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• W2912203136 abstract "Telomeres are essential for chromosomal stability and markers of biological age. We evaluated the effect of abnormal telomere biology on survival after unrelated donor hematopoietic cell transplant (HCT) for acquired severe aplastic anemia (SAA). Patient pre-transplant blood samples, and clinical and outcome data were available at the Center for International Blood and Marrow Transplant Research. We used qPCR to measure relative telomere length (RTL) and whole exome sequencing to identify patients with pathogenic (P) or likely pathogenic (LP) variants in telomere biology disorder (TBD) related genes. Cox proportional hazard models were used for survival analysis. The study included 490 SAA patients who received HCT between 1990 and 2013 at a median age of 20 years. Eighty patients (16.3%) had pre-HCT RTL <5th percentile-for-age, and 9.5% had a P or LP variant in a TBD-related gene. A higher frequency of TBD-related gene variants was observed in patients with RTL <5th vs. ³5th percentile-for-age (23.8% vs. 6.6% in patients with p<0.0001). Univariate analysis showed higher post-HCT mortality risk in patients with RTL <5th percentile-for-age (p log-rank=0.04), or patients with P/LP TBD variant (p log-rank=0.05) (Figures 1A, B). In multivariable analysis, and compared to patients with RTL ≥50th percentile, RTL <5th percentile-for-age was associated with higher risk of post-HCT mortality (HR=1.9, 95% CI=1.2-2.9, p=0.005); no survival differences were noted in longer RTL categories (p>0.10 for all other categories). A similar high mortality risk was found in patients with P/LP TBD-related variants (HR=2.0, 95% CI=1.28-3.15, p=0.003). A time-dependent effect for post-HCT mortality was only observed in relation to RTL (HR for RTL <5th percentile vs. longer RTL=1.3, p=0.21 for the first 12 months after HCT, and HR=3.8, p<0.0001, thereafter, p-heterogeneity=0.007). The study findings highlight the importance of telomere biology in post-HCT outcomes for patients with SAA. Telomeres are essential for chromosomal stability and markers of biological age. We evaluated the effect of abnormal telomere biology on survival after unrelated donor hematopoietic cell transplant (HCT) for acquired severe aplastic anemia (SAA). Patient pre-transplant blood samples, and clinical and outcome data were available at the Center for International Blood and Marrow Transplant Research. We used qPCR to measure relative telomere length (RTL) and whole exome sequencing to identify patients with pathogenic (P) or likely pathogenic (LP) variants in telomere biology disorder (TBD) related genes. Cox proportional hazard models were used for survival analysis. The study included 490 SAA patients who received HCT between 1990 and 2013 at a median age of 20 years. Eighty patients (16.3%) had pre-HCT RTL <5th percentile-for-age, and 9.5% had a P or LP variant in a TBD-related gene. A higher frequency of TBD-related gene variants was observed in patients with RTL <5th vs. ³5th percentile-for-age (23.8% vs. 6.6% in patients with p<0.0001). Univariate analysis showed higher post-HCT mortality risk in patients with RTL <5th percentile-for-age (p log-rank=0.04), or patients with P/LP TBD variant (p log-rank=0.05) (Figures 1A, B). In multivariable analysis, and compared to patients with RTL ≥50th percentile, RTL <5th percentile-for-age was associated with higher risk of post-HCT mortality (HR=1.9, 95% CI=1.2-2.9, p=0.005); no survival differences were noted in longer RTL categories (p>0.10 for all other categories). A similar high mortality risk was found in patients with P/LP TBD-related variants (HR=2.0, 95% CI=1.28-3.15, p=0.003). A time-dependent effect for post-HCT mortality was only observed in relation to RTL (HR for RTL <5th percentile vs. longer RTL=1.3, p=0.21 for the first 12 months after HCT, and HR=3.8, p<0.0001, thereafter, p-heterogeneity=0.007). The study findings highlight the importance of telomere biology in post-HCT outcomes for patients with SAA. Figures 1A and 1B.Figure 1BView Large Image Figure ViewerDownload Hi-res image Download (PPT)" @default.
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• W2912203136 date "2019-03-01" @default.
• W2912203136 modified "2023-09-30" @default.
• W2912203136 title "Pre-HCT Telomere Abnormalities and Mortality after Unrelated Donor Hematopoietic Cell Transplant for Severe Aplastic Anemia" @default.
• W2912203136 doi "https://doi.org/10.1016/j.bbmt.2018.12.626" @default.
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