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.
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.
Nakai
Kunihisa
K
Stem Cell Transplant Unit, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Mineishi
Shin
S
Kami
Masahiro
M
Saito
Takeshi
T
Hori
Akiko
A
Kojima
Rie
R
Imataki
Osamu
O
Hamaki
Tamae
T
Yoshihara
Satoshi
S
Ohnishi
Mutsuko
M
Kim
Sung-Won
SW
Ando
Toshihiko
T
Fumitoh
Arima
A
Kanda
Yoshinobu
Y
Makimoto
Atsushi
A
Tanosaki
Ryuji
R
Kanai
Sachiyo
S
Heike
Yuji
Y
Ohnishi
Toshihiro
T
Kawano
Yoshifumi
Y
Wakasugi
Hiro
H
Takaue
Yoichi
Y
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology; D000069585:Filgrastim; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008875:Middle Aged; D011994:Recombinant Proteins; D033581:Stem Cell Transplantation; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim