Successful engraftment without radiation after fludarabine-based regimen in Fanconi anemia patients undergoing genotypically identical donor hematopoietic cell transplantation

Pediatr Blood Cancer. 2006 May 1;46(5):630-6. doi: 10.1002/pbc.20538.


Background: To potentially reduce late effects of malignancy, chronic graft-versus-host disease (GVHD), endocrinopathy, and infertility in patients with Fanconi anemia (FA) undergoing HLA-matched related donor hematopoietic cell transplantation (HCT), we developed a regimen using fludarabine (FLU), cyclophosphamide (CY), and anti-thymocyte globulin (ATG) followed by infusion of T-cell depleted (TCD) bone marrow (BM) or unmanipulated umbilical cord blood (UCB). GVHD prophylaxis consisted of cyclosporine and short course methylprednisolone.

Procedure: Between April 2000 and June 2003, 11 patients (10 aplastic anemia (AA), 1 myelodysplastic syndrome (MDS)) underwent HCT using this regimen. Stem cell sources were BM and UCB in eight and three patients, respectively.

Results: All patients demonstrated primary engraftment. Median days to neutrophil and platelet engraftment were 11 days (range 9-21) and 38 days (range 19-381), respectively. No patient developed GVHD after primary HCT. The patient with MDS relapsed with AML and a maternal donor recipient experienced secondary graft failure. For the nine FA patients with AA who underwent HLA-identical sibling donor HCT, the Kaplan-Meier estimates of overall survival and event-free survival (EFS) at 2 years are 100% and 82%, respectively, at a median follow-up of 2.9 years (range 1.9-4.8).

Conclusions: In summary, a FLU-based, non-irradiation approach is effective for FA patients with AA undergoing HLA-identical sibling donor HCT.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antilymphocyte Serum / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Child
  • Child, Preschool
  • Chronic Disease
  • Cyclophosphamide / administration & dosage
  • Cyclosporine / therapeutic use
  • Fanconi Anemia / immunology
  • Fanconi Anemia / therapy*
  • Female
  • Fetal Blood / cytology
  • Fetal Blood / immunology
  • Graft Survival / drug effects*
  • Graft vs Host Disease
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Methylprednisolone / therapeutic use
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / therapy
  • Neoplasm Recurrence, Local
  • Survival Rate
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives


  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Cyclosporine
  • Cyclophosphamide
  • Vidarabine
  • fludarabine
  • Methylprednisolone