Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemia

Br J Haematol. 2005 Jul;130(1):99-106. doi: 10.1111/j.1365-2141.2005.05549.x.

Abstract

Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen-matched related donors. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2-3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0.001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44-58) months and 16 (3-52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage*
  • Drug Administration Schedule
  • Fanconi Anemia / drug therapy
  • Fanconi Anemia / immunology
  • Fanconi Anemia / surgery*
  • Female
  • Graft vs Host Disease
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Statistics, Nonparametric
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide