A study characterizing hematologic malignancies in Li-Fraumeni Syndrome has identified 10 different subtypes, with most occurring de novo, as lymphoid malignancies, and with good responsiveness to standard treatments. The findings were published in JCO Precision Oncology.

“Li-Fraumeni syndrome is characterized by an increased risk of developing cancers at younger ages and multiple primary cancers,” the study authors explained in their report. “Hematologic malignancies account for 4%-10% of cancers in individuals with Li-Fraumeni syndrome, but their phenotypic spectrum and clinical outcomes remain incompletely characterized.”

The researchers conducted a retrospective cohort study to characterize hematologic malignancy frequency, phenotypes, and outcomes in patients with Li-Fraumeni syndrome. They used cancer genetics registries at 2 universities to identify all unrelated families with Li-Fraumeni syndrome seen between 2010 and the present with at least 1 individual with a pathologically confirmed hematologic malignancy. They also conducted a literature review to identify individuals in the published literature with Li-Fraumeni syndrome with a hematologic malignancy. 

Within the cancer genetics registries, the researchers identified 121 families with Li-Fraumeni syndrome; 17 patients from 16 (13%) families were diagnosed with at least 1 hematologic malignancy (19 total). 

From the literature review, they found an additional 83 patients for whom detailed descriptions were included. Thus, the analysis included a total of 99 patients with Li-Fraumeni syndrome and a hematologic malignancy (median age at the time of first hematologic malignancy diagnosis, 39 years; range, 4-66 years; diagnosed in childhood [<18 years of age], 29%; 53% male).

The study characterized a spectrum of hematologic malignancies, including 10 subtypes. The researchers found there was a propensity for lymphoid over myeloid diagnoses, including acute lymphocytic leukemia (n=6), non-Hodgkin lymphoma (n=5), myelodysplastic syndrome (n=3), chronic lymphocytic leukemia (n=2), acute myeloid leukemia (AML; n=1), Langerhans cell histiocytosis (n=1), and chronic myeloid leukemia (n=1). 

The investigators found that most hematologic malignancies (74%) did not occur after cytotoxic therapy, and they often responded to usual treatment regimens. However, they noted that a subset of patients experienced unusual, severe, or late toxicities, such as decitabine-induced acute respiratory distress syndrome, severe cerebellar toxicity with Hyper-CVAD, severe myelosuppression with 6-mercaptopurine, facial and arm

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Hematologic malignancies account for 4%-10% of cancers in individuals with Li-Fraumeni syndrome, but their phenotypic spectrum and clinical outcomes remain incompletely characterized.

numbness and weakness after low-dose cytarabine, and immune-mediated adverse events following hematopoietic stem-cell transplantation.

“These findings support use of standard [hematologic malignancy] treatments in patients with [Li-Fraumeni syndrome] while monitoring for unique toxicities and awareness of and access to genetic testing for [Li-Fraumeni syndrome] in both myeloid and lymphoid [hematologic malignancy] settings and suggest that hypomethylating agents followed by stem-cell transplant may be viable for [Li-Fraumeni syndrome]-associated myelodysplastic syndrome and AML.”

Disclosure: Some study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.