Hematologic Malignancy Frequency, Phenotypes, and Outcomes in Li-Fraumeni Syndrome.

Abstract

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. 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. 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. 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.