CD8+ T cell dose affects development of acute graft-vs-host disease following reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation.
OBJECTIVE
Acute graft-vs-host disease (aGVHD) remains an important cause of morbidity after reduced-intensity conditioning (RIC) allogeneic transplantation (allo-SCT). It has been shown that antithymocyte globulin (ATG) dose infused during RIC is a major determinant for the likelihood of developing aGVHD. The ATG modulation on aGVHD is likely related to in vivo T-cell depletion.


METHODS
We therefore investigated the relationship between the cellular composition of the allograft and clinical outcome in 57 patients who received allogeneic peripheral blood stem cells from HLA-identical siblings following an ATG-based RIC.


RESULTS
In a multivariate analysis, the CD8+ T cell dose infused was the only parameter associated with the risk of aGVHD (p=0.031; RR=1.96; 95% CI, 1.1-3.6). When looking at the extremes, patients experiencing grade III-IV aGVHD received a median of 143 x 10(6)/kg CD8+ T cells, while patients without aGVHD received a median of 96 x 10(6)/kg CD8+ T cells (p=0.021). None of the different cell subtypes contained in the allograft was associated with a significant probability of developing chronic GVHD. Patients with grade II aGVHD who received an intermediate dose of CD8+ T cells (median, 111 x 10(6)/kg) had a significantly better overall survival in comparison to patients with grade 0-I or grade III-IV aGVHD (p=0.009).


CONCLUSIONS
In comparison to myeloablative allo-SCT, these results demonstrate that a cautious monitoring of the number of cells infused, at least in the context of ATG-based RIC, may represent an important predictive indicator of early transplant-related events and outcome after RIC allo-SCT.
Mohty
Mohamad
M
Unité de Transplantation et de Thérapie Cellulaire (UTTC), Institut Paoli-Calmettes, Marseille, France. mohtym@marseille.fnclcc.fr
Bagattini
Sophie
S
Chabannon
Christian
C
Faucher
Catherine
C
Bardou
Valerie-Jeanne
VJ
Bilger
Karin
K
Vey
Norbert
N
Gaugler
Béatrice
B
Stoppa
Anne-Marie
AM
Coso
Diane
D
Ladaique
Patrick
P
Olive
Daniel
D
Viens
Patrice
P
Blaise
Didier
D
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology*; D006801:Humans; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion / Q000592:standards*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000401:mortality / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome