Evaluation of an Intensive Strategy to Decrease CMV Reactivation in Haploidentical Stem Cell Transplant Patients Compared to the Traditional Approach

Introduction: Cytomegalovirus (CMV) infection can increase the morbidity and mortality associated with allogeneic hematopoietic stem cell transplantation (HSCT).  Due to a higher degree of immunosuppression, haploidentical transplants can be at an increased risk of viral infections, particularly CMV.  

Methods: In a retrospective review of haploidentical HSCT patients, we compared a traditional antiviral prophylaxis regimen with an intensified approach to determine whether a more intensive strategy could decrease rates of CMV reactivation.  CMV reactivation rates between the two groups were compared using Fischer’s exact test. The median time to reactivation and engraftment were compared using the Mann-Whitney U test. A Kaplan-Meier survival curve was utilized for non-relapse mortality (NRM) and patient groups were compared using the log-rank statistic.

Results: A total of 84 patients underwent haploidentical HSCT from 3/2009 through 5/2013. Patients were excluded due to the following: donor and recipient negative serostatus (n=7), CMV reactivation prior to day 0 (n=3), second transplant (n=7), or use of other antiviral therapy during the first 100 days for non-CMV infections (n=4).  The median follow up for the remaining 63 patients was 295 days (range 7 – 1473). Patients received valacyclovir 500 mg orally daily starting on day -1 (n=26) or either valganciclovir 900 mg orally twice a day or ganciclovir 5 mg/kg IV twice daily from admission through day -2 followed by traditional or high dose valacyclovir (n=37). Upon CMV reactivation, preemptive therapy was commenced in both groups. Baseline characteristics were similar between the groups and all patients received conditioning chemotherapy with fludarabine and melphalan +/- TBI 200 cGy or thiotepa, as previously described.  CMV reactivation prior to day 100 was lower in the intensive strategy group compared to the traditional strategy although not significant (68% vs. 85%; p= 0.15). Median time to CMV reactivation was not significant between the traditional and intensive groups (31 days vs. 33 days; p =0.13). A difference in median time to engraftment was not evident (18 days vs. 18 days; p=0.72). One patient in each group had primary graft failure. Non-relapse mortality did not differ between the groups [HR 0.75 (0.25, 2.22); p=0.6].  

Conclusion: A trend towards decreased CMV reactivation and longer time to reactivation was seen with an active CMV regimen prior to day 0 in haploidentical HSCT patients. Although currently underpowered, data collection is ongoing.