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Long-term outcome after allogeneic hematopoietic stem cell transplantation for Shwachman–Diamond syndrome: a retrospective analysis and a review of the literature by the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (SAAWP-EBMT)

Bone Marrow Transplantation volume 55, pages 1796–1809 (2020)Cite this article

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Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative procedure in patients with Shwachman–Diamond syndrome (SDS) with bone marrow abnormalities. The results of 74 patients with SDS (6 acute myeloid leukemia, 7 myelodysplastic syndrome, and 61 bone marrow failure) treated with HSCT between 1988 and 2016 are reported. The donor source was: 24% sibling, 8% parent, and 68% unrelated donor. The stem cell source was: 70% bone marrow, 19% peripheral blood stem cells, and 11% cord blood. The conditioning regimen was myeloablative in 54% and reduced intensity in 46%. Neutrophil engraftment was achieved in 84% of patients after a median time of 17.5 days. Graft failure occurred in 15% of HSCTs. Grades I–IV acute and chronic GVHD were observed in 55% and 20% of patients, respectively. After a median follow-up of 7.3 years (95% CI 4.8–10.2), 28 patients died for progression/relapse (7) or toxicity (21). The 5-year overall survival and nonrelapse mortality were 63.3% (95% CI 50.8–73.4) and 19.8% (95% CI 10.8–30.8), respectively. In conclusion, this is the largest series so far reported and confirms that HSCT is a suitable option for patients with SDS. Further efforts are needed to lower transplant-related toxicity and reduce graft failure.

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Fig. 1: Cumulative incidence of neutrophil engraftment in the study patients.
Fig. 2: Overall survival of 74 patients with SDS who received stem cell transplant.
Fig. 3: Overall survival according to the indication to hematopoietic stem cell transplant.
Fig. 4: Nonrelapse mortality curve in study patients.

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Acknowledgements

The authors would like to thank Mr Rodney Seddon for reviewing the English style of manuscript.

Author information

Authors and Affiliations

  1. Paediatric Haematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy

    Simone Cesaro, Margherita Mauro & Gloria Tridello

  2. Clinica di Oncoematologia Pediatrica, University of Padova, Padova, Italy

    Marta Pillon

  3. Department of Pediatric Hematology and Oncology, Hannover Medical University, Hannover, Germany

    Martin Sauer

  4. Leiden University Hospital, Leiden, The Netherlands

    Frans Smiers

  5. G. Gaslini Research Institute (IRRCS), Genova, Italy

    Maura Faraci & Carlo Dufour

  6. Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Cristina Diaz de Heredia

  7. Central Manchester NHS Trust, Manchester, UK

    Robert Wynn

  8. University of Heidelberg, Heidelberg, Germany

    Johann Greil

  9. IRRCS Ospedale Pediatrico Bambino Gesù, Sapienza University, Rome, Italy

    Franco Locatelli

  10. Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Paul Veys

  11. University Hospital Leuven, Leuven, Belgium

    Anne Uyttebroeck

  12. Karolinska University Hospital, Stockholm, Sweden

    Per Ljungman

  13. CHU Nantes, Nantes, France

    Patrice Chevalier

  14. Pediatric Oncology Hematology Unit, Department of Mother, Child and Adolescent, University Hospital of Geneva, Geneva, Switzerland

    Marc Ansari

  15. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Isabel Badell

  16. University Children’s Hospital, Zürich, Switzerland

    Tayfun Güngör

  17. Royal Liverpool University Hospital, Liverpool, UK

    Rahuman Salim

  18. Department of Internal Medicine III, University Hospital of Munich-Grosshadern, LMU, Munich, Germany

    Johanna Tischer

  19. Hematology and Bone Marrow Transplant Unit, Department of Medicine, University of Verona, Verona, Italy

    Cristina Tecchio

  20. Nottingham University, Nottingham, UK

    Nigel Russell

  21. Wroclaw Medical University, Wraclow, Poland

    Alicja Chybicka

  22. Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland

    Jan Styczynski

  23. Central Hospital of Southern Pest—National Institute of Hematology and Infectious Diseases, Budapest, Hungary

    Gergely Krivan

  24. Our Lady’s Children’s Hospital, Dublin, Ireland

    Owen Smith

  25. Schneider Children’s Medical Center of Israel, Petach-Tikva, Israel

    Jerry Stein

  26. First State Pavlov Medical University of St, Petersburg, Russia

    Boris Afanasyev

  27. Hopital d’Enfants, Nancy, France

    Cécile Pochon

  28. Azienda Ospedaliera Universitaria Pisa, Pisa, Italy

    Maria Cristina Menconi

  29. EBMT Data Office, Leiden, The Netherlands

    Paul Bosman

  30. Hopital St. Louis, Paris, France

    Regis Peffault de Latour

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  1. Simone Cesaro
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Appendix

