Update on Recommendations for Surveillance for Children with Predisposition to Hematopoietic Malignancy.

in Clinical cancer research : an official journal of the American Association for Cancer Research by Luke D Maese, Marcin W Wlodarski, Sun Young Kim, Alison A Bertuch, Gaëlle Bougeard, Vivian Y Chang, Lucy A Godley, Payal P Khincha, Roland P Kuiper, Harry Lesmana, Rose B McGee, Lisa J McReynolds, Julia Meade, Sharon E Plon, Sharon A Savage, Sarah R Scollon, Hamish S Scott, Michael F Walsh, Kim E Nichols, Christopher C Porter

TLDR

  • Children with certain gene changes have a higher risk of developing a type of blood cancer called myelodysplastic syndrome (MDS) or other types of blood cancer called leukemias and lymphomas. Some of these gene changes are inherited from their parents, while others can happen later in life. Researchers have found that early intervention through a procedure called hematopoietic stem cell transplantation (HSCT) can help improve the chances of survival for children with these gene changes. However, not all children with these gene changes will develop cancer, so it's important to closely monitor them for any signs of cancer. Researchers have developed personalized recommendations for monitoring children with these gene changes based on their genetic profile. These recommendations include regular check-ups, education about the signs and symptoms of cancer, and consultation with experienced doctors. As more research is done, these recommendations will continue to evolve to better manage these conditions.

Abstract

Children with certain germline gene variants have an increased risk of developing myelodysplastic syndrome (MDS) and other hematopoietic malignancies (HM), such as leukemias and lymphomas. Recent studies have identified an expanding number of these predisposition genes, with variants most prevalent in children with MDS but also found in other HM. For some hematopoietic malignancy predisposition (HMP) disorders, specifically those with a high risk of MDS, early intervention through hematopoietic stem cell transplantation (HSCT) can favorably impact overall survival, providing a rationale for rigorous surveillance. A multidisciplinary panel of experts at the 2023 AACR Childhood Cancer Predisposition Workshop reviewed the latest advances in the field and updated prior 2017 surveillance recommendations for children with HMP. In addition to general guidance for all children with HMP, which includes annual physical examination, education about the signs and symptoms of HM, consultation with experienced providers, and early assessment by an HSCT specialist, the panel provided specific recommendations for individuals with a higher risk of MDS based on the affected gene. These recommendations include periodic and comprehensive surveillance for individuals with those syndromes associated with higher risk of MDS, including serial bone marrow examinations to monitor for morphologic changes and deep sequencing for somatic changes in genes associated with HM progression. This approach enables close monitoring of disease evolution based on the individual's genetic profile. As more HMP-related genes are discovered and the disorders' natural histories are better defined, these personalized recommendations will serve as a foundation for future guidelines in managing these conditions.

Overview

  • The study focuses on the increased risk of myelodysplastic syndrome (MDS) and other hematopoietic malignancies (HM) in children with certain germline gene variants. The methodology includes a review of the latest advances in the field and updating of prior 2017 surveillance recommendations for children with hematopoietic malignancy predisposition (HMP) by a multidisciplinary panel of experts. The primary objective is to provide personalized recommendations for individuals with a higher risk of MDS based on their genetic profile for close monitoring of disease evolution.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions, specifically early intervention through hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancy predisposition (HMP) disorders with a high risk of MDS. The key findings suggest that early intervention through HSCT can favorably impact overall survival, providing a rationale for rigorous surveillance. The study identifies specific recommendations for individuals with a higher risk of MDS based on their genetic profile, including periodic and comprehensive surveillance for individuals with syndromes associated with higher risk of MDS, including serial bone marrow examinations to monitor for morphologic changes and deep sequencing for somatic changes in genes associated with HM progression.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they provide personalized recommendations for managing hematopoietic malignancy predisposition (HMP) disorders with a higher risk of myelodysplastic syndrome (MDS). The study identifies limitations, such as the need for more research on the natural histories of these disorders and the potential for false negatives in surveillance. Future research directions include exploring the use of next-generation sequencing and artificial intelligence for more accurate and efficient surveillance, as well as investigating the potential benefits and risks of HSCT for individuals with HMP disorders.
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