Unmanipulated HLA 2-3 antigen–mismatched (haploidentical) bone marrow transplantation using only pharmacological GVHD prophylaxis

Objective The incidence of severe graft-vs-host disease (GVHD) in unmanipulated human leukocyte antigen (HLA) 2-3 antigen–mismatched bone marrow transplantation (BMT) using cyclosporine and methotrexate as GVHD prophylaxis is 80% to 90%. We investigated whether pharmacological GVHD prophylaxis consisting of four drugs, including a steroid, effectively suppressed GVHD in this transplantation setting. Materials and Methods Thirty patients who had hematologic malignancies at an advanced stage or with poor prognosis underwent allogeneic BMT using a myeloablative preconditioning regimen consisting of cyclophosphamide (60 mg/kg × 2), total body irradiation (8–10 Gy), and fludarabine (30 mg/m 2 × 4) with or without cytosine arabinoside (2 g/m 2 × 4), and GVHD prophylaxis consisting of a combination of tacrolimus, methotrexate, mycophenolate mofetil, and methylprednisone (2 mg/kg). Early therapeutic intervention for GVH reaction or grade I GVHD was performed, and steroid was slowly tapered. Results All patients achieved donor-type engraftment. Neutrophil (>0.5 × 10 9 /L) and platelet (>20 × 10 9 /L) engraftment was achieved on day 13 and on day 30, respectively. Seventeen patients (56.7%) had no GVHD. Eleven patients (36.7%) developed grade II–III acute GVHD. Seven patients (23.3%) died of transplant-related toxicity, including fungal or viral infections and thrombotic microangiopathy, and four patients died of disease progression. Estimated relapse rate at 3 years was only 20.9%. The probability of survival at 3 years was 49.9%. Conclusions These data suggest that, in unmanipulated HLA-haploidentical allogeneic BMT, this GVHD prophylactic regimen, which includes methylprednisolone 2 mg/kg, and early therapeutic intervention for GVH reaction suppress the incidence of severe GVHD to an acceptable level, while preserving the graft-vs-leukemia effect.