Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy.

Gavriilaki, Eleni, Touloumenidou, Tasoula, Sakellari, Ioanna, Batsis, Ioannis, Mallouri, Despina, Psomopoulos, Fotis, Tsagiopoulou, Maria, Koutra, Maria, Yannaki, Evangelia, Papalexandri, Apostolia, Taylor, Pat, Nikolousis, Emmanuel, Stamouli, Maria, Holbro, Andreas, Baltadakis, Ioannis, Liga, Maria, Spyridonidis, Alexandros, Tsirigotis, Panagiotis, Charchalakis, Nikolaos, Tsakiris, Dimitrios A, Brodsky, Robert A, Passweg, Jacob, Stamatopoulos, Kostas and Anagnostopoulos, Achilles (2020) Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy. Thrombosis and haemostasis. ISSN 2567-689X.

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Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pretransplant genetic susceptibility is evident in adult TA-TMA and further investigated the association of TMA-associated variants with clinical outcomes. We studied 40 patients with TA-TMA, donors of 18 patients and 40 control non-TMA HCT recipients, without significant differences in transplant characteristics. Genomic DNA from pretransplant peripheral blood was sequenced for TMA-associated genes. Donors presented significantly lower frequency of rare variants and variants in exonic/splicing/untranslated region (UTR) regions, compared with TA-TMA patients. Controls also showed a significantly lower frequency of rare variants in , , , and The majority of TA-TMA patients (31/40) presented with pathogenic or likely pathogenic variants. Patients refractory to conventional treatment (62%) and patients that succumbed to transplant-related mortality (65%) were significantly enriched for variants in exonic/splicing/UTR regions. In conclusion, increased incidence of pathogenic, rare and variants in exonic/splicing/UTR regions of TA-TMA patients suggests genetic susceptibility not evident in controls or donors. Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pretransplant genomic screening may be useful to intensify monitoring and early intervention in patients at high risk for TA-TMA.

Item Type: Article
Subjects: WH Haemic and lymphatic systems. Haematology
Divisions: Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Mrs Yolande Brookes
Date Deposited: 06 Mar 2020 12:57
Last Modified: 06 Mar 2020 12:57

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