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Stem cell transplantation

European experience and risk factor analysis of donor cell-derived leukaemias/MDS following haematopoietic cell transplantation

Abstract

Donor cell leukaemia (DCL) is a rare complication of allogeneic haematopoietic cell transplantation (HCT). We have investigated the prevalence and outcome of donor cell haematology malignancies within centres registered with the European Society of Blood and Marrow transplantation (EBMT). We have sought to identify risk factors to shed light on the pathogenesis of DCL as a model for leukaemogenesis. DCL cases were identified by questionnaire and a follow-up questionnaire requested detailed data. Control subjects from the EBMT registry who had not developed DCL were used for a matched pair analysis to identify risk factors. We identified 38 patients with DCL; the estimated prevalence was 80.5/100,000 transplants. Patients were predominantly treated for haematological malignancy. A clone was retrospectively identified in 7/25 (28%) donors for whom data was available. Overall survival was poor with 29/38 patients dead a median of 11 (range 0–91) months after DCL diagnosis. Matched case-pair analysis identified three factors on multivariate analysis as significantly associated with an increased risk for DCL: use of growth factors within the first 100 days after transplantation, in vivo T-cell depletion and multiple allografts. The risk factors identified, support reduced immune surveillance and replicative stress as pathogenic in the development of DCL.

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Acknowledgements

The following individuals and centres are acknowledged for contributing patient data to this work: Gerard Michel, Marseille; Regis Peffault de la Tour, Paris; Marc Bierings, Utrecht; Norbert Ifrah, Angers; Paul Browne, Dublin; Mats Brune, Goeteorg Gothenburg; Arnold Ganser, Hannover; Keith Wilson, Cardiff; Selmin Ataergin, Ankara; Christian Peschel, Munich; Axel Fauer, Idar-Oberstein; RikSchots, Brussels; Nigel Russel, Nottingham, Silvia Montoto, London; John Snowden, Sheffield; John Murray, Manchester; Gerhard Held; Homburg; Jose Diez-Martin, Madrid.

Author contributions

Prof. Kolb and Prof. Tichelli initiated the study. Prof. Kolb, Prof. Tichelli, Prof. Socie, Dr. Rovo, Dr. Salooja, Dr. Engel, Dr. Badoglio and Dr. Labopin were involved in the study design. Dr. Engel, Dr. Badoglio, Dr. Rovo, Dr. Labopin and Dr. Basak were involved in the data collection. Dr. Salooja, Dr. Engel, Dr. Badoglio, Dr. Labopin, Dr. Rovo were involved in the data analysis. All authors were involved in data interpretation and all authors were involved in the writing of the manuscript.

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Correspondence to Nina Salooja.

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Engel, N., Rovo, A., Badoglio, M. et al. European experience and risk factor analysis of donor cell-derived leukaemias/MDS following haematopoietic cell transplantation. Leukemia 33, 508–517 (2019). https://doi.org/10.1038/s41375-018-0218-6

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