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

Abstract

Prior studies suggest increased cytomegalovirus (CMV) infection after haploidentical donor transplantation with posttransplant cyclophosphamide (HaploCy). The role of allograft source and posttransplant cyclophosphamide (PTCy) in CMV infection is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection, and effects of serostatus and CMV infection on transplant outcomes. We examined patients reported to the Center for International Blood and Marrow Transplantation Research between 2012 and 2017 who had received HaploCy (n = 757), matched related (Sib) with PTCy (SibCy, n = 403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n = 1605). Cumulative incidences of CMV infection by day 180 were 42%, 37%, and 23%, respectively (P < .001). CMV 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]: hazard ratio [HR], 50.3; SibCy [n = 279]: HR, 47.7; SibCNI [n = 1065]: HR, 24.4; P < .001). D+/R- patients also had increased risk for CMV infection. Among R+ or those developing CMV infection, HaploCy had worse overall survival and nonrelapse mortality. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic graft-versus-host disease (GVHD) overall, but CMV infection in PTCy recipients was associated with higher chronic GVHD (P = .006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally, CMV infection may negate the chronic GVHD protection of PTCy. This study supports aggressive prevention strategies in all receiving PTCy.

• Authors: Scott R Goldsmith, Muhammad Bilal Abid, Jeffery J Auletta, Asad Bashey, Amer Beitinjaneh, Paul Castillo, Roy F Chemaly, Min Chen, Stefan Ciurea, Christopher E Dandoy, Miguel Ángel Díaz, Ephraim Fuchs, Siddhartha Ganguly, Christopher G Kanakry, Jennifer A Kanakry, Soyoung Kim, Krishna V Komanduri, Maxwell M Krem, Hillard M Lazarus, Hongtao Liu, Per Ljungman, Richard Masiarz, Carolyn Mulroney, Sunita Nathan, Taiga Nishihori, Kristin M Page, Miguel-Angel Perales, Randy Taplitz, Rizwan Romee, Marcie Riches
• Journal: Blood (Blood) Vol. 137 Issue 23 Pg. 3291-3305 (06 10 2021) ISSN: 1528-0020 [Electronic] United States
• PMID: 33657221 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclophosphamide

Topics

• Adolescent
• Adult
• Aged
• Allografts
• Child
• Child, Preschool
• Chronic Disease
• Cyclophosphamide (administration & dosage, adverse effects)
• Cytomegalovirus
• Cytomegalovirus Infections (chemically induced, mortality)
• Disease-Free Survival
• Female
• Graft vs Host Disease (drug therapy, metabolism)
• Hematopoietic Stem Cell Transplantation
• Humans
• Incidence
• Male
• Middle Aged
• Survival Rate