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High mortality in hematopoietic stem cell transplant-associated thrombotic microangiopathy with and without concomitant acute graft-versus-host disease

Bone Marrow Transplantation volume 54, pages 540–548 (2019)Cite this article

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Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) remains a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We hypothesized that TA-TMA correlates with steroid-refractory acute graft-vs.-host disease (aGvHD) and assessed 660 patients suffering from either AML n = 248, ALL n = 79, CML n = 23, CLL n = 36, lymphoma/myeloma n = 127, MDS/MPN n = 124 or bone marrow failure n = 22, who met the study inclusion criteria and had undergone myeloablative (78%) and non-myeloablative (22%) allo-HSCT between 2006 and 2016. Sixty-five (9.8%) of these patients matched the established diagnostic criteria for TA-TMA, and TA-TMA was shown to be a relevant independent risk factor for mortality (RR 3.27; 95% CI 2.07–5.16). Patients with TA-TMA and concomitant aGvHD had a markedly reduced OS compared to patients with TA-TMA or aGvHD alone (median 5.6 months vs. 7.6 months vs. 55.4 months, respectively; p < 0.0001). Risk factors for development of TA-TMA were aGvHD ≥ grade 2, higher aGvHD grade, steroid-refractory aGvHD, CMV reactivation/end-organ disease, but not the conditioning regimen (RIC or MAC), usage of TBI or TBI dose, underlying disease, donor type, age or sex. TA-TMA, with or without concomitant aGvHD, is a significant complication after allo-HSCT and a high-risk factor for a poor survival outcome. Thus, allo-HSCT recipients with grade 2–4 aGvHD or CMV viremia should be closely monitored for the presence of TA-TMA.

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Acknowledgements

The study was supported by a grant from the Krebsliga beider Basel (grant no. KLbB-4176-03-2017) to MM.

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  1. These authors contributed equally: Sarah Kraft, Noémie Bollinger, Benjamin Bodenmann.

  2. These senior authors contributed equally: Alexandar Tzankov, Michael Medinger.

Authors and Affiliations

  1. Divisions of Hematology, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    Sarah Kraft, Noémie Bollinger, Benjamin Bodenmann, Dominik Heim, Christoph Bucher, Claudia Lengerke, Martina Kleber, Dimitrios A. Tsakiris, Jakob Passweg & Michael Medinger

  2. Divisions of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    Martina Kleber & Michael Medinger

  3. Institute of Medical Genetics and Pathology, University Hospital Basel, Schoenbeinstrasse 40, 4031, Basel, Switzerland

    Alexandar Tzankov

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Kraft, S., Bollinger, N., Bodenmann, B. et al. High mortality in hematopoietic stem cell transplant-associated thrombotic microangiopathy with and without concomitant acute graft-versus-host disease. Bone Marrow Transplant 54, 540–548 (2019). https://doi.org/10.1038/s41409-018-0293-3

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