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

Abstract:

: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 ADAMTS13, CD46, CFH, and CFI. 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.

journal_name

Thromb Haemost

authors

Gavriilaki E,Touloumenidou T,Sakellari I,Batsis I,Mallouri D,Psomopoulos F,Tsagiopoulou M,Koutra M,Yannaki E,Papalexandri A,Taylor P,Nikolousis E,Stamouli M,Holbro A,Baltadakis I,Liga M,Spyridonidis A,Tsirigotis P,Cha

doi

10.1055/s-0040-1702225

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

638-646

issue

4

eissn

0340-6245

issn

2567-689X

journal_volume

120

pub_type

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