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

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.

• Authors: J Zanis-Neto, M E D Flowers, C R Medeiros, M A Bitencourt, C M Bonfim, D C Setúbal, V Funke, J Sanders, H J Deeg, H P Kiem, P Martin, W Leisenring, R Storb, R Pasquini
• Journal: British journal of haematology (Br J Haematol) Vol. 130 Issue 1 Pg. 99-106 (Jul 2005) ISSN: 0007-1048 [Print] England
• PMID: 15982351 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Immunosuppressive Agents
• Cyclophosphamide

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Cyclophosphamide (administration & dosage)
• Drug Administration Schedule
• Fanconi Anemia (drug therapy, immunology, 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