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Cytogenetic abnormalities predict survival after allogeneic hematopoietic stem cell transplantation for pediatric acute myeloid leukemia: a PDWP/EBMT study

Bone Marrow Transplantation volume 59, pages 451–458 (2024)Cite this article

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Abstract

Poor-risk (PR) cytogenetic/molecular abnormalities generally direct pediatric patients with acute myeloid leukemia (AML) to allogeneic hematopoietic stem cell transplant (HSCT). We assessed the predictive value of cytogenetic risk classification at diagnosis with respect to post-HSCT outcomes in pediatric patients. Patients younger than 18 years at the time of their first allogeneic HSCT for AML in CR1 between 2005 and 2022 who were reported to the European Society for Blood and Marrow Transplantation registry were subgrouped into four categories. Of the 845 pediatric patients included in this study, 36% had an 11q23 abnormality, 24% had monosomy 7/del7q or monosomy 5/del5q, 24% had a complex or monosomal karyotype, and 16% had other PR cytogenetic abnormalities. In a multivariable model, 11q23 (hazard ratio [HR] = 0.66, P = 0.03) and other PR cytogenetic abnormalities (HR = 0.55, P = 0.02) were associated with significantly better overall survival when compared with monosomy 7/del7q or monosomy 5/del5q. Patients with other PR cytogenetic abnormalities had a lower risk of disease relapse after HSCT (HR = 0.49, P = 0.01) and, hence, better leukemia-free survival (HR = 0.55, P = 0.01). Therefore, we conclude that PR cytogenetic abnormalities at diagnosis predict overall survival after HSCT for AML in pediatric patients.

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Fig. 1: Survival curves.

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Deidentified dataset maybe shared upon request to the corresponding author.

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Acknowledgements

We would like to thank Keith A. Laycock, PhD, ELS for scientific editing of the manuscript. We would like to thank our colleagues, advanced practice providers, nurses, data managers and other healthcare professional who participated in patient care. We would also like to thank the parents who entrusted the care of our children to us. This work was supported by funds from the American Lebanese Syrian Associated Charities (ALSAC) (to Akshay Sharma).

Author information

Authors and Affiliations

  1. Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Akshay Sharma & Senthil Velan Bhoopalan

  2. EBMT Statistical Unit, Hôpital Saint-Antoine, Paris, France

    Jacques-Emmanuel Galimard

  3. Anthony Nolan Research Institute, Imperial College Healthcare NHS Trust, London, UK

    Angharad Pryce

  4. EBMT Paris Study Unit, Hôpital Saint-Antoine, Paris, France

    Arnaud Dalissier

  5. Pediatric Hematology and Immunology Department, Hôpital Robert-Debré, GHU APHP Nord Université Paris Cité, Paris, France

    Jean-Hugues Dalle

  6. Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, Italy

    Franco Locatelli

  7. CHU Bordeaux Groupe Hospitalier Pellegrin-Enfants, Bordeaux, France

    Charlotte Jubert

  8. Paediatric Bone Marrow Transplant Service, Bristol Royal Hospital for Children, Bristol, UK

    Oana Mirci-Danicar

  9. Bone Marrow Transplant Unit, St. Sophia Children’s Hospital Oncology Centre, Athens, Greece

    Vassiliki Kitra-Roussou

  10. Unité de coordination interne et externe, Institut d’Hématologie et d’Oncologie Pédiatrique, Lyon, France

    Yves Bertrand

  11. Centro Trapianti Cellule Staminali, Onco-Ematologia Pediatrica, Ospedale Infantile Regina Margherita, Turin, Italy

    Franca Fagioli

  12. Oncopediatrics department, Nantes University Hospital, Nantes, France

    Fanny Rialland

  13. Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University and Hospital, Padua, Italy

    Alessandra Biffi

  14. Blood and Marrow Transplant Unit, Department of Paediatric Haematology, Royal Manchester Children’s Hospital, Manchester, UK

    Robert F. Wynn

  15. Département Hématologie Oncologie Pédiatrique, Hôpital de la Timone, Marseille, France

    Gérard Michel

  16. Dipartimento di Ematologia Pediatrica, Azienda Ospedaliera di Rilievo Nazionale, Naples, Italy

    Francesco Paolo Tambaro

  17. Department of Paediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Ali Al-Ahmari

  18. King Hussein Cancer Center, Amman, Jordan

    Abdelghani Tbakhi

  19. Department of Paediatric Oncology, Royal Marsden Hospital, London, UK

    Caroline L. Furness

  20. Department of Pediatrics, Niño Jesus Children’s Hospital, Madrid, Spain

    Miguel Angel Diaz

  21. Department of Paediatric Haematology and Oncology, University Hospital Motol, Prague, Czech Republic

    Petr Sedlacek

  22. Bone Marrow Transplant Unit, II Children’s Clinic, University Children’s Hospital, Bratislava, Slovakia

    Ivana Bodova

  23. HSCT Unit, Department of Hematology and Oncology, IRCCS Institute G. Gaslini, Genoa, Italy

    Maura Faraci

  24. Department of Bone Marrow Transplantation, Great Ormond Street Hospital NHS Foundation Trust, London, UK

    Kanchan Rao

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

    Katharina Kleinschmidt & Selim Corbacioglu

  26. Hôpital Armand Trousseau, APHP, Sorbonne Université, Paris, France

    Arnaud Petit

  27. The Royal Hospital for Children, Glasgow, UK

    Brenda Gibson

  28. Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Neel S. Bhatt

  29. Clinical Department of Paediatric Bone Marrow Transplantation, Oncology and Haematology, Wrocław Medical University, Wrocław, Poland

    Krzysztof Kalwak

Authors
  1. Akshay Sharma
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  31. Selim Corbacioglu
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Contributions

AS, NSB and SVB conceptualized and designed the study, interpreted the results, wrote the first draft of the manuscript, and made revisions. J-EG and AD provided data management and performed statistical analysis. KK and SC oversaw the study and provided supervision. Several authors were involved in caring for the patients included in this study at their respective centers. All authors critically reviewed the manuscript, provided comments, and approved the final version.

Corresponding author

Correspondence to Akshay Sharma.

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Competing interests

AS has received consultant fees from Spotlight Therapeutics, Medexus Inc., Vertex Pharmaceuticals, Sangamo Therapeutics, and Editas Medicine. He is a medical monitor for an RCI BMT CSIDE clinical trial for which he receives financial compensation. He has also received research funding from CRISPR Therapeutics and honoraria from Vindico Medical Education. AS is the St. Jude Children’s Research Hospital site principal investigator of clinical trials for genome editing of sickle cell disease sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics (NCT03745287), Novartis Pharmaceuticals (NCT04443907), and Beam Therapeutics (NCT05456880). The industry sponsors provide funding for the clinical trial, which includes salary support paid to AS’s institution. AS has no direct financial interest in these therapies.

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Sharma, A., Galimard, JE., Pryce, A. et al. Cytogenetic abnormalities predict survival after allogeneic hematopoietic stem cell transplantation for pediatric acute myeloid leukemia: a PDWP/EBMT study. Bone Marrow Transplant 59, 451–458 (2024). https://doi.org/10.1038/s41409-024-02197-3

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