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Use of eculizumab in children with allogeneic haematopoietic stem cell transplantation associated thrombotic microangiopathy - a multicentre retrospective PDWP and IEWP EBMT study

Bone Marrow Transplantation volume 58, pages 129–141 (2023)Cite this article

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Abstract

Terminal complement blockade by humanised monoclonal antibody eculizumab has been used to treat transplantation-associated thrombotic microangiopathy (TA-TMA) in recent years. This retrospective international study conducted by the Paediatric Diseases (PDWP) and Inborn Error Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (EBMT) describes outcome and response of 82 paediatric patients from 29 centres who developed TA-TMA and were treated with eculizumab between January 2014 and May 2019. The median time from hematopoietic stem cell transplantation (HSCT) to TA-TMA manifestation was 92 days (range: 7–606) and from TA-TMA diagnosis to the start of eculizumab treatment 6 days (range: 0–135). Most patients received eculizumab weekly (72%, n = 55) with a standard weight (kg)-based dose (78%, n = 64). Six months from beginning of eculizumab therapy, the cumulative incidence of TA-TMA resolution was 36.6% (95% CI: 26.2–47) and the overall survival (OS) was 47.1% (95% CI: 35.9–57.5). All 43 patients with unresolved TA-TMA died. The cause of death was HSCT-related in 41 patients. This study also documents poor outcome of patients without aGvHD and their frequent concomitant viral infections. Considering recent publications, intensified eculizumab dosing and complement monitoring could potentially improve upon outcomes observed in this study.

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Fig. 1: Outcome parameters: TA-TMA resolution and survival.
Fig. 2: TA-TMA resolution and patient outcome diagram with median time to event or follow-up.

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Acknowledgements

We thank William Boreland for the language editing.

Author information

Authors and Affiliations

  1. National Institute of Children’s Diseases and Comenius Univeristy, Bratislava, Slovakia

    Peter Svec & Julia Horakova

  2. NIHR Great Ormond Street Hospital BRC, UCL Institute of Immunity and Transplantation, Royal Free hospital, London, OH, USA

    Reem Elfeky

  3. EBMT Paris study office, Paris, France

    Jacques-Emmanuel Galimard & Arnaud Dalissier

  4. Saint Antoine Hospital, Sorbonne University, Paris, France

    Jacques-Emmanuel Galimard

  5. UCSF Benioff Children’s Hospital, San Francisco, CA, USA

    Christine S. Higham

  6. Texas Transplant Institute, Methodist Children’s Hospital, San Antonio, TX, USA

    Troy C. Quigg

  7. Hospital Infantil La Paz, Madrid, Spain

    David Bueno Sanchez

  8. Great North Children’s Hospital, Newcastle-Upon-Tyne, United Kingdom

    Su Han Lum

  9. IRCSS, Institute G. Gaslini, Genova, Italy

    Maura Faraci

  10. The Royal Children’s Hospital Melbourne, Melbourne, VIC, Australia

    Theresa Cole

  11. St. Anna Children’s Hospital and Children’s Cancer Research Institute (CCRI), Medical University of Vienna, Vienna, Austria

    Herbert Pichler

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

    Maria Isabel Benítez-Carabante

  13. Hospital Infantil Universitario ‘Niño Jesus’, Madrid, Spain

    Marta Gonzalez -Vicent

  14. Schneider Children’s Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Petach- Tikva, Israel

    Asaf Yanir

  15. Paediatric Onco-Haematology, Regina Margherita Children’s Hospital, University of Torino, Turin, Italy

    Franca Fagioli

  16. University Children’s Hospital, Würzburg, Germany

    Matthias Wölfl

  17. University Children’s Hospital Basel, Basel, Switzerland

    Nicolas von der Weid

  18. Bristol Royal Hospital for Children, Bristol, United Kingdom

    Rachel Protheroe

  19. Central Hospital of Southern Pest, Budapest, Hungary

    Gergely Krivan

  20. Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Center for Pediatrics and Adolescent Medicine, Department of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Freiburg, Germany

    Carsten Speckmann

  21. Leeds Children’s Hospital, Leeds, United Kingdom

    Beki James

  22. University children’s hospital Ljubljana, Ljubljana, Slovenia

    Simona Lucija Avcin

  23. Institut d’Hematologie et d’Oncologie Pediatrique, Lyon, France

    Yves Bertrand

  24. Fondazione MBBM, Milano Bicocca University, Monza, Italy

    Marta Verna

  25. University Hospital Motol, Charles University, Prague, Czech Republic

    Petr Riha

  26. Sheffield Children’s Hospital NHS Foundation Trust, Sheffield, United Kingdom

    Katharine Patrick

  27. Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy

    Simone Cesaro

  28. Wroclaw Medical University, Wroclaw, Poland

    Krzysztof Kalwak

  29. Princess Maxima centre for pediatric oncology / Utrecht University Children’s Hospital, Utrecht, Netherlands

    Marc Bierings

  30. Oslo University Hospital, Oslo, Norway

    Jochen Büchner

  31. Sahlgrenska Univ Hospital, Goeteborg, Sweden

    Karin Mellgren

  32. Semmelweis University, Budapest, Hungary

    Zoltán Prohászka

  33. Pediatric immune-hematology and rheumatology unit, Hospital Necker enfants maladies, Assistance-publique hopitaux de Paris, Paris University, Paris, France

    Bénédicte Neven

  34. Willem-Alexander Children’s Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands

    Arjan Lankester

  35. University of Regensburg, Regensburg, Germany

    Selim Corbacioglu

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  1. Peter Svec
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Contributions

Conception and design of the work: PS, RE, J-EG, ZP, AL, SC, Data collection: PS, RE, CSH, AD, TCQ, DBS, SHL, MF, TC, HP, MIB-C, JH, MG-V, AY, FF, MW, NvdW, RP, GK, CS, BJ, SLA, YB, MV, PR, KP, SC, KK, MB, JB, KM, BN, Data analysis and interpretation: J-EG, AD, PS, SC, Drafting the article: PS, RE, J-EG, Critical revision of the article: PS, RE, J-EG, CSH, TCQ, HP, MW, CS, BJ, SC, JB, ZP, BN, AL, SC, Final approval of the version to be published: all authors.

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Correspondence to Peter Svec.

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TCQ, DO, MS presents educational programs for the diagnosis of thrombotic microangiopathy and paroxysmal nocturnal haemoglobinuria on the speaker’s bureau for Alexion Pharmaceuticals. He has no other financial competing interests. DBS provided advisory services for Alexion Pharmaceuticals. The remaining authors declare no competing interests.

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Svec, P., Elfeky, R., Galimard, JE. et al. Use of eculizumab in children with allogeneic haematopoietic stem cell transplantation associated thrombotic microangiopathy - a multicentre retrospective PDWP and IEWP EBMT study. Bone Marrow Transplant 58, 129–141 (2023). https://doi.org/10.1038/s41409-022-01852-x

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