"Low Dose Ganciclovir for Cytomegalovirus Reactivation after Allogeneic HSCT Is a Feasible Option with Same Efficacy and Less Toxicity Than Regular Dose"

Background: Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) occurs in approximately 70% of seropostive patients. CMV reactivation is associated with higher non-relapse mortality (NRM) and worse overall survival (OS). Although preemptive therapy effectively prevents CMV disease, toxicity of ganciclovir (GCV), valganciclovir (VGCV), and foscarnet is a major concern. While GCV 5 mg/kg BID (regular dose) is the most commonly used regimen, some series have suggested that a lower dose (5mg/kg QD, lower dose) could be an option. Objectives: To compare two different regimens of ganciclovir (regular vs. lower dose) for preemptive CMV therapy. Patients and Methods: This was an observational, retrospective study in adult patients who underwent HSCT between April 2007 and April 2020 in two centers. Doses of ganciclovir were determined at the discretion of the transplant physician. The primary endpoint was CMV clearance (rate and time to) between the two preemptive strategies. Results: We analyzed 118 consecutive patients. The median age was 50 years, acute leukemia was the most frequent underlying disease (59%), and most patients received transplants from alternative donors (matched unrelated in 32% and haploidentical in 36%), after reduced-intensity conditioning regimens (76%), with peripheral blood as the source of stem cells (73%). T-cell depletion was performed in 31% (ATG in 29%, alemtuzumab in 2%). In total there were 174 CMV reactivations: 124 (71%) were treated with the regular dose, and 50 (29%) in an outpatient setting with low dose. The median time to CMV clearance was similar between regular and low dose of GCV (15 days vs. 18 days, respectively, p=0.88). The cumulative incidence (CI) of CMV clearance at 30 days was 83% in the regular dose and 88% in the lower dose (p=0.82). By multivariate analysis, correcting for the differences between the groups, the GCV regimen did not influence the time to CMV clearance (hazard ratio 0.94, 95% confidence interval 0.70 - 1.26). On the other hand, hematologic toxicity was more frequent in the regular dose, with more cases of both grade 3-4 neutropenia (59% vs. 33%, respectively, p=0.002) and thrombocytopenia (77% vs. 48%, respectively, p<0.0001). Ten patients had CMV disease and were treated with GCV 5mg/kg BID for 21 days. Conclusion: Our findings suggest that the use of GCV once daily was safe, less toxic, and may be less expensive, considering that most patients will receive the regimen in an outpatient basis. These data should be confirmed in a prospective trial.