Outcomes of Germline Testing for Children with Hematologic Malignancies Undergoing Hematopoietic Cell Transplantation.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source 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.