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


METHODS
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.
Tan
Poh-Lin
PL
Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Wagner
John E
JE
Auerbach
Arleen D
AD
Defor
Todd E
TE
Slungaard
Arne
A
Macmillan
Margaret L
ML
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000627:therapeutic use; D005199:Fanconi Anemia / Q000276:immunology / Q000628:therapy*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects*; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000628:therapy; D009364:Neoplasm Recurrence, Local; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D008775:Methylprednisolone