Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy

H. Joachim Deeg, Margaret O'Donnell, Jakub Tolar, Rajni Agarwal, Richard E. Harris, Stephen A. Feig, Mary C. Territo, Robert H. Collins, Peter A. McSweeney, Edward A. Copelan, Shakila P. Khan, Ann Woolfrey, Barry Storer

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

In 87 patients with aplastic anemia who failed to respond to immunosuppressive treatment, we determined the minimal dose of total body irradiation (TBI) required when added to antithymocyte globulin (ATG, 30 mg/kg x 3) plus cyclophosphamide (CY, 50 mg/kg x 4) to achieve engraftment of unrelated donor marrow. TBI was started at 3 x 200 cGy, to be escalated or deescalated in steps of 200 cGy depending on graft failure or toxicity. Patients were aged 1.3 to 53.5 years (median, 18.6 years). The interval from diagnosis to transplantation was 3 to 328 months (median, 14.6 months). Donors were HLA-A, -B, -C, -DR, and -DQ identical for 62 patients, and nonidentical for 1 to 3 HLA loci at the antigen or allele level for 25. The dose-limiting toxicity was diffuse pulmonary injury. The optimum TBI dose was 1 x 200 cGy. Nine patients did not tolerate ATG and were prepared with CY + TBI. Graft failure occurred in 5% of patients. With a median follow-up of 7 years, 38 (61%) of 62 HLA-identical, and 10 (40%) of 25 HLA-nonidentical transplant recipients are surviving. The highest survival rate with HLA-identical transplants was observed at 200 cGy TBI. Thus, low-dose TBI + CY + ATG conditioning resulted in excellent outcome of unrelated transplants in patients with aplastic anemia who had received multiple transfusions.

Original languageEnglish (US)
Pages (from-to)1485-1491
Number of pages7
JournalBlood
Volume108
Issue number5
DOIs
StatePublished - Sep 1 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Deeg, H. J., O'Donnell, M., Tolar, J., Agarwal, R., Harris, R. E., Feig, S. A., Territo, M. C., Collins, R. H., McSweeney, P. A., Copelan, E. A., Khan, S. P., Woolfrey, A., & Storer, B. (2006). Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy. Blood, 108(5), 1485-1491. https://doi.org/10.1182/blood-2006-03-005041