a lower risk of relapse were the development of extensive cGVHD and having a low risk or intermediate-1 risk International Prognostic Score for the de novo MDS patients. Nonmyeloablative HCT confers remissions in patients who otherwise were not eligible for conventional HCT but for whom relapse is the leading cause of treatment failure.
authors.affiliation: Stanford University Medical Center, Stanford, California 94305-5623, USA. glaport@stanford.edu
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Bart L
authors.initials: BL
authors.lastname: Scott
authors.forename: Monic J
authors.initials: MJ
authors.lastname: Stuart
authors.forename: Thoralf
authors.initials: T
authors.lastname: Lange
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Edward D
authors.initials: ED
authors.lastname: Agura
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: Ruby M
authors.initials: RM
authors.lastname: Wong
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Finn B
authors.initials: FB
authors.lastname: Petersen
authors.forename: James C
authors.initials: JC
authors.lastname: Wade
authors.forename: Elliot
authors.initials: E
authors.lastname: Epner
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Bethge
authors.forename: Peter T
authors.initials: PT
authors.lastname: Curtin
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Karl G
authors.initials: KG
authors.lastname: Blume
authors.forename: Rainer F
authors.initials: RF
authors.lastname: Storb
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D015477:Leukemia, Myelomonocytic, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D009196:Myeloproliferative Disorders / Q000628:therapy*; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
chemical_list: D014740:Vidarabine; C024352:fludarabine