Fludarabine-based cytoreductive regimen and T-cell-depleted grafts from alternative donors for the treatment of high-risk patients with Fanconi anaemia Journal Article

  

Authors:	Chaudhury, S.; Auerbach, A. D.; Kernan, N. A.; Small, T. N.; Prockop, S. E.; Scaradavou, A.; Heller, G.; Wolden, S.; O'Reilly, R. J.; Boulad, F.
Article Title:	Fludarabine-based cytoreductive regimen and T-cell-depleted grafts from alternative donors for the treatment of high-risk patients with Fanconi anaemia
Abstract:	Eighteen consecutive patients aged 5.5-24 years with Fanconi anaemia and diagnoses of aplastic anaemia (n = 8), myelodysplastic syndrome (n = 4), acute myeloid leukaemia (n = 6), received allogeneic haematopoietic stem cell transplants from alternative donors. All patients had been transfused, 13 had previously been treated with androgens and 14 had a history of infection. Donors were related human leucocyte antigen (HLA) mismatched for eight patients, unrelated HLA mismatched for seven patients and unrelated HLA matched for three patients. Cytoreduction included single dose total body irradiation (450 cGy), fludarabine (150 mg/m2) and cyclophosphamide (40 mg/kg). Immunosuppression included antithymocyte globulin and tacrolimus. Grafts were granulocyte colony-stimulating factor-mobilized, CD34+ T-cell-depleted peripheral blood stem cells in 15 patients and T-cell-depleted marrows in three. All 18 patients engrafted with 100% donor chimaerism; only one patient developed graft-versus-host disease (GVHD). With a median follow-up of 4.2 years, 13/18 patients were alive, 12 of these were disease-free. Five-year overall survival and disease-free survival were 72.2% and 66.6% respectively. Immune reconstitution was achieved at approximately 6 months post-transplant for most patients. These are encouraging results of T-cell-depleted transplants from alternative donors using fludarabine-based cytoreduction in 18 high-risk patients with Fanconi anaemia, with no evidence of rejection and minimal GVHD. © 2008 The Authors.
Keywords:	adolescent; adult; child; clinical article; preschool child; treatment outcome; child, preschool; survival analysis; acute granulocytic leukemia; overall survival; androgen; fludarabine; drug dose reduction; drug withdrawal; disease free survival; t-lymphocytes; cd34 antigen; cyclophosphamide; hematopoietic stem cell transplantation; transplantation; high risk patient; immunoregulation; drug hypersensitivity; chimera; hla matching; myelodysplastic syndrome; nonmyeloablative conditioning; whole body radiation; graft versus host reaction; transplantation conditioning; allogeneic hematopoietic stem cell transplantation; methylprednisolone; graft survival; t cell depletion; drug substitution; immunosuppressive treatment; tacrolimus; graft vs host disease; granulocyte colony stimulating factor; cd34 selection; lymphocyte depletion; alemtuzumab; vidarabine; thymocyte antibody; aplastic anemia; fanconi anemia; organ donor; histocompatibility testing; t-cell depletion; fanconi anaemia
Journal Title:	British Journal of Haematology
Volume:	140
Issue:	6
ISSN:	0007-1048
Publisher:	John Wiley & Sons
Date Published:	2008-03-01
Start Page:	644
End Page:	655
Language:	English
DOI:	10.1111/j.1365-2141.2007.06975.x
PUBMED:	18302713
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-39749121663&partnerID=40&md5=3bcc5cadf22d53a1dfa6da1824b44da9
Notes:	--- - "Cited By (since 1996): 15" - "Export Date: 17 November 2011" - "CODEN: BJHEA" - "Source: Scopus"

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