LAUSR

Persisting cytomegalovirus (CMV) DNAemia in spite of appropriate antiviral therapy is a risk factor for CMV disease and non-relapse mortality in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT) [1], and may be due to a lack of adequate expansion of functional CMVspecific T cells in response to viral replication (clinical resistance), to the emergence of antiviral resistant strains carrying specific point mutations or deletions within the sequence of the viral genes UL97, UL54 (virological resistance) or both [2, 3]. Currently, there is no consensus on when antiviral CMV resistance should be suspected and genotypic drug resistance testing be ordered. Several indicators reflecting therapeutic refractoriness have been proposed: [3–5] increase in CMV DNA load >20% (inter-assay coefficient of variation of the real-time PCR assays used) after 2 weeks of adequate treatment (Group 1), increase in CMV DNA load >0.5 log10 (Group 2) or >1 log10 (Group 3) after 2 weeks of treatment, and decrease in CMV DNA load <1 log10 after 2 (Group 4) or 2 (Group 5) weeks of treatment, in all categories with respect to CMV DNA load at the time of treatment initiation. In this study, refractory CMV DNAemia met one or more of the above criteria. A total of 203 patients who underwent allo-HSCT between January 2010 and June 2017 were included in this retrospective observational study. The median age of patients was 55 years (range, 18-69 years). Plasma CMV DNA load was monitored as previously indicated [6], using the CMV PCR Kit or the CMV RealTime CMV PCR (both from Abbott Molecular, Des Plaines, IL, USA). Antiviral therapy with (val)ganciclovir or foscarnet at conventional doses was initiated when the plasma CMV DNA load reached levels of >1500 IU/ml, or when the CMV dt was ≤2.0 days, whatever occurred first (this latter strategy since May 2014) [7]. A total of 147 patients had CMV DNAemia within the first year after allo-HSCT (cumulative incidence, 72.38%; 95% CI, 67.80%–76.41%), of whom 79 developed a single episode and 68 experienced one or more recurrences. The total number of episodes of CMV DNAemia was 246, of which 123 (50%) occurring in 96 patients required antiviral therapy (Table 1). (Val)ganciclovir was the first-choice drug in 110 episodes, whereas the remaining 13 episodes were initially treated with foscarnet. Switching of antiviral therapy was done in 30 episodes due either to hematological toxicity (n= 19) or to CMV DNAemia persistence through 3–4 weeks after treatment inception (n= 11). Out of the 123 treated episodes, 113 eventually cleared; the remaining 10 were still ongoing at the time of patient’s death. A total of 14 episodes in 14 patients (11.3%) were deemed to be refractory (Table 2). Specifically, 9, 3, 2, 12, and 6 episodes met Group 1, 2, 3, 4, and 5 criteria, respectively. Most of these were first episodes that occurred within the first 100 days after allo-HSCT and were initially treated with (val)ganciclovir. The CMV-serostatus pair D −/R+ and the occurrence of grades II–IV acute GvHD, both known factors associated with protracted or severely impaired reconstitution of CMV-specific T-cell immunity [2], were overrepresented in these episodes. Regretably, the * David Navarro [email protected]