Unmanipulated HLA 2-3 antigen–mismatched (haploidentical) bone marrow transplantation using only pharmacological GVHD prophylaxis
Received 13 May 2007; received in revised form 30 July 2007; accepted 8 August 2007. published online 08 October 2007.
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/m2 × 4) with or without cytosine arabinoside (2 g/m2 × 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 × 109/L) and platelet (>20 × 109/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.
aDepartment of Molecular Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
bDivision of Multidisciplinary Radiotherapy, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
cDivision of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
dFirst Department of Surgery, Hyogo College of Medicine, Hyogo, Japan
Offprint requests to: Hiroyasu Ogawa, M.D., PhD., Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan 663-8501
ABSTRACT