1. 6-Month Universal CMV Prophylaxis - Safety and Efficacy in Kidney Transplant Patients Induced with Alemtuzumab: A Single Center Retrospective Study Lakshmi Nadimpalli, MD, 1,2 Bing Ho, MD, 1,2,4 Brittany Lapin, MPH, 2,4 Pranav Dalal, MD, 1,2 John Friedewald, MD, 1,2,4 Aaron Kamauu, MD MS MPH, 5 Mark Loveless, MD MHA, 6 Robert Hoop, MPH, 7 Daniela P. Ladner, MD, 2,4 Michael G. Ison, MD MS FIDSA 2-4 Divisions of 1 Nephrology and Hypertension, 2 Organ Transplantation and 3 Infectious Diseases, Northwestern University Feinberg School of Medicine and 4 Northwestern University Transplant Outcomes Research Collaboration, Chicago, IL; 5 Anolinx LLC, Salt Lake City, Utah; 6 Oregon Health and Science University, Portland, OR; 7 Genentech, South San Francisco, CA ABSTRACTRESULTS METHODS CONCLUSIONS REFERENCES BACKGROUND Universal valganciclovir prophylaxis of kidney transplant patients has reduced the incidence of cytomegalovirus (CMV) but is associated with neutropenia as the most common adverse effect. Valganciclovir prophylaxis has not been studied in the setting of alemtuzumab induction. Electronic medical records of 1,134 kidney transplant patients who received both alemtuzumab and valganciclovir prophylaxis at Northwestern Memorial Hospital (1/1/2006 – 12/31/2012) were retrospectively reviewed. The average duration of prophylaxis was 177 days. Based on Kaplan-Meier estimates at 1 year: 10.2% had CMV viremia 2.8% had biopsy-proven CMV disease 46.5% developed neutropenia (ANC ≤1000 c/mL) 25.4% developed severe neutropenia (ANC ≤ 500 c/mL) 39.5% required at least a single dose of G-CSF Compared to prior studies, rates of neutropenia, severe neutropenia and use of G-CSF were higher, while rates of CMV viremia and pathology-diagnosed CMV disease were lower in this population that received alemtuzumab induction as compared to patients in historical studies that included few patients with alemtuzumab induction. The authors declare no conflict of interest regarding this poster. This study was supported by a grant from Anolinx. Valganciclovir is safe and effective for the prevention of CMV following kidney transplant 1 A recent study comparing 100 to 200 days of valganciclovir favored the longer duration of prophylaxis 2 o The incidence of leukopenia was 38% in the 200-day group and 26% in the 100-day group o 4% of patients in the 200-day group had discontinuation of valganciclovir secondary to leukopenia o 14% of cases of leukopenia were grade 3 or 4 o G-CSF was required in ~13% Leukopenia occurs in ~30% of transplant recipients who received alemtuzumab for induction 3 There is limited data on the safety and efficacy of 6 months of valganciclovir for the prevention of CMV among kidney transplant recipients who received alemtuzumab for induction Demographic Data Time to Cytomeglovirus through 12 months Time to Neutropenia through 12 months Kidney Transplant Sub-Cohort N=1134 #% Age <65 years98286.6% ≥65 years15213.4% Mean (Standard Deviation)49.83 (12.96) Median (Min – Max)51.00 (18 – 84) Sex = Male67959.9% Race/Ethnicity White, non-Hispanic43838.6% Black, non-Hispanic22419.8% Hispanic17815.7% Other413.6% Unknown25322.3% Number of follow-up years status-post transplant ≤1 year433.8% 1-2 years37032.6% 2-4 years40836.0% >4 years31327.6% Transplant Type Deceased Donor49944.0% Living Donor 63156.0% Baseline serum creatinine level (mg/dL) Mean (Standard Deviation)1.23 (0.55) Median (min – max)1.14 (0.08 – 9.48) Patients who received valganciclovir prophylaxis post- transplant Mean (SD) Duration (days)180.5 (201.0) Median Duration180.0 Received Tacrolimus 112399.0% Received Mycophenolate 111698.4% Figure 1a. Kaplan-Meier plot of time to CMV viremia through 12 months post-transplant Figure 1b. Kaplan-Meier Plot of time to biopsy-proven CMV disease through 12 months post-transplant Figure 2b. Kaplan-Meier Plot of severe neutropenia (ANC ≤ 500c/mL) within 12 months post-transplant Figure 2a. Kaplan-Meier Plot of any neutropenia (ANC ≤ 1000c/mL) within 12 months post-transplant Figure 2c. Kaplan-Meier Plot of first G-CSF use within 12 months post-transplant Viremia at 3- Month Viremia at 6- Month Viremia at 12- Month 2.7%4.8%10.2% Pathology Proven CMV Disease at 3M Pathology Proven CMV Disease at 6M Pathology Proven CMV Disease at 12M 0.5%0.8%2.8% Neutropenia at 3-Month Neutropenia at 6-Month Neutropenia at 12-Month 18.7%39.6%46.5% Severe Neutropenia at 3-Month Severe Neutropenia at 6-Month Severe Neutropenia at 12-Month 8.5%21.3%25.4% G-CSF Use at 3-Month G-CSF Use at 6-Month G-CSF Use at 12-Month 15.1%33.9%39.5% A retrospective cohort of patients who received a kidney transplant at Northwestern Memorial Hospital o From 1/1/2006 to 12/31/2012 o Received at least one dose of alemtuzumab o Received at least 3 months of valganciclovir prophylaxis Efficacy outcomes: Incidence of CMV viremia and tissue invasive CMV disease at 3, 6 and 12 months. Safety outcomes: Incidence of neutropenia, severe neutropenia and neutropenia requiring G-CSF at 3,6 and 12 months. Graft survival at 1, 3 and 5 years post-transplant. 6 months of valgancyclovir prophylaxis in this population of kidney transplant recipients that also received alemtuzumab induction is associated with: o Increased incidence of neutropenia compared to historic studies which included few patients with alemtuzumab induction (42.8% vs 15%) 2  Severe neutropenia (ANC < 500) was observed in 25.4% of patients at 1 year.  G-CSF was administered in 39.5% of patients at year. o Significantly lower incidence of CMV viremia (8.4% vs 37.4%) 2 at 12 months in the D+/R- cohort. o Incidence of tissue invasive CMV disease at 12 months  2.8% in the entire population  7.7% in the D+/R- subcohort  There was no CMV viremia or biopsy-proven CMV disease in the D-/R+ subcohort. o Graft retention rate at 1 year was 95.6% 1.Razonable RR, Humar A and the AST ID Community of Practice. Cytomegalovirus in Solid Organ Transplantation. Am J Transplant. 2013;13:s93-s106. 2.Humar A, Lebranchu Y, Vincenti F, Punch J, Abramowicz D, Blumberg E et al. The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am J Transplant. 2010; 10: 1228-1237. 3.Walker JK, Scholz LM, Scheetz MH, Gallon LG, Kaufman DB, Rachwalski EJ et al. Leukopenia complicates cytomegalovirus prevention after renal transplantation with alemtuzumab induction. Transplantation. 2007;83(7):874-882. Kaplan-Meier Estimates ViremiaColitis 6-Month2.1%2.0% 9-Month3.6%4.1% 12-Month8.4%7.7% For D+/R- (n=197) Graft Retention at 1-Year 95.6% Graft Retention at 3-Year 91.0% Graft Retention at 5-Year 82.5% Kaplan-Meier survival estimates for Graft Survival