The safety and efficacy of acute graft-versus-host disease prophylaxis with a higher target blood concentration of cyclosporine around 500 ng/mL

Tomohito Machishima, Shinichi Kako, Hidenori Wada, Ryoko Yamasaki, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Masahiro Ashizawa, Kiriko Terasako, Shun ichi Kimura, Misato Kikuchi, Hideki Nakasone, Junya Kanda, Rie Yamazaki, Junji Nishida, Yoshinobu Kanda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Cyclosporine (CsA) is the most widely used immunosuppressive agent for the prevention of acute graft-versus-host disease (GVHD). In a previous report, the incidence of acute GVHD was decreased by increasing the target blood concentration of CsA during a continuous infusion from 300 to 500 ng/mL without excessive toxicities. To confirm these results, we retrospectively analyzed 69 patients who received a continuous infusion of CsA at a higher target CsA level between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with 29 patients who received CsA with a lower target concentration between 250 and 350 ng/mL (CsA300 group). The target concentration was determined based on the status of background diseases. Multivariate analysis revealed that the incidence of grade III-IV acute GVHD was significantly lower in the CsA500 group, although the incidence of grade II-IV acute GVHD was not different. Toxicities were equivalently observed between the two groups. Concomitant administration of voriconazole or itraconazole and higher hematocrit were identified as independent significant factors for higher concentration/dose ratio of CsA. The average dose of CsA to maintain CsA level around 500 ng/mL was higher compared with the previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the difference in measuring method of CsA concentration. We conclude that continuous infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and effective GVHD prophylaxis, but caution should be paid for the difference in measuring method.

Original languageEnglish
Pages (from-to)749-756
Number of pages8
JournalClinical Transplantation
Volume27
Issue number5
DOIs
Publication statusPublished - 2013 Sep 1
Externally publishedYes

Fingerprint

Graft vs Host Disease
Cyclosporine
Safety
Incidence
Itraconazole
Immunosuppressive Agents
Hematocrit
Multivariate Analysis

Keywords

  • Acute graft-versus-host disease
  • Allogeneic hematopoietic stem cell transplantation
  • Cyclosporine
  • Target level

ASJC Scopus subject areas

  • Transplantation

Cite this

The safety and efficacy of acute graft-versus-host disease prophylaxis with a higher target blood concentration of cyclosporine around 500 ng/mL. / Machishima, Tomohito; Kako, Shinichi; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Ashizawa, Masahiro; Terasako, Kiriko; Kimura, Shun ichi; Kikuchi, Misato; Nakasone, Hideki; Kanda, Junya; Yamazaki, Rie; Nishida, Junji; Kanda, Yoshinobu.

In: Clinical Transplantation, Vol. 27, No. 5, 01.09.2013, p. 749-756.

Research output: Contribution to journalArticle

Machishima, T, Kako, S, Wada, H, Yamasaki, R, Ishihara, Y, Kawamura, K, Sakamoto, K, Sato, M, Ashizawa, M, Terasako, K, Kimura, SI, Kikuchi, M, Nakasone, H, Kanda, J, Yamazaki, R, Nishida, J & Kanda, Y 2013, 'The safety and efficacy of acute graft-versus-host disease prophylaxis with a higher target blood concentration of cyclosporine around 500 ng/mL', Clinical Transplantation, vol. 27, no. 5, pp. 749-756. https://doi.org/10.1111/ctr.12213
Machishima, Tomohito ; Kako, Shinichi ; Wada, Hidenori ; Yamasaki, Ryoko ; Ishihara, Yuko ; Kawamura, Koji ; Sakamoto, Kana ; Sato, Miki ; Ashizawa, Masahiro ; Terasako, Kiriko ; Kimura, Shun ichi ; Kikuchi, Misato ; Nakasone, Hideki ; Kanda, Junya ; Yamazaki, Rie ; Nishida, Junji ; Kanda, Yoshinobu. / The safety and efficacy of acute graft-versus-host disease prophylaxis with a higher target blood concentration of cyclosporine around 500 ng/mL. In: Clinical Transplantation. 2013 ; Vol. 27, No. 5. pp. 749-756.
@article{92db521e97c04f7bba5991e5c3355e61,
title = "The safety and efficacy of acute graft-versus-host disease prophylaxis with a higher target blood concentration of cyclosporine around 500 ng/mL",
abstract = "Cyclosporine (CsA) is the most widely used immunosuppressive agent for the prevention of acute graft-versus-host disease (GVHD). In a previous report, the incidence of acute GVHD was decreased by increasing the target blood concentration of CsA during a continuous infusion from 300 to 500 ng/mL without excessive toxicities. To confirm these results, we retrospectively analyzed 69 patients who received a continuous infusion of CsA at a higher target CsA level between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with 29 patients who received CsA with a lower target concentration between 250 and 350 ng/mL (CsA300 group). The target concentration was determined based on the status of background diseases. Multivariate analysis revealed that the incidence of grade III-IV acute GVHD was significantly lower in the CsA500 group, although the incidence of grade II-IV acute GVHD was not different. Toxicities were equivalently observed between the two groups. Concomitant administration of voriconazole or itraconazole and higher hematocrit were identified as independent significant factors for higher concentration/dose ratio of CsA. The average dose of CsA to maintain CsA level around 500 ng/mL was higher compared with the previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the difference in measuring method of CsA concentration. We conclude that continuous infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and effective GVHD prophylaxis, but caution should be paid for the difference in measuring method.",
keywords = "Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplantation, Cyclosporine, Target level",
author = "Tomohito Machishima and Shinichi Kako and Hidenori Wada and Ryoko Yamasaki and Yuko Ishihara and Koji Kawamura and Kana Sakamoto and Miki Sato and Masahiro Ashizawa and Kiriko Terasako and Kimura, {Shun ichi} and Misato Kikuchi and Hideki Nakasone and Junya Kanda and Rie Yamazaki and Junji Nishida and Yoshinobu Kanda",
year = "2013",
month = "9",
day = "1",
doi = "10.1111/ctr.12213",
language = "English",
volume = "27",
pages = "749--756",
journal = "Clinical Transplantation",
issn = "0902-0063",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - The safety and efficacy of acute graft-versus-host disease prophylaxis with a higher target blood concentration of cyclosporine around 500 ng/mL

AU - Machishima, Tomohito

AU - Kako, Shinichi

AU - Wada, Hidenori

AU - Yamasaki, Ryoko

AU - Ishihara, Yuko

AU - Kawamura, Koji

AU - Sakamoto, Kana

AU - Sato, Miki

AU - Ashizawa, Masahiro

AU - Terasako, Kiriko

AU - Kimura, Shun ichi

AU - Kikuchi, Misato

AU - Nakasone, Hideki

AU - Kanda, Junya

AU - Yamazaki, Rie

AU - Nishida, Junji

AU - Kanda, Yoshinobu

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Cyclosporine (CsA) is the most widely used immunosuppressive agent for the prevention of acute graft-versus-host disease (GVHD). In a previous report, the incidence of acute GVHD was decreased by increasing the target blood concentration of CsA during a continuous infusion from 300 to 500 ng/mL without excessive toxicities. To confirm these results, we retrospectively analyzed 69 patients who received a continuous infusion of CsA at a higher target CsA level between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with 29 patients who received CsA with a lower target concentration between 250 and 350 ng/mL (CsA300 group). The target concentration was determined based on the status of background diseases. Multivariate analysis revealed that the incidence of grade III-IV acute GVHD was significantly lower in the CsA500 group, although the incidence of grade II-IV acute GVHD was not different. Toxicities were equivalently observed between the two groups. Concomitant administration of voriconazole or itraconazole and higher hematocrit were identified as independent significant factors for higher concentration/dose ratio of CsA. The average dose of CsA to maintain CsA level around 500 ng/mL was higher compared with the previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the difference in measuring method of CsA concentration. We conclude that continuous infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and effective GVHD prophylaxis, but caution should be paid for the difference in measuring method.

AB - Cyclosporine (CsA) is the most widely used immunosuppressive agent for the prevention of acute graft-versus-host disease (GVHD). In a previous report, the incidence of acute GVHD was decreased by increasing the target blood concentration of CsA during a continuous infusion from 300 to 500 ng/mL without excessive toxicities. To confirm these results, we retrospectively analyzed 69 patients who received a continuous infusion of CsA at a higher target CsA level between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with 29 patients who received CsA with a lower target concentration between 250 and 350 ng/mL (CsA300 group). The target concentration was determined based on the status of background diseases. Multivariate analysis revealed that the incidence of grade III-IV acute GVHD was significantly lower in the CsA500 group, although the incidence of grade II-IV acute GVHD was not different. Toxicities were equivalently observed between the two groups. Concomitant administration of voriconazole or itraconazole and higher hematocrit were identified as independent significant factors for higher concentration/dose ratio of CsA. The average dose of CsA to maintain CsA level around 500 ng/mL was higher compared with the previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the difference in measuring method of CsA concentration. We conclude that continuous infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and effective GVHD prophylaxis, but caution should be paid for the difference in measuring method.

KW - Acute graft-versus-host disease

KW - Allogeneic hematopoietic stem cell transplantation

KW - Cyclosporine

KW - Target level

UR - http://www.scopus.com/inward/record.url?scp=84884985659&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884985659&partnerID=8YFLogxK

U2 - 10.1111/ctr.12213

DO - 10.1111/ctr.12213

M3 - Article

C2 - 24033855

AN - SCOPUS:84884985659

VL - 27

SP - 749

EP - 756

JO - Clinical Transplantation

JF - Clinical Transplantation

SN - 0902-0063

IS - 5

ER -