Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy.
Thromb Haemost
; 120(4): 638-646, 2020 Apr.
Article
en En
| MEDLINE
| ID: mdl-32131130
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Complicaciones Posoperatorias
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Trasplante de Células Madre Hematopoyéticas
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Neoplasias Hematológicas
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Regiones no Traducidas
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Microangiopatías Trombóticas
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Genotipo
Tipo de estudio:
Etiology_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Thromb Haemost
Año:
2020
Tipo del documento:
Article
País de afiliación:
Grecia