A split strategy to prevent cytomegalovirus after kidney transplantation using prophylaxis in serological high‐risk patients and a pre‐emptive strategy in intermediate‐risk patients: Combining the best of two options?

Abstract

Background Cytomegalovirus (CMV) remains an important challenge after kidney transplantation. Current Transplantation Society International Consensus Guidelines recommend antiviral prophylaxis or pre‐emptive therapy for high‐risk CMV‐seronegative recipients with a CMV‐seropositive donor (D+/R−) and moderate‐risk CMV‐seropositive recipients (R+). However, a split strategy according to CMV serostatus is not specifically mentioned. Methods We evaluated a split strategy to prevent CMV infection after kidney transplantation in which D+/R− patients received valganciclovir (VGC) prophylaxis for 200 days, and R + patients were treated pre‐emptively according to CMV DNAemia. Patients were followed until 1‐year post‐transplant. Results Between April 2014 and March 2018, 40 D+/R− and 92 R + patients underwent kidney transplantation. Forty‐six percent received antithymocyte globulin (ATG) induction, and 98% was treated with calcineurin inhibitors, mycophenolic acid (MPA), and steroids. No D+/R− patient developed CMV disease during prophylaxis (median 200 days), but 15% developed post‐prophylaxis or late‐onset disease. Fifty‐three percent developed neutropenia during prophylaxis, including 16/40 (40%) grade 3 or 4 neutropenia requiring reduction/discontinuation of MPA (30%) and/or VGC (35%), and an occasional need for granulocyte colony‐stimulating factor (5%). In the R + group, 40% received antiviral therapy for a median duration of 21 days; 5% developed early‐onset CMV disease. Only 5% developed neutropenia. D+/R + status (hazard ratio (HR) 2.09,P = .004) and ATG use (HR 2.81, P < .0001) were risk factors for CMV reactivation. Conclusions Prophylaxis leads to acceptable CMV control in high‐risk patients but comes with a high risk of neutropenia. Pre‐emptive therapy is effective and limits drug exposure in those at lower risk of CMV.

Decreased incidence of acute rejection without increased incidence of cytomegalovirus (CMV) infection in kidney transplant recipients receiving rabbit anti‐thymocyte globulin without CMV prophylaxis – a cohort single‐center study

“…A recent study showed that among 40 D+/R− kidney transplant recipients receiving pharmacological prophylaxis for 200 days, the incidence of neutropenia was 53%, 30% had to reduce/discontinue MPA and 35% valganciclovir, with still 15% late CMV infection. In the same study, among 92 R+ patients receiving preemptive therapy, 40% were treated for CMV, with a mean duration of 21 days, and only 5% developed neutropenia [32]. A recent multicenter, open‐label, randomized clinical study showed that the incidence of CMV infection or disease was 11.5% among patients receiving prophylaxis and 39.7% in those receiving preemptive therapy.…”

Burden of neutropenia and leukopenia among adult kidney transplant recipients: A systematic literature review of observational studies

“…Subsequently, a total of 75 papers were excluded during either full‐text screening or data extraction. Ultimately, 82 citations 2,6–86 including 65,386 participants met inclusion criteria.…”

“…A total of 27 studies reported neutropenia incidence 2 , 6,11,14,15,26,30,31,34,36,39,42,44,46–48,51,60,63,64,68,69,75,76,78,81,85 . The absolute neutrophil count (ANC) threshold to define neutropenia varied widely; the majority of the studies ( n = 12) reported neutropenia with a threshold of ANC <1000/μl 2,6,11,15,26,36,44,51,63,75,81,85 followed by a threshold of <500/μl ( n = 8 11,26,34,42,44,60,81,85 ), <1500/μl ( n = 7 26,44,46,60,68,76,81 ), and <2000/μl ( n = 3 64,78,81 ); in 7 studies 14,30,39,42,47,48,69 , a threshold definition was not reported. In 1 study, 31 neutropenia was defined using an International Classification of Diseases, Ninth Revision (ICD‐9) code.…”

A Systematic Review and Meta-analysis of Optimized CMV Preemptive Therapy and Antiviral Prophylaxis for CMV Disease Prevention in CMV High-Risk (D+R-) Kidney Transplant Recipients

“…Among 877 studies screened, 154 duplicates and 586 studies were excluded from the title/abstract, leaving 137 studies that included 149 cohorts (115 UP and 34 PET) that were fully reviewed for eligibility by 2 independent authors (Figure 1). Among these 137 studies, 19 UP studies 13,27,[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] and 6 PET studies [19][20][21][52][53][54] met inclusion criteria, comprising 993 patients in the UP cohort and 234 patients in the PET cohort. One study that met inclusion criteria was excluded because of variable definitions of CMV disease and overlap of cohorts from the same center in 2 separate publications.…”