Failure of pre-emptive treatment of cytomegalovirus infections and antiviral resistance in stem cell transplant recipients

BACKGROUND Treatment of cytomegalovirus (CMV) infections after stem cell transplantation (SCT) does not always lead to a rapid viral response. The causes of treatment failure may be either viral resistance or immunological failure to control viral replication. This study investigated the response to pre-emptive treatment in CMV infections in order to define risk factors for treatment failure, including the role of antiviral resistance. METHODS Adult recipients of allogeneic T-cell depleted SCT were studied retrospectively (n=92). CMV infections were treated with (val)ganciclovir according to a CMV DNA-load-based pre-emptive strategy. Treatment failure was defined as a CMV DNA load of 1,000 copies/ml or more after at least 2 weeks of treatment. Resistance was analysed by nucleotide sequence analysis of the UL97 and UL54 genes in the first CMV DNA-positive sample and in samples during treatment failure. RESULTS Treatment failure occurred in 26 of the 47 pre-emptively treated patients (55%) and in 39 of 86 (45%) treatment episodes. The risk of treatment failure was increased during first treatment episodes (P=0.01) and during the use of immunosuppressive medication (P=0.02). Antiviral resistance was found in only 1 patient (4%) with treatment failure. CONCLUSIONS A slow response to pre-emptive antiviral treatment occurred frequently in CMV infections in SCT recipients. Antiviral resistance was observed but played a minor role in treatment failure.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease