Jochen J Frietsch1*, Detlef Michel2*, Thomas Stamminger2, Friederike Hunstig1, Sebastian Birndt1, Ulf Schnetzke1, Sebastian Scholl1, Andreas Hochhaus1 and Inken Hilgendorf1.
* Both authors contributed equally.
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associated tissue-invasive disease is associated with a considerable
risk of morbidity and mortality after allogeneic hematopoietic stem
cell transplantation (HSCT). Recently, the terminase inhibitor
letermovir (LMV) has been approved for prophylaxis of CMV infection in
HSCT. We hereby report a 60-year-old female experiencing CMV
reactivation after HSCT in a CMV seronegative donor-constellation. Due
to ongoing elevated CMV viral load and drug-associated
myelosuppression, which prevented ganciclovir therapy, treatment was
replaced by foscarnet. Due to nephrotoxicity, foscarnet was switched to
LMV. The patient developed skin GvHD and prednisolone was started.
Subsequently, CMV viremia worsened despite LMV therapy. Genotyping
revealed the mutation C325Y of the CMV UL56 terminase being associated
with high-level resistance against LMV. Prolonged uncontrolled
low-level viremia due to prednisolone treatment may have favored the
selection of drug-resistant CMV. Despite the excellent toxicity profile
of LMV, physicians should be aware of risk factors for the emergence of
|Figure 1. Clinical course of the patient. Cytomegalovirus (CMV) copy numbers in folds of 105 in gray shown as drawn through line; administration of hyperimmune globulines (IVIG), cyclosporine (CsA), prednisolone, rituximab (depicted by crosses) and antiviral medication (ACV: acyclovir; FOS: foscarnet; GCV: ganciclovir; LMV: letermovir; VACV: valacyclovir) as indicated above, dectection of UL56 wild type (WT) is depicted as empty circle and UL56 C325Y as black circle respectively.|
Discussion and Conclusion