Abstract
Abstract
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.