Increased incidence of acute graft-versus-host disease with the continuous infusion of cyclosporine A compared to twice-daily infusion.
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.
Ogawa
N
N
Department of Cell Therapy and Transplantation Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Kanda
Y
Y
Matsubara
M
M
Asano
Y
Y
Nakagawa
M
M
Sakata-Yanagimoto
M
M
Kandabashi
K
K
Izutsu
K
K
Imai
Y
Y
Hangaishi
A
A
Kurokawa
M
M
Tsujino
S
S
Ogawa
S
S
Aoki
K
K
Chiba
S
S
Motokura
T
T
Hirai
H
H
D000208:Acute Disease; D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015994:Incidence; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000453:epidemiology; D007938:Leukemia / Q000453:epidemiology / Q000628:therapy*; D008297:Male; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine