Marrow transplantation from unrelated donors iudt in patients with aplastic anemia (AA) who have failed immunosuppressive therapy

Under the auspices of the NMDP we developed a network and database for collaborative prospective studies of UDT in patients (pts.) with AA. At 7 centers, 20 pts. with AA who did not have a related donor and had failed immunosuppresstve therapy were entered. Pts. were 5-46 (median 29) years old. Disease duration was 4-96 (median 12.2) months. In 17 pts. the donor was HLA-matched, in 3, one HLA antigen mismatched. All pts. were scheduled to receive cyclophosphamide (CY) 4 x 50 mg/kg/day and anttthymocyte globulin (ATG) 30 mg/kg/day for 3 doses followed by total body irradiation (TBII starting at 3 x 200 cGy (2 fractions/day) to be (de-)escalated depending upon efficacy (engraftment) or toxicity. Methotrexate and cyclosporine were given for GVHD prophylaxis. Three pts. reacted to ATG and received CY, 2 x 60 mg/kg and TBI 6 x 200 cGy; all 3 engrafted and survive at 13, 16 and 25 months, respectively. Seventeen pts. received CY, ATG and 3 {or 2) x 200 cGy TBI. All 3 HLAnonidentical recipients (given 3 x 200 cGy] died from regimen- related toxicity or infection. All 14 HLA-identical recipients achieved engraftment. Four died with regimen-related toxicity (3/7 given 3 x 200 cGy; 117 given 2 x 200 cGy), 2 with fungal infection and one with chronic GVHD. Seven pts. survive at 1 -24 (median 15) months. In conclusion, these results with UDT in patients with AA who have failed immunosuppressive therapy are encouraging; currently 59% of HLA-matched recipients are surviving. Further reduction of the intensity of conditioning may allow to further reduce toxicity.