Effect of Early Posttransplantation Tacrolimus Concentration on the Development of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation fromUnrelated Donors

Takehiko Mori, Jun Kato, Takayuki Shimizu, Yoshinobu Aisa, Tomonori Nakazato, Akiko Yamane, Yukako Ono, Hiroyoshi Kunimoto, Shinichiro Okamoto

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Only limited data are available regarding the relationship between blood concentration of tacrolimus and its efficacy in preventing acute graft-versus-host disease (aGVHD). We retrospectively evaluated the effects of the whole blood concentration of tacrolimus, which was measured by an automated microparticle enzyme immunoassay, early after allogeneic hematopoietic stem cell transplantation (HSCT) upon the development of aGVHD. Sixty patients, who underwent allogeneic HSCT from serologically human-leukocyte antigen-matched unrelated donors and received continuous infusion of tacrolimus with short-term methotrexate for GVHD prophylaxis, were included in this study. The target range of the blood concentration of tacrolimus was set at 10 to 20 ng/mL, and the level was maintained within this range in all patients. However, the mean blood concentration of tacrolimus during the third week after HSCT was significantly associated with the grades of aGVHD (17.3 ± 2.1 in patients with grades 0-I vs 15.9 ± 2.8 in II-IV and 14.8 ± 2.1 in III-IV; P < .05 and <.01, respectively). Multivariate analysis also demonstrated that higher age (≥35) of donor(odds ratio [OR] = 4.28) and lower mean blood concentrations of tacrolimus during the second (OR = 0.75; 95% confidence interval [CI]: 0.58-0.98) and third weeks (OR = 0.76; 95% CI: 0.58-0.98) after HSCT were significant risk factors for grades II-IV aGVHD (P < .05). We conclude that the early posttransplantation blood concentration of tacrolimus had a significant impact on the development of moderate-to-severe aGVHD after allogeneic HSCT from an unrelated donor.

Original languageEnglish
Pages (from-to)229-234
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume18
Issue number2
DOIs
Publication statusPublished - 2012 Feb

Fingerprint

Hematopoietic Stem Cell Transplantation
Tacrolimus
Graft vs Host Disease
Tissue Donors
Unrelated Donors
Odds Ratio
Confidence Intervals
HLA Antigens
Immunoenzyme Techniques
Methotrexate
Multivariate Analysis

Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Blood concentration
  • Graft-versus-host disease
  • Tacrolimus
  • Unrelated donor

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

@article{6f8e6017bf0d4c94af557b5be0204bb5,
title = "Effect of Early Posttransplantation Tacrolimus Concentration on the Development of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation fromUnrelated Donors",
abstract = "Only limited data are available regarding the relationship between blood concentration of tacrolimus and its efficacy in preventing acute graft-versus-host disease (aGVHD). We retrospectively evaluated the effects of the whole blood concentration of tacrolimus, which was measured by an automated microparticle enzyme immunoassay, early after allogeneic hematopoietic stem cell transplantation (HSCT) upon the development of aGVHD. Sixty patients, who underwent allogeneic HSCT from serologically human-leukocyte antigen-matched unrelated donors and received continuous infusion of tacrolimus with short-term methotrexate for GVHD prophylaxis, were included in this study. The target range of the blood concentration of tacrolimus was set at 10 to 20 ng/mL, and the level was maintained within this range in all patients. However, the mean blood concentration of tacrolimus during the third week after HSCT was significantly associated with the grades of aGVHD (17.3 ± 2.1 in patients with grades 0-I vs 15.9 ± 2.8 in II-IV and 14.8 ± 2.1 in III-IV; P < .05 and <.01, respectively). Multivariate analysis also demonstrated that higher age (≥35) of donor(odds ratio [OR] = 4.28) and lower mean blood concentrations of tacrolimus during the second (OR = 0.75; 95{\%} confidence interval [CI]: 0.58-0.98) and third weeks (OR = 0.76; 95{\%} CI: 0.58-0.98) after HSCT were significant risk factors for grades II-IV aGVHD (P < .05). We conclude that the early posttransplantation blood concentration of tacrolimus had a significant impact on the development of moderate-to-severe aGVHD after allogeneic HSCT from an unrelated donor.",
keywords = "Allogeneic hematopoietic stem cell transplantation, Blood concentration, Graft-versus-host disease, Tacrolimus, Unrelated donor",
author = "Takehiko Mori and Jun Kato and Takayuki Shimizu and Yoshinobu Aisa and Tomonori Nakazato and Akiko Yamane and Yukako Ono and Hiroyoshi Kunimoto and Shinichiro Okamoto",
year = "2012",
month = "2",
doi = "10.1016/j.bbmt.2011.06.008",
language = "English",
volume = "18",
pages = "229--234",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Effect of Early Posttransplantation Tacrolimus Concentration on the Development of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation fromUnrelated Donors

