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.

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Additional information

Members of the EBMT Cell Therapy and Immunobiology Working Party are listed below Acknowledgements.

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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’).

EBMT Cell Therapy and Immunobiology Working Party

Maria Ester Bernardo; IRCCS San Raffaele Scientific Institute, Milan, Italy. Francesco Dazzi; GKT School of Medicine, London, UK. Dirk-Jan Eikema; EBMT Dataoffice Leiden, Leiden, The Netherlands. Rose Ellard; King’s College, London, UK. Katharina Fleischhauer; University Hospital Essen, Essen, Germany. Rafaella Greco; IRCCS San Raffaele Scientific Institute, Milan, Italy. Michael Hudecek; University Hospital Würzburg, Würzburg, Germany. Ulrike Köhl; Hannover Medical School, Hannover, Germany. Jürgen Kuball; University Medical Centre Utrecht, Utrecht, The Netherlands. Florent Malard; Hospital Saint Antoine, Paris, France. Paolo Pedrazzoli; Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Vanderson Rocha; Hospital Sirio-Libanes, Sao Paulo, Brazil. Annalisa Ruggeri; IRRCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. Álvaro Urbano-Ispizua; Hospital Clinic Barcelona, Barcelona, Spain. Junfeng Wang; EBMT Dataoffice Leiden, Leiden, The Netherlands. Lotte Wieten; Maastricht University Medical Centre, Maastricht, The Netherlands.

Author contributions

AB, LR and MN designed the study, analysed data and wrote the manuscript; CB designed the study, analysed data and revised the manuscript; LV, LC and FC provided data from San Raffaele University Hospital; MM and MSM provided data from Perugia University Hospital; HV provided data from Leiden University Medical Centre; YK provided data from Antalya Medical Hospital; PB provided data from Frankfurt University Hospital; BG provided data from Jena University Hospital; FL provided data from Ospedale Pediatrico Bambino Gesù and extensively reviewed the manuscript; SW and A van Biezen managed data; DJE and LdW performed statistical analysis and revised the manuscript; AT and CB revised the manuscript; AV designed the study, provided and analysed data and revised the manuscript.

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Affiliations

  1. San Raffaele University Hospital and Scientific Institute, Milan, Italy

    • Attilio Bondanza
    • , Maddalena Noviello
    • , Chiara Bonini
    • , Luca Vago
    •  & Fabio Ciceri
  2. Perugia General Hospital and University, Perugia, Italy

    • Loredana Ruggeri
    • , Mara Merluzzi
    • , Maria Speranza Massei
    •  & Andrea Velardi
  3. Leiden University Medical Center, Leiden, Netherlands

    • Dirk-Jan Eikema
    • , Steffie van der Werf
    • , Anja van Biezen
    • , Liesbeth C. de Wreede
    •  & Hendrik Veelken
  4. Institut Paoli-Calmettes and Inserm CBT-1409, Marseille, France

    • Christian Chabannon
  5. University of Milan, Milan, Italy

    • Lara Crucitti
  6. Medical Park Hospitals, Antalya, Turkey

    • Yener Koc
  7. University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany

    • Peter Bader
  8. Jena University Hospital, Jena, Germany

    • Bernd Gruhn
  9. IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

    • Franco Locatelli
  10. University of Pavia, Pavia, Italy

    • Franco Locatelli
  11. Hôpital Saint-Louis, Paris, France

    • Antoine Toubert

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    Correspondence to Attilio Bondanza.

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    https://doi.org/10.1038/s41409-018-0351-x