Summary:
We retrospectively compared the incidence of acute graft-versus-host disease (GVHD) before and after September 1999, when we changed the mode of cyclosporine A (CsA) administration from twice-daily infusions (TD) (n=58) to continuous infusion (CIF) (n=71). The incidence of grade II–IV acute GVHD in the CIF group (56%) was significantly higher than that in the TD group (27%, P=0.00022). Multivariate analysis identified only two independent significant risk factors for the development of grade II–IV acute GVHD; CIF of CsA (relative risk 2.59, 95% CI 1.46–4.60, P=0.0011) and the presence of HLA mismatch (2.01, 95% CI 1.15–3.53, P=0.014). The incidence of relapse was significantly lower in the CIF group when adjusted for disease status before transplantation (0.41, 95% CI 0.18–0.95, P=0.038), which resulted in better disease-free survival in high-risk patients (43 vs 16% at 2 years, P=0.039), but not in standard-risk patients (72 vs 80%, P=0.45). CIF of CsA with a target level of 250–400 ng/ml may not be appropriate for GVHD prophylaxis in standard-risk patients.
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References
Ruutu T, Niederwieser D, Gratwohl A et al. A survey of the prophylaxis and treatment of acute GVHD in Europe: a report of the European Group for Blood and Marrow, Transplantation (EBMT). Chronic Leukaemia Working Party of the EBMT. Bone Marrow Transplant 1997; 19: 759–764.
Alvarez JS, Sacristan JA, Alsar MJ . Comparison of a monoclonal antibody fluorescent polarization immunoassay with monoclonal antibody radioimmunoassay for cyclosporin determination in whole blood. Ther Drug Monit 1992; 14: 78–80.
Thomas ED, Storb R, Clift RA et al. Bone-marrow transplantation (second of two parts). N Engl J Med 1975; 292: 895–902.
Kanda Y, Mineishi S, Saito T et al. Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogeneic hematopoietic stem cell transplantation: a single-center experience in Japan. Bone Marrow Transplant 2001; 27: 437–444.
Gooley TA, Leisenring W, Crowley J et al. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18: 695–706.
Nash RA, Antin JH, Karanes C et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood 2000; 96: 2062–2068.
Ratanatharathorn V, Nash RA, Przepiorka D et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 1998; 92: 2303–2314.
Miller KB, Schenkein DP, Comenzo R et al. Adjusted-dose continuous-infusion cyclosporin A to prevent graft-versus-host disease following allogeneic bone marrow transplantation. Ann Hematol 1994; 68: 15–20.
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This research was supported by a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor and Welfare.
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Ogawa, N., Kanda, Y., Matsubara, M. et al. Increased incidence of acute graft-versus-host disease with the continuous infusion of cyclosporine A compared to twice-daily infusion. Bone Marrow Transplant 33, 549–552 (2004). https://doi.org/10.1038/sj.bmt.1704374
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DOI: https://doi.org/10.1038/sj.bmt.1704374
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