TY - JOUR
T1 - Beneficial role of CD8+T-cell reconstitution after HLA-haploidentical stem cell transplantation for high-risk acute leukaemias
T2 - results from a clinico-biological EBMT registry study mostly in the T-cell-depleted setting
AU - Bondanza, Attilio
AU - Ruggeri, Loredana
AU - Noviello, Maddalena
AU - Eikema, Dirk-Jan
AU - Bonini, Chiara
AU - Chabannon, Christian
AU - van der Werf, Steffie
AU - van Biezen, Anja
AU - de Wreede, Liesbeth C.
AU - Crucitti, Lara
AU - Vago, Luca
AU - Merluzzi, Mara
AU - Massei, Maria Speranza
AU - Veelken, Hendrik
AU - Koc, Yener
AU - Bader, Peter
AU - Gruhn, Bernd
AU - Locatelli, Franco
AU - Ciceri, Fabio
AU - Toubert, Antoine
AU - Velardi, Andrea
AU - Bernardo, Maria Ester
AU - Dazzi, Francesco
AU - Ellard, Rose
AU - Fleischhauer, Katharina
AU - Greco, Rafaella
AU - Hudecek, Michael
AU - Koehl, Ulrike
AU - Kuball, Jurgen
AU - Malard, Florent
AU - Pedrazzoli, Paolo
AU - Rocha, Vanderson
AU - Ruggeri, Annalisa
AU - Urbano-Ispizua, Alvaro
AU - Wang, Junfeng
AU - Wieten, Lotte
AU - EBMT Cell Therapy and Immunobiology Working Party
PY - 2019/6
Y1 - 2019/6
N2 - HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001-2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM). Negative prognostic factors for overall survival were advanced disease state at transplantation, host age and CMV seropositivity. Higher CD3, CD4 and CD8 counts were associated with a better overall survival and a lower NRM. Strikingly, when tested in multivariable analysis, higher CD3 and CD8 counts were still significantly associated with a lower NRM. These results indicate that an accelerated T-cell reconstitution correlates with less transplantation mortality, likely due to the protective role of T cells against viral infections. This observation suggests that CD8+ T-cell counts should be investigated as surrogate biomarkers of outcome in prospective haplo-HSCT trials.
AB - HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001-2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM). Negative prognostic factors for overall survival were advanced disease state at transplantation, host age and CMV seropositivity. Higher CD3, CD4 and CD8 counts were associated with a better overall survival and a lower NRM. Strikingly, when tested in multivariable analysis, higher CD3 and CD8 counts were still significantly associated with a lower NRM. These results indicate that an accelerated T-cell reconstitution correlates with less transplantation mortality, likely due to the protective role of T cells against viral infections. This observation suggests that CD8+ T-cell counts should be investigated as surrogate biomarkers of outcome in prospective haplo-HSCT trials.
KW - ADULTS
KW - BLOOD
KW - BONE-MARROW-TRANSPLANTATION
KW - COUNT
KW - DISEASE
KW - IMMUNOTHERAPY
KW - INDEX
KW - RECOVERY
KW - RESPONSES
KW - SCORE
KW - CHILDREN
U2 - 10.1038/s41409-018-0351-x
DO - 10.1038/s41409-018-0351-x
M3 - Article
C2 - 30531916
VL - 54
SP - 867
EP - 876
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 6
ER -