Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution

Kunihisa Nakai, Shin Mineishi, Masahiro Kami, Takeshi Saito, Akiko Hori, Rie Kojima, Osamu Imataki, Tamae Hamaki, Satoshi Yoshihara, Mutsuko Ohnishi, Sung Won Kim, Toshihiko Ando, Arima Fumitoh, Yoshinobu Kanda, Atsushi Makimoto, Ryuji Tanosaki, Sachiyo Kanai, Yuji Heike, Toshihiro Ohnishi, Yoshifumi KawanoHiro Wakasugi, Yoichi Takaue

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background. There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). Methods. To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. Results. The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. Conclusions. We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.

Original languageEnglish (US)
Pages (from-to)2135-2143
Number of pages9
JournalTransplantation
Volume75
Issue number12
StatePublished - Jun 27 2003

Fingerprint

Chimerism
Antilymphocyte Serum
Stem Cell Transplantation
Graft vs Host Disease
Tissue Donors
Incidence
Transplantation
Bone Marrow
T-Lymphocytes
Conditioning (Psychology)
Cytomegalovirus Infections
Cell Lineage
Immunosuppressive Agents
Dendritic Cells
Leukemia
Multivariate Analysis
Transplants
Recurrence

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Nakai, Kunihisa ; Mineishi, Shin ; Kami, Masahiro ; Saito, Takeshi ; Hori, Akiko ; Kojima, Rie ; Imataki, Osamu ; Hamaki, Tamae ; Yoshihara, Satoshi ; Ohnishi, Mutsuko ; Kim, Sung Won ; Ando, Toshihiko ; Fumitoh, Arima ; Kanda, Yoshinobu ; Makimoto, Atsushi ; Tanosaki, Ryuji ; Kanai, Sachiyo ; Heike, Yuji ; Ohnishi, Toshihiro ; Kawano, Yoshifumi ; Wakasugi, Hiro ; Takaue, Yoichi. / Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution. In: Transplantation. 2003 ; Vol. 75, No. 12. pp. 2135-2143.
@article{8615f82d737248ef92d931476311a499,
title = "Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution",
abstract = "Background. There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). Methods. To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. Results. The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. Conclusions. We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.",
author = "Kunihisa Nakai and Shin Mineishi and Masahiro Kami and Takeshi Saito and Akiko Hori and Rie Kojima and Osamu Imataki and Tamae Hamaki and Satoshi Yoshihara and Mutsuko Ohnishi and Kim, {Sung Won} and Toshihiko Ando and Arima Fumitoh and Yoshinobu Kanda and Atsushi Makimoto and Ryuji Tanosaki and Sachiyo Kanai and Yuji Heike and Toshihiro Ohnishi and Yoshifumi Kawano and Hiro Wakasugi and Yoichi Takaue",
year = "2003",
month = "6",
day = "27",
language = "English (US)",
volume = "75",
pages = "2135--2143",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

Nakai, K, Mineishi, S, Kami, M, Saito, T, Hori, A, Kojima, R, Imataki, O, Hamaki, T, Yoshihara, S, Ohnishi, M, Kim, SW, Ando, T, Fumitoh, A, Kanda, Y, Makimoto, A, Tanosaki, R, Kanai, S, Heike, Y, Ohnishi, T, Kawano, Y, Wakasugi, H & Takaue, Y 2003, 'Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution', Transplantation, vol. 75, no. 12, pp. 2135-2143.

Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution. / Nakai, Kunihisa; Mineishi, Shin; Kami, Masahiro; Saito, Takeshi; Hori, Akiko; Kojima, Rie; Imataki, Osamu; Hamaki, Tamae; Yoshihara, Satoshi; Ohnishi, Mutsuko; Kim, Sung Won; Ando, Toshihiko; Fumitoh, Arima; Kanda, Yoshinobu; Makimoto, Atsushi; Tanosaki, Ryuji; Kanai, Sachiyo; Heike, Yuji; Ohnishi, Toshihiro; Kawano, Yoshifumi; Wakasugi, Hiro; Takaue, Yoichi.

In: Transplantation, Vol. 75, No. 12, 27.06.2003, p. 2135-2143.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution

AU - Nakai, Kunihisa

AU - Mineishi, Shin

AU - Kami, Masahiro

AU - Saito, Takeshi

AU - Hori, Akiko

AU - Kojima, Rie

AU - Imataki, Osamu

AU - Hamaki, Tamae

AU - Yoshihara, Satoshi

AU - Ohnishi, Mutsuko

AU - Kim, Sung Won

AU - Ando, Toshihiko

AU - Fumitoh, Arima

AU - Kanda, Yoshinobu

AU - Makimoto, Atsushi

AU - Tanosaki, Ryuji

AU - Kanai, Sachiyo

AU - Heike, Yuji

AU - Ohnishi, Toshihiro

AU - Kawano, Yoshifumi

AU - Wakasugi, Hiro

AU - Takaue, Yoichi

PY - 2003/6/27

Y1 - 2003/6/27

N2 - Background. There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). Methods. To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. Results. The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. Conclusions. We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.

AB - Background. There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). Methods. To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. Results. The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. Conclusions. We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.

UR - http://www.scopus.com/inward/record.url?scp=0038112141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038112141&partnerID=8YFLogxK

M3 - Article

C2 - 12829926

AN - SCOPUS:0038112141

VL - 75

SP - 2135

EP - 2143

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 12

ER -