title: Stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts.
abstract: We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA), using T cell-depleted two HLA-allele disparate related peripheral blood stem cell transplants (PBSCTs). Patient 1, a 5-year-old male with FA and aplastic anaemia, initially received an HLA two-antigen mismatched unrelated cord blood transplant and failed to engraft. He received fludarabine (Flu) and cyclophosphamide (Cy), followed by a CD34(+) E-rosette(-) (CD34(+)E(-)), T cell-depleted, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCT from his HLA B-DRB1 mismatched father. He received anti-thymocyte globulin (ATG), steroids, FK506 and G-CSF after transplant for rejection and graft-versus-host disease (GVHD) prophylaxis. The patient is now 23 months after SCT with no evidence of GVHD and with full haematopoietic and immune reconstitution. Patient 2, a 10-year-old boy with FA and myelodysplastic syndrome, received single-dose total body irradiation (SDTBI), Flu and Cy followed by a CD34(+)E(-), T-cell-depleted, G-CSF-mobilized PBSCT from his HLA B-DRB1 mismatched sister. He also received ATG, steroids, FK506 and G-CSF after transplant. The patient is now 12 months after SCT in complete remission with no evidence of GVHD. Absolute neutrophil counts (ANC) of > 1 x 10(9)/l were achieved on day 11 and day 10 post transplant respectively. Both patients are fully engrafted. In summary, we report two successful T-cell-depleted stem cell transplants from mismatched related donors for the treatment of Fanconi anaemia, using a fludarabine-based cytoreduction. Both patients experienced minimal toxicity, rapid engraftment and no GVHD.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. bouladf@mskcc.org
authors.forename: F
authors.initials: F
authors.lastname: Boulad
authors.forename: A
authors.initials: A
authors.lastname: Gillio
authors.forename: T N
authors.initials: TN
authors.lastname: Small
authors.forename: D
authors.initials: D
authors.lastname: George
authors.forename: V
authors.initials: V
authors.lastname: Prasad
authors.forename: J
authors.initials: J
authors.lastname: Torok-Castanza
authors.forename: A D
authors.initials: AD
authors.lastname: Regan
authors.forename: N
authors.initials: N
authors.lastname: Collins
authors.forename: A D
authors.initials: AD
authors.lastname: Auerbach
authors.forename: N A
authors.initials: NA
authors.lastname: Kernan
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Reilly
mesh_terms: D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D005199:Fanconi Anemia / Q000276:immunology / Q000628:therapy*; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D016559:Tacrolimus / Q000008:administration & dosage; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D016559:Tacrolimus