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
N1 - Funding Information:
Acknowledgements We thank Dimitris Ziagkos for his contribution to the statistical analysis. This work was performed on behalf of the EBMT Cellular Therapy and Immunobiology Working Party. AB and AV have received specific funding from the Italian Ministry of Health through the Transcan Project Haplo-Immune. FL was supported by a specific grant from AIRC (‘Special grant 5 × 1.000’).
Publisher Copyright:
© 2018, Springer Nature Limited.
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
SN - 0268-3369
VL - 54
SP - 867
EP - 876
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 6
ER -