Dataset Information

Clinical and Genetic Risk Prediction of Cognitive Impairment After Blood or Marrow Transplantation for Hematologic Malignancy.

ABSTRACT:

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.

SUBMITTER: Sharafeldin N

PROVIDER: S-EPMC8265387 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Recent studies have shown that haploidentical hematopoietic stem cell transplantation supported by third-party cord blood (haplo-cord-HSCT) results in rapid hematopoietic recovery, low incidences of graft-versus-host disease (GVHD), and relapse of hematologic malignancies. However, few reports on haploidentical peripheral blood stem cell transplantation supported by third-party cord blood (haplo-cord-PBSCT) have been published. To evaluate the outcomes of patients who underwent haplo-cord-PBSCT or human leukocyte antigen (HLA)-matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT), we retrospectively reviewed the clinical data of patients with hematologic malignancies who underwent haplo-cord-PBSCT (n = 93) or MSD-PBSCT (n = 72) in our hospital from March 2017 to December 2020. In the haplo-cord-PBSCT and MSD-PBSCT groups, the median time for neutrophil and platelet engraftment was 13 vs. 12 days (p = 0.07) and 16 vs. 13 days (p = 0.06), respectively. The 30-day cumulative incidences of neutrophil engraftment were 100.0% and 98.6% (p = 0.12). The 100-day cumulative incidences of platelet engraftment were 96.8% and 98.6% (p = 0.01). The 100-day cumulative incidences of grade II–IV and grade III–IV acute GVHD were 29.1% vs. 23.6% (p = 0.42) and 9.7% vs. 4.2% (p = 0.18). The cumulative incidences of total and moderate/severe chronic GVHD at 1 year were 26.5% vs. 17.4% and 8.1% vs. 4.5%, respectively, and at 3 years were 34.7% vs. 34.3% (p = 0.60) and 13.6% vs. 10.6% (p = 0.49), respectively. The cumulative incidences of relapse at 1 year were 9.3% and 7.2% and at 3 years were 17.0% and 17.0% (p = 0.98). Non-relapse mortality (NRM) at 1 year was 14.6% and 8.6% and at 3 years was 17.4% and 8.6% (p = 0.13) in two groups. The probabilities of overall survival (OS), disease-free survival (DFS), and GVHD-free/relapse-free survival (GRFS) at 1 year were 81.7% vs. 88.6%, 76.1% vs. 84.2%, and 71.7% vs. 79.7%, respectively, and at 3 years were 78.7% vs. 79.0%, 65.6% vs. 74.4%, and 55.5% vs. 63.6%, respectively, in the corresponding group, p > 0.05. In conclusion, for patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) and acute lymphoid leukemia (ALL), haplo-cord-PBSCT results in similar outcomes compared with MSD-PBSCT, and it may be a valid alternative transplantation method.