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New Insights Into Risk Factors for Transplant-Associated Thrombotic Microangiopathy in Pediatric HSCT

Lookup NU author(s): Dr Zohreh Nademi, Dr Alex Battersby, Dr Terence Flood, Dr Stephen Owens, Professor Andrew Cant, Sinead Greener, Dr Patrick Walsh, Professor David Kavanagh, Dr Srinivas Annavarapu, Professor Roderick Skinner, Professor Andrew Gennery, Dr Mary Slatter

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This is the final published version of an article that has been published in its final definitive form by American Society of Hematology, 2020.

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Abstract

This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation-based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA was threefold higher among patients who received >1 transplant. TA-TMA rates were significantly higher among patients with acute graft-versus-host disease (aGVHD) grades III to IV vs aGVHD grade 0 to II. On multivariate analysis, the presence of active comorbidity, >1 transplant, aGVHD grade III to IV were risk factors for TA-TMA (odds ratio [OR]: 5.1, 5.2, and 26.9; respectively), whereas the use of cyclosporine A/tacrolimus-based GVHD prophylaxis was not a risk factor for TA-TMA (OR: 0.3). Active comorbidity, subsequent transplant, and aGVHD grades III to IV were significant risk factors for TA-TMA. TA-TMA might represent a form of a vascular GVHD, and therefore, continuing control of aGVHD is important to prevent worsening of TA-TMA associated with GVHD.


Publication metadata

Author(s): Elfeky R, Lucchini G, Lum SH, Ottaviano G, Builes N, Nademi Z, Battersby A, Flood T, Owens S, Cant AJ, Young H, Greener S, Walsh P, Kavanagh D, Annavarapu S, Rao K, Amrolia P, Chiesa R, Worth A, Booth C, Skinner R, Doncheva B, Standing J, Gennery AR, Qasim W, Slatter M, Veys P

Publication type: Article

Publication status: Published

Journal: Blood Advances

Year: 2020

Volume: 4

Issue: 11

Pages: 2418-2429

Online publication date: 09/06/2020

Acceptance date: 09/06/2020

Date deposited: 25/11/2020

ISSN (electronic): 2473-9529

Publisher: American Society of Hematology

URL: https://doi.org/10.1182/bloodadvances.2019001315

DOI: 10.1182/bloodadvances.2019001315

PubMed id: 32492158


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