Comparison of Conditioning Regimens with or without Total Body Irradiation in Bone Marrow Transplantation from an Alternative Donor.

Abstract

An optimum conditioning regimen is indispensable in improving outcomes for patients with acquired aplastic anemia (AA) who receive bone marrow transplantation (BMT) from an alternative donor. Although high-dose total body irradiation (TBI) is effective in enhancing engraftment, intensive conditioning regimens are associated with increased regimen-related toxicity, which results in a decreased success rate. Currently, two different approaches are primarily used; a conditioning regimen including low-dose TBI and a fludarabin-based regimen without TBI. We attempt to clarify the efficacy and regimen-related toxicity of these two approaches. Ten patients (7 males, 3 females; median age 12y; range 9–17y) underwent an alternative donor transplant following a conditioning regimen with low-dose TBI (TBI group); patients received cyclophosphamide (50 mg/kg/d on days −5 to −2), antithymocyte globulin (Thymoglobulin, 2.5 mg/kg/d on days −5 to −2) and TBI (2.5 Gy x 2 on day −1). The donor was unrelated in 9 patients (3 were serologically HLA A or B antigen mismatched; 3 were serologically HLA DR antigen mismatched, 1 was both serologically and genotypically DR antigen mismatched; 1 was genotypically DRB1 mismatched; 1 was a genotypically complete match) and was a family member in 1 patient (serologically HLA A-mismatched father). Twelve patients (6 males, 6 females; median age, 11 y; range 2–20 y) received a conditioning regimen of fludarabine (25 mg/kg/d on days −5 to −2), cyclophosphamide (750 mg/m 2 /d on days −5 to −2), thymoglobulin (1.5 mg/kg/d on days −5 to −2) and thoracoabdominal irradiation (TAI, 3Gy x 1 on day −1) (TAI group). The donor was unrelated in 11 patients (8 were genotypically complete matches, and 3 were genotypically DRB1 antigen mismatched) and a family member in 1 patient (3 antigen-mismatched mother). The source of stem cells was unmanipulated bone marrow. Graft versus host disease (GVHD) prophylaxis consisted of tacrolimus (0.02 mg/kg from day −1) and short-term methotrexate. Rejection was seen in one patient in each group. The doses of infused nucleated marrow cells were less than 2.0 x 10 8 /kg in both patients, and both patients then received a second transplant and achieved full donor chimerism. Acute GVHD grade II-IV developed in 2/10 evaluable patients in the TBI group and in 3/12 patients in the TAI group. Chronic GVHD developed in 5/9 evaluable patients in TBI group and 3/10 evaluable patients in TAI group. Median follow up was 9 months (4–27 months) in the TBI group and 21 months (3–33 months) in the TAI group. Both conditioning regimens were well tolerated and effective even in HLA-mismatched unrelated donor transplantation. Long-term follow up is warranted in order to compare the late sequelae in both regimens.