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

Abstract

Background Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post‐KT. Methods We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception‐June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs. Results Of 2081 records, 82 studies met inclusion criteria. Seventy‐three studies reported the epidemiology of L/N post‐KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/μl, ranged from 13% to 48% within 1‐year post‐transplant; ANC <500/μl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/μl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post‐KT. D+/R− cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N‐associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti‐thymoglobulin and the need for granulocyte colony‐stimulating factor (G‐CSF) use were common with L/N. Conclusion Findings suggest post‐transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G‐CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post‐KT.

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients

“…Valganciclovir is an inhibitor of CMV DNA polymerase . It commonly causes myelosuppression, especially leukopenia and neutropenia, which can lead to discontinuation/interruption of CMV prophylaxis, dose reduction of immunosuppressants, and/or use of granulocyte colony–stimulating factor(s) (G-CSF) . Valganciclovir requires dose adjustments due to fluctuating kidney function after kidney transplant .…”

“…6,7 It commonly causes myelosuppression, especially leukopenia and neutropenia, which can lead to discontinuation/interruption of CMV prophylaxis, dose reduction of immunosuppressants, and/or use of granulocyte colony-stimulating factor(s) (G-CSF). [6][7][8][9] Valganciclovir requires dose adjustments due to fluctuating kidney function after kidney transplant. 6,10 Additionally, valganciclovir (ganciclovir)-resistant CMV has been detected in individuals with prolonged exposure to or subtherapeutic concentrations of valganciclovir (ganciclovir).…”

Incidence of valganciclovir‐related leukopenia and neutropenia in solid organ transplant recipients at high risk of cytomegalovirus disease

“…12,[16][17][18] Even though leukopenia and neutropenia appear to be common post-SOT, previous studies assessing incidence rates and the impact of leukopenia and/or neutropenia on outcomes have been predominantly in kidney and/or liver transplant recipients. 6,[12][13][14]17,[19][20][21] Importantly, the definitions of leukopenia and/or neutropenia in SOT are variable or missing across the medical literature 6,12,21 which limits comparability between studies.…”

“…6 Granulocyte-colony stimulating factor (G-CSF) is generally safe in SOT 22,23 but it is associated with significant costs. 6 Some studies have suggested no association between leukopenia and neutropenia and/or rates of graft rejection and/or infection 20,21,24 but others have suggested the contrary. 12 A systematic review assessing the burden of leukopenia/neutropenia in adult kidney transplant recipients by Raval and colleagues showed that CMV D+/R-status, mycophenolic acid, and tacrolimus were the most common risk factors for leukopenia/neutropenia.…”

“…Although there was a positive association between leukopenia/neutropenia and acute rejection and opportunistic infections, the results were mixed for graft failure and mortality. 21 A single-center study in heart transplant recipients found CMV D+/R-status, lower baseline leukocytes, and previous CMV infection to be risk factors for post-transplant neutropenia. 25 A recent non-inferiority clinical trial by Limaye and colleagues compared VGCV to letermovir for 200 days in CMV D+/R-kidney transplant recipients.…”