TY - JOUR
T1 - Single-dose daily infusion of cyclosporine for prevention of graft-versus-host disease after allogeneic bone marrow transplantation from HLA allele-matched, unrelated donors
AU - Nawa, Yuichiro
AU - Hara, Masamichi
AU - Tanimoto, Kazushi
AU - Nakase, Koichi
AU - Kozuka, Teruhiko
AU - Maeda, Yoshinobu
PY - 2006/2
Y1 - 2006/2
N2 - Peak blood concentration of cyclosporine (CsA) in renal transplantation patients was recently reported to be associated with clinical efficacy. We therefore evaluated the toxicity and efficacy of a regimen of once-daily infusion of CsA plus a short course of methotrexate as prophylaxis of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation from an HLA allele-matched, unrelated donor. Nineteen patients with hematologic malignancies received CsA, 3 mg/kg per day, as a 4-hour intravenous (IV) infusion from day -1. After engraftment, patients received CsA orally at twice the IV dose. The CsA dose was adjusted to maintain the blood trough level between 150 and 200 ng/mL. Methotrexate was administered IV at doses of 10 mg/m2 on day 1 and 7 mg/m2 on days 3,6, and 11. Bone marrow engraftment occurred in all patients. Grade 1 and grade 2 GVHD occurred in 6 (31.6%) and 7 (36.8%) of the 19 patients, respectively. No patient had grade 3 or 4 GVHD. Acute nephrotoxicity developed in 1 (5.3%) of the 19 patients, and hypertension developed in 3 (15.8%) of the 19 patients. We evaluated the pharmacokinetics of 4-hour CsA infusion in 10 patients. The mean trough concentration, mean peak concentration, mean time to peak concentration, and area under the curve (24 hours) were 161 ± 43 ng/mL, 1498 ± 387 ng/mL, 3.2 ± 1.0 hours, and 10,848 ± 1,991 ng · h/mL, respectively. This regimen was well tolerated and did not enhance the risk of severe GVHD in patients undergoing allogeneic bone marrow transplantation from an HLA allele-matched, unrelated donor.
AB - Peak blood concentration of cyclosporine (CsA) in renal transplantation patients was recently reported to be associated with clinical efficacy. We therefore evaluated the toxicity and efficacy of a regimen of once-daily infusion of CsA plus a short course of methotrexate as prophylaxis of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation from an HLA allele-matched, unrelated donor. Nineteen patients with hematologic malignancies received CsA, 3 mg/kg per day, as a 4-hour intravenous (IV) infusion from day -1. After engraftment, patients received CsA orally at twice the IV dose. The CsA dose was adjusted to maintain the blood trough level between 150 and 200 ng/mL. Methotrexate was administered IV at doses of 10 mg/m2 on day 1 and 7 mg/m2 on days 3,6, and 11. Bone marrow engraftment occurred in all patients. Grade 1 and grade 2 GVHD occurred in 6 (31.6%) and 7 (36.8%) of the 19 patients, respectively. No patient had grade 3 or 4 GVHD. Acute nephrotoxicity developed in 1 (5.3%) of the 19 patients, and hypertension developed in 3 (15.8%) of the 19 patients. We evaluated the pharmacokinetics of 4-hour CsA infusion in 10 patients. The mean trough concentration, mean peak concentration, mean time to peak concentration, and area under the curve (24 hours) were 161 ± 43 ng/mL, 1498 ± 387 ng/mL, 3.2 ± 1.0 hours, and 10,848 ± 1,991 ng · h/mL, respectively. This regimen was well tolerated and did not enhance the risk of severe GVHD in patients undergoing allogeneic bone marrow transplantation from an HLA allele-matched, unrelated donor.
KW - CsA
KW - Graft-versus-host disease
KW - Matched unrelated donor
KW - Short infusion
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U2 - 10.1532/IJH97.05006
DO - 10.1532/IJH97.05006
M3 - Article
C2 - 16513536
AN - SCOPUS:33646825995
VL - 83
SP - 159
EP - 163
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 2
ER -