Germline assessment for alloHSCT candidates over 50 years: A 'Fast-Track' screening in myeloid neoplasms

Br J Haematol. 2024 Aug;205(2):503-509. doi: 10.1111/bjh.19460. Epub 2024 Apr 19.

Abstract

Patients aged 50 or above diagnosed with myeloid neoplasms (MNs) are typically not candidates for germline testing. However, approximately 8% carry pathogenic germline variants. Allogeneic haematopoietic stem cell transplantation (alloHSCT) remains an option for those aged over 50; neglecting germline testing could mask the risk for relative donor cell-derived MN. We propose a germline-augmented somatic panel (GASP), combining MN predisposition genes with a myeloid somatic panel for timely germline variant identification when initial testing is not indicated. Out of our 133 whole-exome-sequenced MN cases aged over 50 years, 9% had pathogenic/likely variants. GASP detected 92%, compared to 50% with somatic-only panel. Our study highlights the relevance of germline screening in MN, particularly for alloHSCT candidates without established germline-testing recommendations.

Keywords: HSC transplantation; genetic testing; germline predisposition; myeloid neoplasms.

MeSH terms

  • Aged
  • Exome Sequencing
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Germ-Line Mutation*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / genetics
  • Transplantation, Homologous