Increased incidence of acute graft-versus-host disease with the continuous infusion of cyclosporine A compared to twice-daily infusion

doi:doi:10.1038/sj.bmt.1704374

Bone Marrow Transplantation (2004) 33, 549–552. doi:10.1038/sj.bmt.1704374

Increased incidence of acute graft-versus-host disease with the continuous infusion of cyclosporine A compared to twice-daily infusion

N Ogawa¹, Y Kanda¹, M Matsubara¹, Y Asano¹, M Nakagawa¹, M Sakata-Yanagimoto¹, K Kandabashi¹, K Izutsu¹, Y Imai¹, A Hangaishi¹, M Kurokawa¹, S Tsujino¹, S Ogawa¹, K Aoki¹, S Chiba¹, T Motokura¹ and H Hirai¹

¹Department of Cell Therapy and Transplantation Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan

Correspondence: Dr Y Kanda, Department of Cell Therapy and Transplantation Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: ycanda@umin.ac.jp

Received 9 April 2003; Accepted 5 July 2003; Published online 12 January 2004.

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Abstract

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.