| 11. |
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| 12. |
- Kim, KH, et al.
(author)
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Clonal hematopoiesis in the donor does not adversely affect long-term outcomes following allogeneic hematopoietic stem cell transplantation: result from a 13-year follow-up
- 2023
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 108:7, s. 1817-1826
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Journal article (peer-reviewed)abstract
- Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HCT), but the potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HCT and the corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 34 genes covering mutations involved in clonal hematopoiesis with indeterminate potential (CHIP) and other AML-related mutations. A total of 30 mutations were detected from 25 donors (6.7%): the most frequently mutated gene was TET2 (n=7, 28%), followed by DNMT3A (n=4, 16%), SMC3 (n=3, 12%) and SF3B1 (n=3, 12%). With a median follow-up duration of 13 years among survivors, the presence of CHIP in the donor was not associated with recipient overall survival (p=0.969), relapse incidence (p=0.600) or non-relapse mortality (p=0.570). Donor CHIP did not impair neutrophil (p=0.460) or platelet (p=0.250) engraftment, the rates of acute (p=0.490), or chronic graft-vs-host disease (p=0.220). No significant difference was noted for secondary malignancy following HCT between the two groups. The present study suggests that the presence of CHIP in allogeneic stem donors does not adversely affect transplant outcomes after HCT. Accordingly, further study is warranted to reach a clearer conclusion on whether molecular profiling to determine the presence of CHIP mutations is necessary for the pre-transplant evaluation of donors prior to stem cell donation.
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| 13. |
- Kim, KH, et al.
(author)
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Clonal hematopoiesis in the donor does not adversely affect long-term outcomes following allogeneic hematopoietic stem cell transplantation: result from a 13-year follow-up
- 2023
-
In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 108:7, s. 1817-1826
-
Journal article (peer-reviewed)abstract
- Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HCT), but the potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HCT and the corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 34 genes covering mutations involved in clonal hematopoiesis with indeterminate potential (CHIP) and other AML-related mutations. A total of 30 mutations were detected from 25 donors (6.7%): the most frequently mutated gene was TET2 (n=7, 28%), followed by DNMT3A (n=4, 16%), SMC3 (n=3, 12%) and SF3B1 (n=3, 12%). With a median follow-up duration of 13 years among survivors, the presence of CHIP in the donor was not associated with recipient overall survival (p=0.969), relapse incidence (p=0.600) or non-relapse mortality (p=0.570). Donor CHIP did not impair neutrophil (p=0.460) or platelet (p=0.250) engraftment, the rates of acute (p=0.490), or chronic graft-vs-host disease (p=0.220). No significant difference was noted for secondary malignancy following HCT between the two groups. The present study suggests that the presence of CHIP in allogeneic stem donors does not adversely affect transplant outcomes after HCT. Accordingly, further study is warranted to reach a clearer conclusion on whether molecular profiling to determine the presence of CHIP mutations is necessary for the pre-transplant evaluation of donors prior to stem cell donation.
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| 20. |
- Van Asbroeck, Stephanie, et al.
(author)
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Lifestyle and incident dementia: A COSMIC individual participant data meta-analysis
- 2024
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In: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279. ; 20:6, s. 3972-3986
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Journal article (peer-reviewed)abstract
- INTRODUCTIONThe LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODSWe combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTSA one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged <= 75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSIONModifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. Highlights A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.
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