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The role of HLA matching in unrelated donor hematopoietic stem cell transplantation for sickle cell disease in Europe

Bone Marrow Transplantation volume 55, pages 1946–1954 (2020)Cite this article

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Abstract

We report the results of an analysis of unrelated allogeneic hematopoietic stem cell transplantations (HSCT) in 71 patients with sickle cell disease (SCD) transplanted in EBMT centers between 2005 and 2017. Median age was 9.3 years; graft type was bone marrow in 79% and peripheral blood in 21%. Recipient–donor HLA match at high resolution typing was 10/10 in 31, 9/10 in 20, and 8/10 in 4 patients; the other patients had intermediate resolution typing. The most frequent conditioning regimens were fludarabine–thiotepa–treosulfan (64%) or busulfan–cyclophosphamide (12%). Cumulative incidence of neutrophil engraftment was 92%; platelet engraftment was 90%. Eleven patients (15%) experienced graft failure. Grade II–IV acute graft-vs.-host disease (GvHD) was 23%; 3-year chronic GvHD was 23%. Three-year overall survival (OS) was 88 ± 4%. GRFS was 62 ± 6%. HLA matching was the most significant risk factor for OS: 3-year OS was 96 ± 4% in 10/10 group vs. 75 ± 10% in 9–8/10 (p = 0.042); GRFS was 69 ± 9% vs. 50 ± 12% (p = 0.114), respectively. In conclusion, unrelated donor HSCT is a valid option for SCD patients who lack an HLA-identical sibling donor, preferably in the context of clinical trials. Using a 10/10 HLA-matched unrelated donor yields better survival indicating that HLA matching is an important donor selection factor in this nonmalignant disease.

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Fig. 1: Three-year overall survival (3y-OS).

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Acknowledgements

We thank Arnaud Dalissier from the EBMT for helping collecting and preparing the data, the EBMT centers who collaborated in updating the database, patients and families. We thank Monaco Government, the “Centre Scientifique de Monaco” and the association “Cordons de vie” who supported this work. We also thank all the participating transplant centers below: Austria: St. Anna Kinderspital, Vienna. Belgium: University Hospital Gasthuisberg, Leuven. France: Centre Hospitalier Universitaire Pontchaillou, Rennes. Germany: Medical School Hannover, Hannover; Dr. von Haunersches University Children’s Hospital, Munich; University of Regensburg, Regensburg; Klinikum der Johann-Wolfgang Goethe Universitaet, Frankfurt am Main; Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Ulm; Klinik Hamatologie/Onkologie, Idar-Oberstein; University Hospital Erlangen, Erlangen; Tübingen University Hospital, Tubingen. Greece: Aghia Sophia Children’s Hospital, Thivon and Papadiamantopoulou, Athens. Italy: Fondazione IRCCS Policlinico San Matteo, Pavia; Azienda Ospedaliera-University of Padova, Padova; University of Milano-Bicocca, MBBM Foundation c/o San Gerardo Hospital, Monza; IRCCS Ospedale Pediatrico Bambino Gesù, Roma; Meyer Children Hospital, Firenze; Centro Trapianti di Midollo Osseo PO Microcitemico, Cagliari. Netherlands: Leiden University Medical Center, Leiden. Spain: Hospital de la Santa Creu i de Sant Pau, Barcelona. Sweden: Sahlgrenska University Hospital, Goeteborg; Karolinska University Hospital Children’s Hospital, Stockholm. United Kingdom: Department of Paediatrics, St. Mary’s Hospital, London, United Kingdom; Birmingham Children's Hospital, Birmingham.

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Authors and Affiliations

  1. Eurocord, Hôpital Saint Louis, Université Paris, Paris, France

    Eliane Gluckman, Barbara Cappelli, Graziana M. Scigliuolo, Fernanda Volt, Karina Tozatto-Maio, Vanderson Rocha & Annalisa Ruggeri

  2. Monacord, Centre Scientifique de Monaco, Monaco, Monaco

    Eliane Gluckman, Barbara Cappelli, Graziana M. Scigliuolo, Fernanda Volt, Karina Tozatto-Maio, Vanderson Rocha & Annalisa Ruggeri

  3. Department of Paediatrics, St. Mary’s Hospital, London, UK

    Josu de la Fuente & Farah O’Boyle

  4. Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Brazil

    Karina Tozatto-Maio

  5. Bone Marrow Transplant Unit, Hospital Sirio Libanes, São Paulo, Brazil

    Vanderson Rocha

  6. Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Mina Tommaso & Marco Zecca

  7. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands

    Frans Smiers & Arjan C. Lankester

  8. Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany

    Claudia Bettoni Da Cunha-Riehm

  9. Pediatric Hematology–Oncology Unit, Department of Women’s and Children’s Health, Azienda Ospedaliera-University of Padova, Padova, Italy

    Elisabetta Calore

  10. Pediatric Clinic—Hemato–Oncology Department, University of Milano-Bicocca, MBBM Foundation c/o San Gerardo Hospital, Monza, Italy

    Sonia Bonanomi

  11. Stem Cell Transplant Unit, Aghia SophiaChildren’s Hospital, Thivon and Papadiamantopoulou, Athens, Greece

    Stelios Graphakos & Anna Paisiou

  12. Pediatric Hematology and Oncology, Dr. von Haunersches University Children’s Hospital, Munich, Germany

    Michael H. Albert

  13. Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy

    Annalisa Ruggeri

  14. Cellular Therapy and Immunobiology WP of EBMT, Leiden, The Netherlands

    Annalisa Ruggeri

  15. Department of Pediatric Hematology Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany

    Selim Corbacioglu

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  1. Eliane Gluckman
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on behalf of Paediatric Diseases (PDWP) and Inborn Errors Working Parties (IEWP) of the EBMT

Contributions

EG, BC, GMS, and FV reviewed the literature, analyzed the data, and wrote the manuscript. All authors were involved in collecting patients’ data, contributed to the intellectual content of the paper and approved the final manuscript.

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Correspondence to Eliane Gluckman.

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Gluckman, E., Fuente, J.d.l., Cappelli, B. et al. The role of HLA matching in unrelated donor hematopoietic stem cell transplantation for sickle cell disease in Europe. Bone Marrow Transplant 55, 1946–1954 (2020). https://doi.org/10.1038/s41409-020-0847-z

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