Impact of CMV Reactivation on Clinical Outcomes Post Allogeneic Stem Cell Transplant in Patients with Sickle Cell Disease

Introduction Cytomegalovirus (CMV) reactivation post allogeneic hematopoietic stem cell transplantation (HCT) in patients with sickle cell disease (SCD) may increase the risk of graft failure (GF) and graft versus host disease (GVHD). However, the real impact of CMV reactivation in SCD patients has not been studied in isolation. Objective To describe the risks for and impact of CMV reactivation in SCD HCT. Method This multi-institutional retrospective study included all SCD patients who underwent allogeneic HCT between 2005-2022 at four sites. Descriptive statistics were used to analyze the data. Non-parametric statistics was used to compare clinical outcomes between groups based on presence or absence of CMV reactivation (CMVRe+ or CMVRe-). Results Ninety-seven patients (age range 1.8-25 years; 55% male) were included, majority underwent a matched sibling donor HCT (54%). Most HCT utilized a reduced intensity conditioning (RIC) regimen (62%) with either rabbit anti-thymocyte globulin (39%) or alemtuzumab (61%). Based on Donor (D) and Recipient (R) CMV seropositivity, 31 transplants were D+/R+, 14 were D-/R+, 28 were D+/R- and 21 were D-/R- with remaining 3 unknown. CMVRe+ occurred in 51% of patients at a median of day (D)+8 post-HCT (Range D-10 to D+113). Early reactivation (from start of conditioning to D+14) was observed in 72% (n=36) of patients. There was no difference in baseline characteristics between CMVRe+ (n=50) vs CMVRe- (n=47), except that CMVRe+ was observed in a significant proportion of R+ (79% vs 15%; p<0.001) and D+ patients (79% vs 46%; p <0.0012). Five (5.1%) patients received letermovir (all R+) with four reactivating CMV. The incidence of other viral reactivations was significantly higher in the CMVRe+ group (54% vs 34%; p=0.048). There was no difference between the groups (CMVRe+ vs CMVRe-) for the incidence of GF (12% vs 8.9%, p=0.07), acute GVHD ( 9% vs 13%, p=0.3) and chronic GVHD (11 vs 15%, p=0.3). Similarly the recovery of absolute lymphocyte count (> 500 cells/cu.mm) and CD4 count (> 50 cells/cu.mm) at D+100 was similar between both groups. There was significant association of CMVRe+ and whole blood (WB) donor chimerism (DC) (p=0.006) with mixed chimerism (MC) in WB (< 95% donor) occurring in 43% CMVRe+ vs 21% CMVRe- patients. Although this observed again at D+365 it was non-significant (p=0.051); with MC in 39% of CMVRe+ vs 21% of CMVRe- groups. At a median follow up of 3.4 years (range 0.5-5.31) from HCT there was only one death in the CMVRe+ cohort and none in the CMVRe- cohort. Conclusion As anticipated in our study, R+ and D+ increased the risk for CMV reactivation, with majority occurring in the pre-engraftment period. With the bulk of SCD patients receiving RIC, CMV was a significant factor contributing to the development of MC at D+180. Further analysis of outcomes after adjusting for confounding factors are underway.