Rethinking Genetic Testing Guidelines: Study Reveals Significant Prevalence of Cancer Predisposition Syndromes in Pediatric Leukemia Patients
June 14, 2023
Pediatric cancer and genetics researchers from UPMC Children’s Hospital of Pittsburgh and the University of Pittsburgh published results of a new study exploring the prevalence of cancer predisposition syndromes (CPS) in pediatric leukemia patients and its correlation with their medical history. The study was published online first in March 2023 in the Journal of Pediatric Hematology Oncology.
Julia Meade, MD, assistant professor of Pediatrics and Human Genetics was the senior author of the study. Dr. Meade directs the Pediatric Cancer Predisposition Program in the Division of Pediatric Hematology/Oncology at UPMC Children’s.
Dr. Meade’s study collaborators include Kristen R. D’Aquila, MSGC (lead author), and Andrea Durst, PhD, both from the Department of Human Genetics at the University of Pittsburgh Graduate School of Public Health; Kristine L. Cooper, MS, from the UPMC Hillman Cancer Center Biostatistics Facility; and Elena Kessler, MSGC, formerly of the Division of Medical Genetics in the Department of Pediatrics.
This study builds upon prior work by Dr. Meade and colleagues investigating cancer predisposition syndromes in pediatric patients, including work on referral patterns and barriers to referrals for patients which you can read about in this article from October, 2022.
Study Aims, Design, and Key Clinical Findings/Practice Implications
Dr. Meade and colleagues study focused on cancer predisposition syndromes (CPS) among children diagnosed with leukemia and myelodysplastic syndrome (MDS). CPS are genetic conditions that raise the risk of cancer. Although it's estimated that 5-10% of children with cancer have a CPS, the referral guidelines for screening for leukemia-related CPS are ambiguous and largely dependent on expert opinion.
Because of a lack of cohesive guidelines for referral and testing in this patient population, Dr. Meade’s team sought to clarify the prevalence of CPS in children who underwent genetic testing and to identify any correlations between the patients' medical history and the diagnosis of an underlying CPS.
The study covered patient data from a four-year span beginning in November 2017 through November 2021. 124 children diagnosed with leukemia or MDS were identified through patient records and included in the study cohort. The average age of the patients at the time of their leukemia diagnosis was approximately 6.6 years. The study consisted mostly of children diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and MDS though other hematologic malignancies were included in the analysis.
Results from the analysis showed that only 22.7% of the pediatric leukemia patients were referred for genetic evaluation in the pediatric cancer predisposition clinic (CPP).
However, importantly, 25% of those who opted for genetic testing were found to have a CPS, indicating a significant detection rate in this subset of children.
Dr. Meade’s research team did not find any significant associations between a child's previous medical history, such as abnormal complete blood count (CBC) results before diagnosis or previous hematological visits, and a CPS diagnosis. This suggests that other factors, such as genetic predispositions, may play a significant role in the development of these conditions.
One of the study's key findings was that children with different types of leukemia and MDS tested positive for CPS. Moreover, CPS was found to be prevalent even in those patients without notable medical or family histories that might typically suggest a risk of CPS.
Current guidelines may contribute to under-reporting and identification of CPS, suggesting the necessity of making genetics evaluation and germline testing available to all pediatric leukemia patients, irrespective of their medical history.
Timely and accurate identification of individuals with CPS is crucial for long-term outcomes and survival, as the treatment and follow-up plans can be adjusted to fit their specific needs, while at the same time helping the rest of the family unit to understand their existing and potential familial risk for similar diagnoses.
Read the entire study using the reference link below.
Reference
D’Aquila KR, Kessler E, Cooper KL, Durst A, Meade J. Assessment of Factors Associated With the Evaluation of Children for Leukemia Predisposition Syndromes: A Retrospective Single-Center Study. J Pediatr Hematol Oncol. 2023 Mar 16. Online ahead of print.
Learn more about Dr. Meade and the Cancer Predisposition Syndrome Program at UPMC Children’s Hospital of Pittsburgh
