Outcomes of adult patients with Li‐Fraumeni syndrome and myeloid neoplasms

BACKGROUND: Li-Fraumeni syndrome (LFS) is an inherited cancer predisposition syndrome. Hematologic malignancies are not considered LFS defining tumors, however, both acute lymphoblastic leukemia and therapy-related myeloid neoplasms (MNs) in LFS are described. Treatment approaches and outcomes of MN in LFS need further evaluation. METHODS: The authors performed a retrospective analysis to understand treatment approaches and outcomes in patients with LFS who developed an MN. RESULTS: Among 190 patients with LFS between February 2001 and February 2026 with a history of at least one neoplasm, 14 (7%) had an MN. Median age at MN diagnosis was 43 years (range, 25-73) and 11 (79%) patients were female. Overall, eight (57%) patients had myelodysplastic syndrome (MDS), five (36%) had acute myeloid leukemia (AML), and one (7%) had T-myeloid mixed phenotype acute leukemia (MPAL). With frontline therapy, six (75%) patients with MDS and one (17%) patient with AML achieved an overall response. Considering all lines of therapy received, cumulatively six (75%) patients with MDS and five (83%) patients with AML/MPAL achieved an overall response. At a median follow-up of 28.8 months, the median overall survival (OS) was 18.2 months, and 1-year and 2-year OS rates were 77% and 17%, respectively. Five patients (two MDS, two AML, and one MPAL) underwent hematopoietic stem cell transplantation during their MN therapy with a median OS of 19.3 months. CONCLUSION: Although short-lived responses to leukemia-directed therapy are common, long-term survival in most patients with LFS developing MN are poor. Additional research and understanding of the mechanisms to prevent MN and to improve MN treatment in LFS are needed.