Retrospective analysis of outcomes of adult patients with L-Fraumeni syndrome and myeloid neoplasms

Li-Fraumeni syndrome (LFS) is an inherited cancer predisposition syndrome. Hematologic malignancies are not considered LFS defining tumors; however, both acute lymphoblastic leukemia (ALL) and therapy-related myeloid neoplasms (MNs) in LFS are described. A retrospective analysis of LFS patients at MD Anderson Cancer Center (Houston, TX) investigated treatment approaches and outcomes of patients who developed an MN. 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 patients (79%) were female. Eight patients (57%) 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%) MDS and one (17%) AML patients achieved an overall response; considering all lines of therapy received, cumulatively six (75%) MDS patients and five (83%) AML/MPAL patients achieved an overall response. At 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. The authors conclude that long-term survival in most patients with LFS developing MN are poor.