CMV REACTIVATIONS IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT FROM HLA-MATCHED AND HAPLOIDENTICAL DONORS WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE.

BACKGROUND: Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Graft-versus-host disease prophylaxis (GVHD) with post-transplant cyclophosphamide (PTCy) is associated with an increased risk of CMV infections, with limited data on HSCT with PTCy assessing together matched sibling donors (MSD), matched unrelated donors (MUD), and haploidentical donors (HAPLO).

OBJECTIVES: Characterize CMV reactivation and recurrences, in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and HAPLO using PTCy as GVHD prophylaxis in the pre-letermovir era. Analyze risk factors of CMV reactivations, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections.

STUDY DESIGN: We analyzed CMV reactivations in patients undergoing HSCT from 160 MSD, 124 MUD and 82 HAPLO from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus and mycophenolate mofetil was given, irrespective of donor type.

RESULTS: Overall, 46% of patients had at least one CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for HAPLO donors (p<0.001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including HAPLO donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age and grade II-IV acute GVHD remained the adverse factors for second CMV reactivation in multivariate analysis, but not type of donor. The 1-year cumulative incidence of third reactivation from HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the hazard for NRM was superior for patients who had a CMV reactivation in multivariate time-dependent Cox-model analysis.

CONCLUSIONS: CMV reactivation is frequent in HSCT with PTCy among patients not receiving letermovir prophylaxis. Identified risk factors include the use of HAPLO donor, recipient CMV seropositivity, and acute grade II-IV GVHD. The prevalence of recurrent CMV reactivations pose a noteworthy issue, especially after acute GVHD, warranting trials for secondary prophylaxis strategies.