AU - Mori, Takehiko

AU - Kato, Jun

AU - Shimizu, Takayuki

AU - Aisa, Yoshinobu

AU - Nakazato, Tomonori

AU - Yamane, Akiko

AU - Ono, Yukako

AU - Kunimoto, Hiroyoshi

AU - Okamoto, Shinichiro

PY - 2012/2

Y1 - 2012/2

N2 - Only limited data are available regarding the relationship between blood concentration of tacrolimus and its efficacy in preventing acute graft-versus-host disease (aGVHD). We retrospectively evaluated the effects of the whole blood concentration of tacrolimus, which was measured by an automated microparticle enzyme immunoassay, early after allogeneic hematopoietic stem cell transplantation (HSCT) upon the development of aGVHD. Sixty patients, who underwent allogeneic HSCT from serologically human-leukocyte antigen-matched unrelated donors and received continuous infusion of tacrolimus with short-term methotrexate for GVHD prophylaxis, were included in this study. The target range of the blood concentration of tacrolimus was set at 10 to 20 ng/mL, and the level was maintained within this range in all patients. However, the mean blood concentration of tacrolimus during the third week after HSCT was significantly associated with the grades of aGVHD (17.3 ± 2.1 in patients with grades 0-I vs 15.9 ± 2.8 in II-IV and 14.8 ± 2.1 in III-IV; P < .05 and <.01, respectively). Multivariate analysis also demonstrated that higher age (≥35) of donor(odds ratio [OR] = 4.28) and lower mean blood concentrations of tacrolimus during the second (OR = 0.75; 95% confidence interval [CI]: 0.58-0.98) and third weeks (OR = 0.76; 95% CI: 0.58-0.98) after HSCT were significant risk factors for grades II-IV aGVHD (P < .05). We conclude that the early posttransplantation blood concentration of tacrolimus had a significant impact on the development of moderate-to-severe aGVHD after allogeneic HSCT from an unrelated donor.

AB - Only limited data are available regarding the relationship between blood concentration of tacrolimus and its efficacy in preventing acute graft-versus-host disease (aGVHD). We retrospectively evaluated the effects of the whole blood concentration of tacrolimus, which was measured by an automated microparticle enzyme immunoassay, early after allogeneic hematopoietic stem cell transplantation (HSCT) upon the development of aGVHD. Sixty patients, who underwent allogeneic HSCT from serologically human-leukocyte antigen-matched unrelated donors and received continuous infusion of tacrolimus with short-term methotrexate for GVHD prophylaxis, were included in this study. The target range of the blood concentration of tacrolimus was set at 10 to 20 ng/mL, and the level was maintained within this range in all patients. However, the mean blood concentration of tacrolimus during the third week after HSCT was significantly associated with the grades of aGVHD (17.3 ± 2.1 in patients with grades 0-I vs 15.9 ± 2.8 in II-IV and 14.8 ± 2.1 in III-IV; P < .05 and <.01, respectively). Multivariate analysis also demonstrated that higher age (≥35) of donor(odds ratio [OR] = 4.28) and lower mean blood concentrations of tacrolimus during the second (OR = 0.75; 95% confidence interval [CI]: 0.58-0.98) and third weeks (OR = 0.76; 95% CI: 0.58-0.98) after HSCT were significant risk factors for grades II-IV aGVHD (P < .05). We conclude that the early posttransplantation blood concentration of tacrolimus had a significant impact on the development of moderate-to-severe aGVHD after allogeneic HSCT from an unrelated donor.

KW - Allogeneic hematopoietic stem cell transplantation

KW - Blood concentration

KW - Graft-versus-host disease

KW - Tacrolimus

KW - Unrelated donor

UR - http://www.scopus.com/inward/record.url?scp=84855595496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855595496&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2011.06.008

DO - 10.1016/j.bbmt.2011.06.008

M3 - Article

VL - 18

SP - 229

EP - 234

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 2

ER -