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Prognostic factors for neutrophil engraftment after haploidentical cell transplantation with PT-Cy in patients with acute myeloid leukemia in complete remission, on behalf of the ALWP-EBMT

Bone Marrow Transplantation volume 56, pages 1842–1849 (2021)Cite this article

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Abstract

The use of haplo-HCT with posttransplant cyclophosphamide (PT-Cy) is a new standard in the treatment of hematological diseases. A paucity of data exists on risk factors for engraftment failure in haplo-HCT with PT-Cy. We analyzed 1939 adults with acute myeloid leukemia (AML) who received a first haplo-HCT from 2010 to 2019. Status at haplo-HCT was first complete remission (CR1) in 72.5% of patients, secondary AML was reported in 9.9%. Median follow-up was 24.4 months and median age at haplo-HCT was 51 years. Stem cell source was bone marrow (BM) in 42% and peripheral blood stem cell (PBSC) in 58%, and 64% of patients received a myeloablative conditioning (MAC) regimen. Cumulative incidence of primary graft failure (GF) was 6%; GF was reported in 110 patients and 54 died before day +30 with no sign of cell recovery. Overall, 33 patients underwent a second HCT in a median time of 45 days and 13 were alive at last follow-up, the 2-year overall survival (OS) after second HCT being 32.4%. In multivariate analysis, factors independently associated with the risk of nonengraftment were: secondary AML (HR 1.30, p = 0.003), use of RIC (HR 1.22, p < 0.001), and use of BM (HR 1.21, p < 0.001). At 2 years, leukemia-free survival (LFS) and OS for the entire population was 55.2% (95% CI: 52.6–57.6) and 60.9% (95% CI: 58.4–63.3), respectively. Incidence of GF after haplo-HCT with PT-Cy is lower than reported T-cell-depleted haplo-HCT. Optimization of conditioning regimen and graft source should be considered for reducing the risk of GF in haplo-HCT recipients using PT-Cy.

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Fig. 1: Cumulative incidence of neutrophil engraftment.

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Acknowledgements

The authors would like to thank Emmanuelle Polge from the office of the ALWP of the EBMT. The authors would also like to thank the clinical staff and investigators involved in this research and especially thank the patients who took part.

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Authors and Affiliations

  1. Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Annalisa Ruggeri & Fabio Ciceri

  2. Department of Haematology and EBMT Paris Study Office/CEREST-TC, Saint Antoine Hospital, Paris, France

    Myriam Labopin & Mohamad Mohty

  3. Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Emanuele Angelucci

  4. Department of Hematology, Institute Paoli-Calmettes, Marseille, France

    Didier Blaise

  5. Medicana International, Istanbul, Turkey

    Yener Koc

  6. Istituto di Ematologia, Fondazione Policlinico Universitario Gemelli, IRCCS, Roma, Italy

    Patrizia Chiusolo

  7. Haematology and Haemotherapy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Jose Luiz Diez-Martin

  8. Bone Marrow Transplantation Department, Anadolu Medical Center Hospital, Kocaeli, Turkey

    Zafer Gülbas

  9. Department of Hematology, Humanitas Clinical and Research Center, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano, Italy

    Luca Castagna

  10. SSCVD Trapianto di Cellule Staminali, AOU Città della Salute e della Scienza di Torino, Turin, Italy

    Benedetto Bruno

  11. Hematopoietic SCT Unit, Florence Nightingale Sisli Hospital, Istanbul, Turkey

    Mutlu Arat

  12. Stem Cell Transplant and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano, Bianchi-Melacrino-Morelli, Reggio Calabria, Italy

    Massimo Martino

  13. Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Arnon Nagler

  14. Sorbonne University and INSERM UMRs 938, Paris, France

    Mohamad Mohty

Authors
  1. Annalisa Ruggeri
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  2. Myriam Labopin
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  3. Emanuele Angelucci
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  4. Didier Blaise
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  5. Fabio Ciceri
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  7. Patrizia Chiusolo
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  8. Jose Luiz Diez-Martin
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  9. Zafer Gülbas
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  10. Luca Castagna
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  11. Benedetto Bruno
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  14. Arnon Nagler
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  15. Mohamad Mohty
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Contributions

A.R., A.N., and M.Mo. designed the study, M.L. performed the statistical analysis, A.R. wrote the manuscript, and E.A., D.B., F.C., Y.K., P.C., J.L.D.-M., Z.G., L.C., B.B., M.A., and M.Ma. were the principal investigators at the centers recruiting the highest number of patients for the study. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Annalisa Ruggeri.

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Ruggeri, A., Labopin, M., Angelucci, E. et al. Prognostic factors for neutrophil engraftment after haploidentical cell transplantation with PT-Cy in patients with acute myeloid leukemia in complete remission, on behalf of the ALWP-EBMT. Bone Marrow Transplant 56, 1842–1849 (2021). https://doi.org/10.1038/s41409-021-01248-3

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