Infectious complications after hematopoietic stem cell transplantation: current status and future perspectives in Korea

Cho, Sung-Yeon; Lee, Hyeon-Jeong; Lee, Dong-Gun

Currently available anti-CMV agents in Korea are ganciclovir, valganciclovir, foscarnet, and cidofovir. Since February 2018, the use of valganciclovir in HSCT patients with CMV infection has increased due to changes in the reimbursement rules. Regarding adverse events, attention should be paid to bone marrow suppression, and in patients with renal insufficiency. GVHD or the use of www.kjim.org https://doi.org/10.3904/kjim.2018.036 monoclonal antibodies (i.e., alemtuzumab) can increase the incidence of CMV infections. Such infections may not be distinguishable from GVHD, or may coexist with GVHD, and may not respond to antiviral drugs if diagnosis is delayed [93] . If there is persistent infection despite anti-CMV therapy, CMV refractoriness can be considered if a > 1 log 10 decrease in CMV DNA level in blood or plasma is not achieved after ≥ 2 weeks of treatment. In CMV-refractory cases, resistance should also be suspected. Although CMV resistance remains uncommon in HSCT recipients from HLA-matched donors (0% to 7.9%), in high-risk patients, the incidence of CMV resistance is up to 14.5% [94] [95] [96] . The gold standard of CMV resistance testing is an increase in the IC 50 (half maximal inhibitory concentration) value by plaque reduction assay. However, CMV resistance can be defined when one or more genetic mutations associated with ganciclovir, valganciclovir, foscarnet, and cidofocir are identified with clinical refractoriness. Therefore, in recent years, mutations in UL97 and UL54 can be tested. Predisposing factors for CMV resistance include prolonged use of anti-CMV agents, recurrent CMV infections, inadequate antiviral absorption, subtherapeutic antiviral level, haploidentical transplantation, or T-cell depletion [97] . If resistance is confirmed, a drug to which resistance has not been identified, or combination of drugs, may be used, but treatment is currently limited. Clinician's experience is important in such complicated cases.