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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1485-1491.
Prepublished online as a Blood First Edition Paper on May 9, 2006; DOI 10.1182/blood-2006-03-005041.
 Previous Article | Next Article 
Submitted March 8, 2006
Accepted April 11, 2006
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 Feig, Mary C. Territo, Robert H. Collins, Peter A. McSweeney, Edward A. Copelan, Shakila P. Khan, Ann Woolfrey, and Barry Storer
Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine
City of Hope National Medical Center
University of Minnesota
Stanford University
Cincinnati Children's Hospital Medical Center
UCLA
University of Texas, Southwestern Medical Center
University of Colorado
Ohio State University
Mayo Clinic
Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA
* Corresponding author; email: jdeeg{at}fhcrc.org.
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 3x 200 cGy, to be escalated/de-escalated in steps of 200 cGy dependent upon graft failure/toxicity. Patients were 1.3-53.5 (median 18.6) years old. The interval from diagnosis to transplant was 3-328 (median 14.6) months. Donors were HLA-A, -B, - C, - DR, and -DQ identical for 62 patients, and nonidentical for one to three HLA loci at the antigen or allele level for 25. The dose-limiting toxicity was diffuse pulmonary injury. The optimum TBI dose was 1x200 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 multiply transfused patients with aplastic anemia.
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