A 5-year old girl with liver transplant was scheduled for a therapy including high-dose cytarabine for her Burkitt lymphoma. Cytarabine pharmacogenetics focus on cytidine deaminase (CDA) , the polymorphic liver enzyme responsible for its detoxification. Preliminary double testing for her CDA status on DNA lymphocytes showed none of the germline polymorphisms usually associated with CDA deficiency (ie, 79A>C (K27Q), 208G>A), but surprisingly with a functional mild deficiency syndrom. Despite 30% reduction in cytarabine dosing, life-threatening toxicities showed quickly and treatment was discontinued. Genetic HRM-based investigations performed in the patient on liver biopsy failed in generating a clear genotype. Further HRM+sequencing retrospective investigations on liver biopsy collected from the donor showed that he was actually bearing the homozygous CDA*2 allelic variant (ie, 79AA), a genotype usually associated with severe CDA deficiency. Based upon the donor liver genotype, and not the recipient genotype, treatement was resumed with further dose reduction, close monitoring and better tolerance eventually. The patient is now in complete remission more than a year after completion of the treatment. This case report illustrates the limits and risks of searching germline polymorphisms in patients with liver transplant when the story plays in the liver.
Citation Format: Cindy Serdjebi, Raphaelle Fanciullino, Frederic Fina, Arnaud Verschuur, Bertrand Roquelaure, Bruno Lacarelle, L'Houcine Ouafik, Joseph Ciccolini, Nicolas André. Recipient-donor contradictory genotype with impact on anticancer drug pharmacogenetics after liver transplant: A deadly gift. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5549. doi:10.1158/1538-7445.AM2014-5549