Single-dose daily infusion of cyclosporine for prevention of graft-versus-host disease after allogeneic bone marrow transplantation from HLA allele-matched, unrelated donors

Yuichiro Nawa, Masamichi Hara, Kazushi Tanimoto, Koichi Nakase, Teruhiko Kozuka, Yoshinobu Maeda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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/m 2 on day 1 and 7 mg/m 2 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.

Original languageEnglish
Pages (from-to)159-163
Number of pages5
JournalInternational Journal of Hematology
Volume83
Issue number2
DOIs
Publication statusPublished - Feb 2006
Externally publishedYes

Fingerprint

Unrelated Donors
Homologous Transplantation
Graft vs Host Disease
Bone Marrow Transplantation
Cyclosporine
Alleles
Methotrexate
Hematologic Neoplasms
Intravenous Infusions
Kidney Transplantation
Area Under Curve
Pharmacokinetics
Bone Marrow
Hypertension

Keywords

  • CsA
  • Graft-versus-host disease
  • Matched unrelated donor
  • Short infusion

ASJC Scopus subject areas

  • Hematology

Cite this

Single-dose daily infusion of cyclosporine for prevention of graft-versus-host disease after allogeneic bone marrow transplantation from HLA allele-matched, unrelated donors. / Nawa, Yuichiro; Hara, Masamichi; Tanimoto, Kazushi; Nakase, Koichi; Kozuka, Teruhiko; Maeda, Yoshinobu.

In: International Journal of Hematology, Vol. 83, No. 2, 02.2006, p. 159-163.

Research output: Contribution to journalArticle

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abstract = "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/m 2 on day 1 and 7 mg/m 2 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.",
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