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

Transpl Infect Dis. 2023 Feb;25(1):e14000 doi: 10.1111/tid.14000.

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.


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.


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.


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.

CET Conclusion
Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: There are some good indicators of best-practice in the process of this systematic review, such as reference to the PRISMA guidelines and searching multiple databases. In addition, conference abstracts were searched to identify further possibly relevant information. However a single author screened abstracts and subsequently full texts for inclusion. Data was extracted by a sole author and validated by another, rather than being extracted in duplicate and then resolved. These are potential sources of bias or error. A formal assessment of study quality was completed, but only by one author. A large number of studies were included (82), with a total patient population of 41,705. Unfortunately, there was a wide variation in the white blood cell and neutrophil thresholds to define leukopenia and neutropenia. WBC<3000/microlitre was most commonly used for leukopenia (15 studies) and neutrophils<1000/microlitre was most commonly used for neutropenia (12 studies). The authors then divide the results by immune induction regimen and length of follow up, which produces a range of rates for leukopenia and neutropenia that is reliant on single studies in many incidences. Whilst this systematic review provides an overview, if a more specific research question had been set at the outset then more firm conclusions could have been drawn.
Study Details
Aims: The aim of this study was to summarise the available evidence regarding the incidence, risk factors and clinical and economic outcomes of leukopenia and neutropenia (L/N) following kidney transplantation.
Interventions: Electronic databases including MEDLINE, Embase, and the Cochrane Library, as well as conference proceedings were searched. Studies were selected for inclusion and data were extracted by a single researcher. The methodological quality of the included studies was assessed using the Newcastle-Ottawa tool for non-randomised studies, Motheral et al checklist for retrospective and registry studies, and the Joanna Briggs Institute Critical Appraisal Checklist for analytical cross-sectional studies.
Participants: 82 studies were included in the review.
Outcomes: Incidence or prevalence of leukopenia/neutropenia, the adjusted risk factors for leukopenia/neutropenia, the association between leukopenia/neutropenia occurring posttransplantation, infection, allograft rejection, graft loss, and mortality, healthcare resource utilization and healthcare costs.
Follow Up: N/A
Funding: Industry funding
Publication type: Systematic Review
Organ: Kidney
Language: English
Author email:
MeSH terms: Humans; Adult; Kidney Transplantation; Neutropenia; Leukopenia; Valganciclovir; Immunosuppressive Agents; Granulocyte Colony-Stimulating Factor; Mycophenolic Acid; Anemia; Opportunistic Infections; Transplant Recipients; Graft Rejection; Granulocyte Colony Stimulating Factor; Gcu97 Fkn3 R (Valganciclovir); 0 (Immunosuppressive Agents); 143011 72 7 (Granulocyte Colony Stimulating Factor); Hu9 Dx48 N0 T (Mycophenolic Acid)