Brincidofovir (CMX001) Toxicity Associated With Epithelial Apoptosis and Crypt Drop Out in a Hematopoietic Cell Transplant Patient: Challenges in Distinguishing Drug Toxicity From GVHD.

Journal of Pediatric Hematology/oncology
Claire J DetweilerDiana M Cardona

Abstract

Brincidofovir (CMX001) is an oral agent with activity against double-strand DNA viruses undergoing clinical trials in immunocompromised patients. We report a patient clinically diagnosed with brincidofovir-related gastrointestinal (GI) toxicity and his histologic findings. A 2-year-old boy with medulloblastoma undergoing autologous hematopoietic cell transplantation developed adenovirus viremia 9 days posttransplant. After initial treatment with intravenous cidofovir he was started on oral brincidofovir as part of a clinical trial. He developed hematochezia, anorexia, and emesis 11 weeks later. Sigmoid colon biopsy showed marked crypt drop out, moderate epithelial apoptosis, and lamina propria edema. The pathologic diagnosis was drug-related injury versus infection. Brincidofovir toxicity was diagnosed clinically and the drug was discontinued. His GI symptoms improved in 2 weeks with supportive care and octreotide. Brincidofovir causes GI toxicity and histologically demonstrates epithelial apoptosis and crypt injury, similar to graft versus host disease and mycophenolate mofetil toxicity.

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Citations

Nov 28, 2018·Expert Opinion on Drug Metabolism & Toxicology·Barbara DeleenheerJohan Maertens
May 23, 2019·Current Opinion in Infectious Diseases·Diana F Florescu, Erica J Stohs
Oct 1, 2019·Current Opinion in Infectious Diseases·Natalie J M Dailey GarnesAya Aboulhosn
Sep 2, 2018·Der Pathologe·H Bläker
Jan 29, 2019·Frontiers in Microbiology·Cécile Pochon, Sebastian Voigt
Aug 21, 2020·Antimicrobial Agents and Chemotherapy·Karoly TothTerry L Bowlin
Oct 8, 2018·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Francisco M MartyUNKNOWN SUPPRESS Trial Clinical Study Group
Aug 28, 2020·Microorganisms·Bratati Saha, Robin J Parks
Aug 10, 2020·Antiviral Research·Maud SalmonaJérôme LeGoff

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Methods Mentioned

BETA
biopsies
PCR
PCRs
biopsy

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