Clinical and Genetic Risk Prediction of Cognitive Impairment After Blood or Marrow Transplantation for Hematologic Malignancy.
Purpose: Using a candidate gene approach, we tested the hypothesis that individual single nucleotide polymorphisms (SNPs) and gene-level variants are associated with cognitive impairment in patients with hematologic malignancies treated with blood or marrow transplantation (BMT) and that inclusion o...
| Publicado en: | Journal of Clinical Oncology Vol. 38; no. 12; pp. 1312 - 1323 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
American Society of Clinical Oncology
4/20/2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=142740340&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 142740340 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0732183X 20D jtl: Journal of Clinical Oncology issn: 0732183X maglogo: N pubinfo: dt: 4/20/2020 vid: 38 iid: 12 pid: 26892 pub: American Society of Clinical Oncology place: Alexandria, Virginia artinfo: ui: 142740340 142740340 NLM32083992 142740340 10.1200/JCO.19.01085 NLM32083992 142740340 ppf: 1312 ppct: 11 formats: tig: atl: Clinical and Genetic Risk Prediction of Cognitive Impairment After Blood or Marrow Transplantation for Hematologic Malignancy. aug: au: Sharafeldin, Noha Richman, Joshua Bosworth, Alysia Chen, Yanjun Singh, Purnima Patel, Sunita K. Wang, Xuexia Francisco, Liton Forman, Stephen J. Wong, F. Lennie Bhatia, Smita affil: Institute for Cancer Outcomes and Survivorship, School of Medicine, University of Alabama at Birmingham, Birmingham, AL sug: subj: Hematologic Neoplasms Bone Marrow Transplantation Adverse Effects Hematologic Neoplasms Therapy Disease Susceptibility Middle Age Prospective Studies Male Models, Statistical Polymorphism, Genetic California Hematologic Neoplasms Epidemiology Predictive Value of Tests Neuropsychological Tests Female Bone Marrow Transplantation Statistics and Numerical Data Human Validation Studies Comparative Studies Evaluation Research Multicenter Studies Funding Source Middle Aged: 45-64 years Male Female ab: Purpose: Using a candidate gene approach, we tested the hypothesis that individual single nucleotide polymorphisms (SNPs) and gene-level variants are associated with cognitive impairment in patients with hematologic malignancies treated with blood or marrow transplantation (BMT) and that inclusion of these SNPs improves risk prediction beyond that offered by clinical and demographic characteristics.Patients and Methods: In the discovery cohort, BMT recipients underwent a standardized battery of neuropsychological tests pre-BMT and at 6 months, 1 year, 2 years, and 3 years post-BMT. Associations between 68 candidate genes and cognitive impairment were assessed using generalized estimating equation models. Elastic-Net regression was used to build Base (sociodemographic), Clinical, and Combined (Base plus Clinical plus genetic) risk prediction models of post-BMT impairment. An independent nonoverlapping cohort from the BMT Survivor Study with self-report of learning/memory problems (as identified by their health care provider) was used for model replication.Results: The discovery cohort included 277 participants (58.5% males; 68.6% non-Hispanic whites; and 46.6% allogeneic BMT recipients). Adjusting for BMT type, age at BMT, sex, race/ethnicity, and cognitive reserve, SNPs in the blood-brain barrier, telomere homeostasis, and DNA repair genes were significantly associated with cognitive impairment. Compared with the Clinical Model, the Combined Model had higher predictive power in both the discovery cohort (mean area under the receiver operating characteristic curve [AUC], 0.89; 95% CI, 0.85 to 0.93 v 0.77; 95% CI, 0.71 to 0.83; P = 1.24 × 10-9) and the replication cohort (AUC, 0.71; 95% CI, 0.66 to 0.76 v 0.63; 95% CI, 0.57 to 0.68; P = .004).Conclusion: Inclusion of candidate genetic variants enhanced the prediction of risk of post-BMT cognitive impairment beyond that offered by demographic/clinical characteristics and represents a step toward a personalized approach to managing patients at high risk for cognitive impairment after BMT. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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