|The following article features coverage from the 2021 Annual Meeting of the Society of Hematologic Oncology (SOHO). Click here to read more of Hematology Advisor‘s conference coverage.|
According to the results of a study presented at the Annual Meeting of the Society of Hematologic Oncology (SOHO), researchers were able to identify a higher percentage of patients with germline predisposition syndromes (GPS) without syndromic features using an algorithmic approach compared with classic methods.
“Germline predisposition syndromes or GPS result from germline mutations in critical tumor suppressor or homeostatic genes, which confer an increased risk for all kinds of cancers and malignancies, but there is a growing list of genes which are associated with hematological neoplasms specifically,” explained Alejandro Ferrer, PhD, of Mayo Clinic, Rochester, MN, which has established a GPS/Inherited Bone Marrow Failure Clinic.
With their study, the investigators sought to demonstrate the heterogeneity of GPS and the benefits of an algorithmic approach to identify non-syndromic GPS patients. To do so, they retrospectively reviewed medical records of patients diagnosed with GPS at the clinic between 1994 and 2018. Then, they prospectively evaluated new pediatric and adult patients with GPS diagnosed between 2017 and 2020 using an algorithmic approach.
The approach included an evaluation of relevant family history, phenotype-specific functional assays such as telomere measurement, germline genetic testing using a custom-designed gene panel, and whole-exome sequencing for negative cases. The total number of patients diagnosed with GPS, retrospectively and prospectively, were compared.
The study included 144 patients who presented with hematologic malignancy with antecedent thrombocytopenia (19.4%), without antecedent thrombocytopenia (18.8%), with inherited bone marrow failure (50%), and with general cancer predisposition syndrome (11.8%). The retrospectively evaluated group had 85 patients, and the prospectively evaluated group had 59 patients. Among retrospective group, 7.1% of patients (n=6) did not present syndromic features; whereas among the prospective group that was evaluated using the algorithmic approach, 14.7% of patients (n=9) were non-syndromic.
Among patients who were prospectively evaluated, the investigators reported that the detection of GPS positively impacted medical care in 91% of cases, including proper selection of a bone marrow donor, selection of drug and conditioning regimens, and genetic counseling.
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Ferrer A, Martin E, Mangaonkar A, et al. AML-345: Algorithmic diagnostic approach and spectrum of hematological malignancies in patients with germline predisposition syndromes. Paper presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 8-11, 2021. Abstract AML-345