Favorable outcomes of tacrolimus compared with cyclosporine A for GVHD prophylaxis in HSCT for standard-risk hematological diseases.

Ryo Nasu, Yasuhito Nannya, Akihito Shinohara, Motoshi Ichikawa, Mineo Kurokawa

Index: Ann. Hematol. 93(7) , 1215-23, (2014)

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Abstract

Although calcineurin inhibitors (CNIs) with short-term methotrexate (stMTX) constitute standard prophylaxis for graft-versus-host diseases (GVHD) in hematopoietic stem cell transplantations (HSCT), comparative efficacy of cyclosporine A (CsA) and tacrolimus (Tac) still remains unclear. We have altered GVHD prophylaxis for standard-risk hematological malignancies from CsA (target trough level, 500 ng/mL) to Tac (15 ng/mL) both with stMTX in May 2008, enabling us to compare the efficacy of CNIs with little selection biases. The cumulative incidence of acute and chronic GVHD was comparable for CsA and Tac. Among the GVHD low-risk patients who received stem cells from matched sibling donors or cord blood, the Tac arm had a trend for favorable control of grade III-IV acute GVHD (6.7 vs. 30.0 %, p = 0.2), which may contribute to the significantly better overall survival (p = 0.048) and relapse-free survival (p = 0.043) in that group. Inadequate concentration of CNIs in early phase of HSCT affected the cumulative incidence of acute GVHD in the CsA but not in the Tac arm. There were no differences in the GVHD incidence and survival outcomes between CsA and Tac in the GVHD high-risk subgroup. This study underlies the significance of maintaining adequate CsA concentration in standard-risk HSCT.