LACTIC ACIDOSIS AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION AND POSSIBLE INFLUENCE OF ANTIVIRAL DRUGS

A 53-year-old woman with a history of acute myeloid leukemia received a second allogenic hematopoietic stem cell transplant (HSCT) and was prescribed, among other medications, acyclovir and letermovir (480 mg daily oral dose) for prophylaxis of respectively herpes simplex and cytomegalovirus infection. The patient was admitted in the intensive care unit (ICU) for dyspnea and oliguria. Laboratory investigations revealed acute kidney injury, but also a severe and progressive lactic acidosis. Liver function tests were within normal range. The combination of lactic acidosis, hypoglycaemia and acylcarnitine profile in plasma suspected a mitochondrial toxicity. Letermovir therapy was interrupted and determination of plasma letermovir pharmacokinetics revealed a prolonged terminal half-life (40.7 h) that was not significantly influenced by continuous venovenous hemofiltration. Exploration for genetic polymorphisms revealed that the patient was SLCO1B1*5/*15 (c.521T>C homozygous carrier and c.388A>G heterozygous carrier) with a predicted non-functional OATP1B1 protein. The relationship between letermovir accumulation and development of lactic acidosis requires further observations.