Appendix

List of EBMT contributing centers. Center indentifying code (CIC)

CIC 295 Hannover (Christian Kratz, 4), CIC 285 Padova (Marta Pillon, 4), CIC 160 Paris Necker (Benedicte Neven, 4), CIC 301 Marseille (Gerard Michel, 3), CIC 386 Bristol (Stephen Robinson, 3), CIC 424 Montréal (Henrique Bittencourt, 3), CIC 707 Glasgow (Brenda E. Gibson, 3), CIC 234 Brussels (Xavier Poiré, 2),CIC 203 Leiden (Stijn Halkes, 2), CIC 274 Genova (Edoardo Lanino, 2), CIC 207 Paris St. Louis (Regis Peffault de Latour, 2), CIC 422 Barcelona Vall d’Hebron (Cristina Diaz de Heredia, 2), CIC 521 Manchester (Robert Wynn, 2), CIC 796 Rome (Franco Locatelli, 2), CIC 524 Heidelberg (Johann Greil, 2), CIC 243 London (Paul Veys, 2), CIC 775 Paris Saint Antoine (Mohammad Mohty, 1), CIC 246 Rotterdam (Jan Cornelissen, 1), CIC 457 Istanbul (Gülyüz Öztürk, 1), CIC 535 Tübingen (Rupert Handgretinger,1), CIC 539 London (Mickey Koh, 1), CIC 631 Paris Robert Debre (Jean-Hughes Dalle, 1), CIC 751 Athens (Vassiliki Kitra-Rossou, 1), CIC 806 Lyon (Yves Bertrand, 1). CIC 209 Leuven (Anne Uyttebroek,1), CIC 212 Stockholm (Per Ljungman,1), CIC 253 Nantes (Patrice Chevalier, 1), CIC 261 Geneva (Marc Ansari, 1), CIC 260 Barcelona Santa Creu i Sant Pau (Isabel Badell, 1), CIC 208 Zürich (Tayfun Güngör, 1), CIC 501 Liverpool (Salim Rahuman, 1), CIC 513 Munich (Johanna Tischer, 1), CIC 623 Verona (Cristina Tecchio, 1), CIC 717 Nottingham (Nigel Russel, 1), CIC 817 Wroclaw (Alicia Chybicka, 1), CIC 764, Bydgoszcz, (Jan Styczynski, 1), CIC 824 Budapest (Krisztian Kallay, 1), CIC 774 Dublin (Owen Smith, 1), CIC 775 Petach-Tikva (Jerry Stein, 1), CIC 725 St. Petersburg (Boris Afanasyev,1), CIC 676 Nancy (Cécile Pochon, 1), CIC 795 Pisa (Maria Cristina Menconi, 1).

Collaborators

CIC 160 Paris Necker (Benedicte Neven, 4), CIC 301 Marseille (Gerard Michel, 3), CIC 386 Bristol (Stephen Robinson, 3), CIC 424 Montréal (Henrique Bittencourt, 3), CIC 707 Glasgow (Brenda E. Gibson, 3), CIC 234 Brussels (Xavier Poiré, 2), CIC 775 Paris Saint Antoine (Mohammad Mohty, 1), CIC 246 Rotterdam (Jan Cornelissen, 1), CIC 457 Istanbul (Gülyüz Öztürk, 1), CIC 535 Tübingen (Rupert Handgretinger,1), CIC 539 London (Mickey Koh, 1), CIC 631 Paris Robert Debre (Jean-Hughes Dalle, 1), CIC 751 Athens (Vassiliki Kitra-Rossou, 1), CIC 806 Lyon (Yves Bertrand, 1).

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Cesaro, S., Pillon, M., Sauer, M. et al. Long-term outcome after allogeneic hematopoietic stem cell transplantation for Shwachman–Diamond syndrome: a retrospective analysis and a review of the literature by the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (SAAWP-EBMT). Bone Marrow Transplant 55, 1796–1809 (2020). https://doi.org/10.1038/s41409-020-0863-z

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