Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis

Abstract

Prior studies suggest increased CMV infection following haploidentical donor transplantation with post-transplant cyclophosphamide (HaploCy). The role of allograft source and PTCy in CMV infection and disease is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection as well as transplant outcomes as it relates to CMV serostatus and occurrence of CMV infection by d180. We examined patients reported to CIBMTR between 2012-2017 who had received HaploCy (n = 757), Sib with PTCy (SibCy, n=403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n=1605) for AML/ALL/MDS. Cumulative incidences of CMV infection by d180 were 42% (99% CI, 37-46), 37% (31 - 43), and 23% (20 - 26), respectively [p<0.001]. CMV end-organ disease was statistically comparable. CMV infection risk was highest for CMV-Seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor [HaploCy (n=545): HR 50.3 (14.4 - 175.2); SibCy (n=279): HR 47.7 (13.3 - 171.4); SibCNI (n=1065): HR 24.4 (7.2 - 83.1); p<0.001]. D+/R- patients also had increased risk for CMV infection. Among seropositive recipients or those developing CMV infection, HaploCy had worse OS and NRM. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic GVHD overall, but CMV infection in PTCy recipients was associated with higher cGVHD (p=0.006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally CMV infection may negate the cGVHD protection of PTCy. This study supports aggressive prevention strategies in all patients receiving PTCy.

Clinical impact of multiple DNA virus infections in nondepleted haploidentical and unrelated allogeneic hematopoietic stem cell transplantation

“…21,22 Recently, CIBMTR published an analysis comparing the incidence and impact of CMV infection in 757 patients who received haplo-HSCT with and demonstrated that PTCy, regardless of donor, is associated with higher incidence of CMV infection and, among those developing CMV infection, haplo-HSCT had worse OS and NRM. 23 The intense immunosuppression used in both types of transplants may explain these findings.…”

Cytomegalovirus in Haematological Tumours

“…PTCy, regardless of donor, was associated with a higher incidence of CMV infection. The study also concluded that CMV infection could negate the cGVHD protective benefit of PTCy ( 75 ).…”

CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update

“…PTCy is a method of in vivo T cell depletion that mainly acts on alloreactive T cells after haploSCT. CMV reactivation was noticed in 42%-69.2% of patients who underwent PTCy-haploSCT (51)(52)(53)(54)(55)(56)(57)(58). A total of 2.8%-4.5% of patients experienced CMV-associated disease (51,52).…”

“…CMV reactivation was noticed in 42%-69.2% of patients who underwent PTCy-haploSCT (51)(52)(53)(54)(55)(56)(57)(58). A total of 2.8%-4.5% of patients experienced CMV-associated disease (51,52). CMV reactivation occurred at a median time of 35-39 days (51,52,57).…”