Conversion from Cytomegalovirus Universal Prophylaxis with Valganciclovir to the Preemptive Monitoring Approach to Manage Leukopenia after Kidney or Pancreas Transplantation.

Jorgenson, Margaret R; Wong, Cynthia; Descourouez, Jillian L; Saddler, Christopher M; Smith, Jeannina A; Mandelbrot, Didier A

PURPOSE In clinical practice, conversion from universal cytomegalovirus prophylaxis (CMV PPX) with valganciclovir (VGC) to targeted therapy (preemptive monitoring, PEM) is often pursued in the setting of leukopenia. It is unknown if this is an effective strategy. METHODS Adult patients receiving a kidney and/or pancreas transplant were included if converted from PPX to PEM between 9/1/19-3/1/20 due to leukopenia. A positive CMV viral load (VL) was defined as CMV PCR greater than the lower limit of quantification (LLOQ) based on local lab testing. A CMV VL of >500 IU/mL was chosen as the preemptive treatment (PET) threshold. Primary objective was to describe the impact of conversion on resolution of leukopenia. Secondary objectives were to assess PEM associated outcomes. RESULTS There were 49 patients converted from PPX to PEM due to leukopenia in the study period; 88% were KTRs and 96% received lymphocyte-depleting induction. 84% were seropositive at transplant (R+) and 16% were high-risk (D+/R-). Mean WBC at time of enrollment was 1.4±0.4. After PEM conversion, WBC recovered to >3 in 87.8% of the population in a mean of 26.8±24.5 days. Immunosuppression was modified in 96% of the population and GCSF was required in 46.9% of patients. CMV viremia occurred in 36.7% of the population; 78% were KTRs and 94% were R+. Time from PEM enrollment to PET was 64±34 days. Median VL at first detection was 587 IU/mL, median peak was 1,920 IU/mL. Five patients (27.8%) presented with symptoms consistent with CMV syndrome, none had end organ disease. Six patients (33%) presented with a VL <500 IU/mL at first detection, but all subsequently surpassed the threshold and required PET. Mean duration of PET was 25±11 days. Mean change in WBC in response to PET was -0.4±1.3. Immunosuppression required further adjustment in 61% of patients. There were no deaths or graft loss due to CMV at last follow up. CONCLUSION In kidney and pancreas transplant recipients who undergo PEM conversion due to leukopenia, withholding of VGC can improve leukopenia, but other concomitant measures are necessary. This population should be considered fairly high risk, with a threshold of treatment of first quantifiable replication. Our findings suggest lack of harm from this approach, but highlight the importance of close monitoring to prevent symptomatic replication. Larger studies with longer follow up are needed to better evaluate the impact of PEM conversion on late-onset CMV and patient and graft outcomes.