Clinical implementation of genetic testing in adults for hereditary hematologic malignancy syndromes

As research on hereditary hematologic malignancy syndromes (HHMS) are accumulating, cancer genetics clinics are identifying more adult hematology patients with an inherited component to their disease. However, investigations for HHMS are complex, and there is no formal consensus on genetic testing criteria.

We developed genetic testing criteria for adult hematology patients through a comprehensive literature review and our experience at the Princess Margaret Cancer Centre. We validated our criteria by applying them retrospectively to patients referred to our clinic for HHMS assessment.

Our genetic testing criteria are comprehensive of myeloid malignancies, lymphoid malignancies, and bone marrow failure, including age at diagnosis, family history, and genetic test results in blood and bone marrow. Of the 104 patients who met the criteria, 26% had at least 1 actionable variant in any gene associated with an increased risk of cancer and 13% had an actionable variant resulting in an HHMS diagnosis. A total of 15 patients had incidental findings, including 11 patients with a pathogenic variant associated with carrier status for an autosomal recessive disorder and 4 patients with a mosaic result.

Our high gene positivity rate shows the utility of a broad approach to germline testing in an adult hematology population.