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Published on: September 6, 2017
Outcomes of Germline Testing for Children with Hematologic Malignancies Undergoing Hematopoietic Cell Transplantation
Arti S Pandey1, Roya Mostafavi2, Emily Ashcraft3
1St Jude Children's Research Hospital, Memphis, Tennessee, United States.
Insights
Genetic evaluation is crucial for children with hematologic malignancies (HM) undergoing hematopoietic cell transplantation (HCT). Identifying germline variants guides therapy and donor selection, improving outcomes.
Area of Science:
- Pediatric Oncology
- Cancer Genetics
- Hematopoietic Cell Transplantation
Background:
- Increasing identification of germline pathogenic variants (PV) in cancer predisposition genes (CPG) among children with hematologic malignancies (HM).
- Germline variant information is critical for guiding leukemia therapy, family genetic testing, and selecting related donors for hematopoietic cell transplantation (HCT).
Purpose of the Study:
- To determine the frequency of genetic evaluation in children with HM undergoing HCT.
- To assess the utilization of germline genetic data in clinical practice for HCT.
- To investigate the impact of germline PV on HCT outcomes.
Main Methods:
- Retrospective review of 286 children with HM who underwent HCT between 2017 and 2023.
- Analysis of the timeline for genetic counseling and testing.
- Examination of germline PV prevalence and correlation with HCT outcomes.
Main Results:
- 79% of children received genetic counseling before HCT, 192 underwent testing, and 142 had results prior to HCT.
- 19% of patients harbored a germline CPG PV, with 6% aligning with their HM diagnosis.
- One of five HCTs from a PV-positive relative resulted in donor-derived leukemia; no significant differences in engraftment, relapse, or survival were observed.
Conclusions:
- Prompt genetic referral and testing are warranted for children with HM to identify hereditary predispositions.
- Germline variant information is essential for informed donor selection in HCT.
- Early genetic evaluation can optimize treatment strategies and outcomes for pediatric HM patients.
Abstract:
Recent studies reveal that a growing proportion of children with hematologic malignancies (HM) harbor germline pathogenic or likely pathogenic variants (hereafter "PV") in cancer predisposing genes (CPG). Identifying these children is critical as the information gained guides leukemia therapy, family testing, and selection of related donors for hematopoietic cell transplantation (HCT). Nevertheless, it remains unclear how often children with HM being considered for HCT undergo genetic evaluation, and whether germline data are used to guide clinical practice. To address this gap, we reviewed the records of 286 children who underwent >1 HCT for HM at our institution between Jan 1, 2017, and Dec. 31, 2023. We examined the timeline of genetic evaluation, prevalence of germline PV, and impact of PV on HCT outcomes. Overall, 227 (79%) children met with a genetic counselor prior to their first HCT, 192 underwent testing, and 142 had results returned before the HCT. Thirty-six patients (19%) harbored a germline CPG PV, among whom 12 (6%) had PV aligning with their HM diagnosis. One of five patients who received an HCT from a PV-positive relative developed donor-derived leukemia. We observed no significant differences in time to neutrophil engraftment, cumulative incidence of relapse, or overall survival between patients with and without PV, although the cohort was heterogeneous with respect to the underlying PV. Given the high prevalence of PV in children with HM, prompt referral to genetics is warranted to ensure timely counseling and germline testing to detect a hereditary predisposition and inform donor selection for HCT.
