*Purpose: To evaluate efficacy and safety of valganciclovir for prevention of cytomegalovirus (CMV) after treatment of rejection with anti-lymphocyte depleting antibodies (ALA).

*Methods: This single-center retrospective study of adult kidney transplant recipients (KTR) compared incidence of CMV viremia after treatment of rejection with ALA in those who received antiviral prophylaxis with valganciclovir to those who did not. KTR who received either rabbit antithymocyte globulin (rATG) or rituximab for rejection at University Health between February 2017 and July 2020 were reviewed for inclusion. Efficacy and safety outcomes within 1 year of ALA were compared.

*Results: A total of 53 KTR with 64 rejection episodes (50% antibody-mediated, 9% T-cell mediated, 41% mixed) were included. The majority of recipients were Hispanic (60%) with median age 41 years (IQR 21-55), positive CMV IgG (60%), and ALA induction immunosuppression (83%). Most rejection episodes were treated with rATG (83%) at a median total 4 mg/kg dose. Most received valganciclovir prophylaxis (80%). More prophylaxis patients received rATG for ALA therapy (94% vs 38% p<0.01) whereas more no prophylaxis patients received rituximab (54% vs 9% p<0.01). There was no significant difference in incidence of CMV viremia or other outcomes between groups (Table 1). Although not statistically significant, incidence of leukopenia and neutropenia was higher in the prophylaxis group (55% vs 23% p=0.06 and 31% vs 8% p=0.16, respectively). Among six rejection episodes (occurring in five patients) associated with CMV viremia post-ALA therapy, three patients had donor IgG+/recipient IgG- CMV serology. CMV viremia occurred a median of 101 (IQR 53-204) days post-ALA. Breakthrough CMV viremia occurred in three of six cases while on appropriately-dosed valganciclovir prophylaxis.

*Conclusions: This is the first study to assess the efficacy of valganciclovir prophylaxis post rejection treatment. Overall, incidence of CMV viremia was low and use of valganciclovir prophylaxis after treatment of rejection with ALA was not associated with a decreased incidence of CMV viremia. There was numerically more leukopenia and neutropenia among KTR who received valganciclovir prophylaxis. With half of CMV viremias occurring while patients were receiving prophylaxis, and half of the patients being high risk CMV mismatches, the necessity and optimal duration for CMV prophylaxis after the treatment of rejection with ALA remains unclear. Prophylaxis should be instituted judiciously and may increase a patient’s risk for cytopenias.

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