Beneficial role of CD8+T-cell reconstitution after HLA-haploidentical stem cell transplantation for high-risk acute leukaemias: results from a clinico-biological EBMT registry study mostly in the T-cell-depleted setting

Attilio Bondanza*, Loredana Ruggeri, Maddalena Noviello, Dirk-Jan Eikema, Chiara Bonini, Christian Chabannon, Steffie van der Werf, Anja van Biezen, Liesbeth C. de Wreede, Lara Crucitti, Luca Vago, Mara Merluzzi, Maria Speranza Massei, Hendrik Veelken, Yener Koc, Peter Bader, Bernd Gruhn, Franco Locatelli, Fabio Ciceri, Antoine ToubertAndrea Velardi, Maria Ester Bernardo, Francesco Dazzi, Rose Ellard, Katharina Fleischhauer, Rafaella Greco, Michael Hudecek, Ulrike Koehl, Jurgen Kuball, Florent Malard, Paolo Pedrazzoli, Vanderson Rocha, Annalisa Ruggeri, Alvaro Urbano-Ispizua, Junfeng Wang, Lotte Wieten, EBMT Cell Therapy and Immunobiology Working Party

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)867-876
Number of pages10
JournalBone Marrow Transplantation
Volume54
Issue number6
DOIs
Publication statusPublished - Jun 2019

Keywords

  • ADULTS
  • BLOOD
  • BONE-MARROW-TRANSPLANTATION
  • COUNT
  • DISEASE
  • IMMUNOTHERAPY
  • INDEX
  • RECOVERY
  • RESPONSES
  • SCORE
  • CHILDREN

Cite this