JCO Precis Oncol. 2025 Jun;9:e2400860. doi: 10.1200/PO-24-00860. Epub 2025 Jun 20.
ABSTRACT
PURPOSE: Hematologic malignancies (HMs) account for 4%-10% of cancers in individuals with Li-Fraumeni syndrome (LFS), but their phenotypic spectrum and clinical outcomes remain incompletely characterized.
METHODS: We conducted a retrospective cohort study at The University of Utah and University of Wisconsin-Madison. Cancer genetics registries were reviewed to identify all unrelated families with LFS seen between 2010 and the present with at least one individual with a pathologically confirmed HM. A literature review was conducted to identify individuals in the published literature with LFS with an HM. HM molecular characteristics, treatment, and outcomes were recorded.
RESULTS: Among 121 total families with LFS at our institutions, 17 patients from 16 (13%) families diagnosed with LFS had an HM. A literature review found an additional 83 patients with detailed descriptions, for a total of 99 patients with LFS and an HM. The spectrum of HMs included 10 subtypes with a propensity for lymphoid over myeloid diagnoses. Most HMs did not occur after cytotoxic therapy and often responded to usual sporadic HM regimens, but in a subset, unusual toxicities were encountered, especially after hematopoietic stem-cell transplantation.
CONCLUSION: Our large cohort of patients with HM and LFS suggest a broad spectrum of HMs in LFS with more lymphoid than myeloid, more de novo than postcytotoxic therapy, and more favorable outcomes than previous reports.
PMID:40540701 | DOI:10.1200/PO-24-00860
