Severe therapy‐related toxicities after treatment for Hodgkin lymphoma due to a pathogenic TERT variant and shortened telomeres

Abstract

Telomere biology disorders predispose affected individuals to specific malignancies and organ fibrosis in tissues sensitive to telomere length (TL) shortening, especially after exposure to chemotherapy and radiation. We report a case of a 17‐year‐old female with Hodgkin lymphoma who developed severe chemotherapy‐related toxicities. She was subsequently found to have peripheral blood lymphocyte TL < 1st percentile and a pathogenic variant in TERT inherited from her father. This case demonstrates that early genetic evaluation of patients who experience greater than expected therapy‐related toxicities may be warranted to help guide further decisions regarding therapy, imaging modalities, and lifelong cancer prevention surveillance.

Pathogenic Loss-of-Function Germline TERT Mutations in Patients With Solid Tumors

“… 5 Moreover, for patients with both obvious and subtle telomere syndromes, exquisite treatment sensitivities have been reported. 6 , 7 Although only one in 1,571 individuals in this series of patients with advanced cancer showed a germline TERT mutation, this could translate to more than 1,000 patients diagnosed with malignancies a year in the United States who may have increased therapeutic sensitivities. Because telomere syndrome disorders are complex and exhibit anticipation, incomplete penetrance, multiple genes that underpin disease, recognized modifiers, and both autosomal dominant and autosomal recessive patterns of inheritance, this estimate will be refined with time.…”

“… 2 - 5 The identification of patients with telomere syndromes is of significant clinical importance because these patients are exquisitely sensitive to alkylating chemotherapeutic agents and ionizing radiation. 6 - 8 …”