Previous studies have suggested that tacrolimus (TAC) is more potent than cyclosporine (CSA) for prophylaxis against acute GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). However, the target blood concentrations of these drugs in these studies were not consistent with the current recommendations. Therefore, we performed a randomized controlled trial to compare CSA and TAC with target blood concentrations of 500 and 15 ng/ml, respectively, to prevent acute GVHD after unrelated HSCT. A total of 107 patients were randomized into a CSA group (n=53) or a TAC group (n=54). During the first 4 weeks after HSCT, more than 90% of the patients achieved a mean blood concentration of between 80 and 120% of the target concentration. The incidences of grade II–IV and grade III–IV acute GVHD were 39.6 and 7.5% for the CSA group and 33.3 and 9.4% for the TAC group, respectively (P=0.41 and P=0.76). Other clinical outcomes, including overall survival, disease-free survival and the incidences of relapse, non-relapse mortality, and organ toxicities, were also equivalent. We concluded that the combinations of CSA and TAC with strict dose adjustment showed similar efficacies and toxicities as prophylaxis against acute GVHD after unrelated HSCT.
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We thank the staffs at the participating centers, including Tokyo Medical University Hospital, Yokohama City University Medical Center, Jikei University Hospital and Yokohama City University Hospital. We also thank the staffs at the Japan Clinical Research Support Unit and the data center of the Kanto Study Group for Cell Therapy.
YK designed the study and analyzed the data. TK, TM, MT, CN, AY, RW, SK, KK, JK, ND, MA, S-IK, MK, HK and SO participated in the study and gathered the data. AT contributed as a data manager. YK wrote the first draft of the paper and all other authors contributed to the final version.
YK and CN received an honorarium and a research grant from Astellas Pharma Inc. and Novartis Pharma KK. SO received research a grant from Astellas Pharma Inc. Division of Hematology, Department of Medicine, Keio University School of Medicine had courses endowed by Novartis Pharmaceuticals.
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Kanda, Y., Kobayashi, T., Mori, T. et al. A randomized controlled trial of cyclosporine and tacrolimus with strict control of blood concentrations after unrelated bone marrow transplantation. Bone Marrow Transplant 51, 103–109 (2016). https://doi.org/10.1038/bmt.2015.222
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