Predictors of CMV Reactivation and Survival in Adult Allogeneic HSCT Recipients without CMV Prophylaxis

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<h3>Introduction</h3> Cytomegalovirus (CMV) is a frequent infectious complication after allogeneic HSCT, with seropositive recipients demonstrating higher mortality in registry studies. Pre-emptive treatment (PET) strategies have widely been implemented universally, however with new prophylactic agents available, at-risk groups need to be identified to ensure CMV prophylaxis is appropriately targeted. <h3>Methods</h3> Retrospective single centre cohort study of all allogeneic HSCT from 2013-2018 inclusive. Patients were assessed for clinically significant CMV infection (cs-CMVi), visceral disease and survival at a 1-year landmark analysis based on CMV serostatus and donor type (sibling [Sib]/Matched Unrelated Donor [MUD]). CMV PCR was measured by IU/mL, cs-CMVi defined as >1000iu/mL and were treated with PET ganciclovir/valganciclovir, or foscarnet if neutropenic. All MUDs received either "Rutuu" protocol high dose prednisolone (pre 2015) or Thymoglobulin ATG 4.5mg/kg (2015 onwards). <h3>Results</h3> Of 173 consecutive adult alloHSCTs, cs-CMVi developed in 54% D-/R+ vs 30% D+/R+or- (P<0.0001, Table 1 and Fig 1). This effect was more profound when assessing donor type, with cs-CMVi in 67% D-/R+ MUDs vs 38% D+/R+or- MUDs, 31% D-/R+ Sibs and 27% D+/R+or- Sibs (P<0.01, Fig 2). Overall 1-year survival of D-/R+ MUDs was significantly less than D+/R+or- MUDs (46% vs 82%, P=0.01, Fig 3). cs-CMVi was also a predictor of overall survival with a 1-year survival of 42% D-/R+ MUDs if cs-CMVi vs 64% if no cs-CMVi and, 71% D+/R+or- MUDs if cs-CMVi vs 91% if no cs-CMVi (P=0.04, Fig 4). There were 11 (6.3%) patients with evidence of CMV disease, of which 4 were D-/R+ MUDs (4/27,15%) and 4 were D+/R+ MUDs (4/48, 10%). <h3>Conclusions</h3> In alloHSCT recipients without CMV prophylaxis, CMV serostatus and donor type are significant predictors of CMV reactivation and overall survival, with CMV D-/R+ MUDs the highest risk group for cs-CMVi and mortality, therefore potential candidates for CMV prophylaxis.