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Myelodysplastic syndrome

Male sex and the pattern of recurrent myeloid mutations are strong independent predictors of blood transfusion intensity in patients with myelodysplastic syndromes

Leukemia volume 33, pages 522–527 (2019)Cite this article

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Patients with myelodysplastic syndromes (MDS) frequently receive large numbers of blood transfusions due to inefficient hematopoiesis [1, 2], with 94 and 48% of MDS patients receiving more than one red cell and platelet unit respectively during the course of their disease [3, 4]. Transfusion dependency in MDS is associated with reduced survival and significant impairment in quality of life [1, 4, 5]. Despite the extensive use of blood products in MDS, little is known about the clinical and disease-specific factors that drive red cell and platelet transfusion need in these patients. In this study, we added mutational patterns to clinical data and transfusion information in a large cohort of MDS patients to investigate predictors of transfusion intensity and the association between transfusion patterns and survival.

A retrospective cohort of 309 consecutive patients from the MDS biobank at the Karolinska University Hospital, Stockholm, Sweden, diagnosed between 2003 and 2013, met the inclusion criteria of MDS or MDS/myeloproliferative neoplasm according to the revised World Health Organization (WHO) 2008 classification (Supplementary Figure 1). Clinical and laboratory data for each patient, including mutational status at diagnosis, was linked to their transfusion history, comprehensively retrieved from the local transfusion database (Supplementary Table 1). Patients were followed with regard to transfusion history from the date of diagnosis until the date of death, allogeneic stem cell transplantation (SCT), or 1 December 2013, whichever occurred first. The mutations were categorized according to their involvement in histone modulation, DNA methylation, DNA splicing, cohesin complex, and signaling or transcriptional regulation, in analogy with previously published data [6,7,8]. TP53 mutations were considered separately, and ‘other mutations’, occurring in only a few patients each, were grouped together (Supplementary Table 2). All patients were treated according to the Nordic guidelines (www.nmds.org) which follow the European Recommendations for treatment of MDS [9] (Supplementary Table 3). The study was approved by the Regional Ethical Committee in Stockholm.

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References

  1. Cazzola M, Malcovati L. Myelodysplastic syndromes--coping with ineffective hematopoiesis. N Eng J Med. 2005;352:536–8.

    Article  CAS  Google Scholar 

  2. Zhao J, Ryden J, Wikman A, Norda R, Stanworth SJ, Hjalgrim H. et al. Blood use in hematologic malignancies: a nationwide overview in Sweden between 2000 and 2010. Transfusion. 2018;58:390–401.

    Article  Google Scholar 

  3. Ramsey SD, McCune JS, Blough DK, McDermott CL, Beck SJ, Lopez JA, et al. Patterns of blood product use among patients with myelodysplastic syndrome. Vox Sang. 2012;102:331–7.

    Article  CAS  Google Scholar 

  4. Platzbecker U, Hofbauer LC, Ehninger G, Holig K. The clinical, quality of life, and economic consequences of chronic anemia and transfusion support in patients with myelodysplastic syndromes. Leuk Res. 2012;36:525–36.

    Article  Google Scholar 

  5. de Swart L, Smith A, Johnston TW, Haase D, Droste J, Fenaux P, et al. Validation of the revised international prognostic scoring system (IPSS-R) in patients with lower-risk myelodysplastic syndromes: a report from the prospective European LeukaemiaNet MDS (EUMDS) registry. Br J Haematol. 2015;170:372–83.

    Article  Google Scholar 

  6. Tobiasson M, McLornan DP, Karimi M, Dimitriou M, Jansson M, Ben Azenkoud A, et al. Mutations in histone modulators are associated with prolonged survival during azacitidine therapy. Oncotarget. 2016;7:22103–15.

    Article  Google Scholar 

  7. Karimi M, Nilsson C, Dimitriou M, Jansson M, Matsson H, Unneberg P, et al. High-throughput mutational screening adds clinically important information in myelodysplastic syndromes and secondary or therapy-related acute myeloid leukemia. Haematologica. 2015;100:e223–5.

    Article  Google Scholar 

  8. Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122:3616–27. quiz 99

    Article  CAS  Google Scholar 

  9. Malcovati L, Hellstrom-Lindberg E, Bowen D, Ades L, Cermak J, Del Canizo C, et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122:2943–64.

    Article  CAS  Google Scholar 

  10. Malcovati L, Papaemmanuil E, Ambaglio I, Elena C, Galli A, Della Porta MG, et al. Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. Blood. 2014;124:1513–21.

    Article  CAS  Google Scholar 

  11. Jadersten M, Malcovati L, Dybedal I, Della Porta MG, Invernizzi R, Montgomery SM, et al. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol. 2008;26:3607–13.

    Article  Google Scholar 

  12. Garelius HK, Johnston WT, Smith AG, Park S, de Swart L, Fenaux P. et al. Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome. J Intern Med. 2017;281:284–99.

    Article  CAS  Google Scholar 

  13. Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Eng J Med. 2016;375:2023–36.

    Article  CAS  Google Scholar 

  14. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–32.

    Article  CAS  Google Scholar 

  15. Malcovati L, Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005;23:7594–603.

    Article  Google Scholar 

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Acknowledgements

This study was supported by independent grants to PH and EH-L from the Swedish Research Council, the Swedish Cancer Society, Radiumhemmets Forskningsfonder and the Stockholm City Council. JR was supported by a research residence grant from the Stockholm City Council. We thank all members of the PH, EH-L, and GE groups for discussions.

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Authors and Affiliations

  1. Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden

    Jenny Rydén, Mohsen Karimi, Gunilla Walldin, Magnus Tobiasson, Eva Hellström-Lindberg & Petter Höglund

  2. Hematology Center, Karolinska University Hospital, Stockholm, Sweden

    Jenny Rydén, Magnus Tobiasson & Eva Hellström-Lindberg

  3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Gustaf Edgren

  4. Department of Cardiology, Södersjukhuset, Stockholm, Sweden

    Gustaf Edgren

  5. Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden

    Agneta Wikman & Petter Höglund

  6. Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden

    Agneta Wikman

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  1. Jenny Rydén
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Correspondence to Petter Höglund.

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Rydén, J., Edgren, G., Karimi, M. et al. Male sex and the pattern of recurrent myeloid mutations are strong independent predictors of blood transfusion intensity in patients with myelodysplastic syndromes. Leukemia 33, 522–527 (2019). https://doi.org/10.1038/s41375-018-0256-0

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