*Purpose: Kidney transplant recipients (KTRs) who receive antiproliferative agents for immunosuppression and valganciclovir for CMV prophylaxis are at high risk of developing leukopenia and neutropenia. Limited data exist on the extent to which this results in a dose reduction or discontinuation of mycophenolate acid and/or valganciclovir.

*Methods: This is a retrospective cohort study of 573 KTRs at University of California, San Francisco Medical Center between 2012 and 2018, who were CMV mismatched (D+/R-) or had a PRA > 80%. Individuals with HIV, Hepatitis B and C, and primary non-function were excluded. KTRs were followed for > 1-year post-transplant. Neutropenia and leukopenia were defined as an absolute neutrophil count < 1000 cells/microliter and an absolute white blood cell count < 3500 cells/microliter, respectively. Cox proportional hazards regression models using leukopenia or neutropenia as a time-varying predictor were used to determine the risk of mycophenolate acid and valganciclovir dose reduction or discontinuation and use of granulocyte colony stimulating factor (G-CSF). Models were adjusted for recipient demographics, transplant characteristics, and duration of valganciclovir prophylaxis.

*Results: Study cohort consisted of 233 and 379 KTRs who were CMV mismatched and/or were highly sensitized, respectively. Mean follow-up was 3.7 (SD, 1.8) years. The mean age of the cohort was 50.4 (13.1) years and 57.6% were female. A total of 468 (81.7%) of the participants had leukopenia, 208 (36.3%) had neutropenia and 108 (18.8%) had CMV viremia. Neutropenia modeled as a time varying predictor was associated with an increased risk of both valganciclovir [adjusted hazard ratio, aHR: 13.0, 95% CI: 7.9-21.6] and mycophenolate acid [aHR 10.8, 95% CI: 6.9-17.0] discontinuation. Neutropenia was also associated with more G-CSF use [aHR 45.5, 95% CI: 27.9-74.0] and hospitalizations [aHR 3.3, 95% CI: 2.1-5.1]. Similar findings were shown for leukopenia.

*Conclusions: Leukopenia and neutropenia occur frequently after kidney transplantation in patients who are CMV mismatched or highly sensitized, and this leads to discontinuation of mycophenolate acid and/or valganciclovir and increases the utilization of G-CSF. Early modification of antiproliferative immunosuppression and/or antiviral drugs for CMV may lead to long-term adverse outcomes.

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