Intravenous Immunoglobulin and Rituximab in HLA Highly Sensitized Kidney Transplant Recipients

Querido, Sara; Weigert, André; Adragão, Teresa; Henriques, Jodélia L. M.; Birne, Rita; Matias, Patrícia; Jorge, Cristina; Nascimento, C.; Bruges, Margarida; Machado, Domingos

doi:10.1016/j.transproceed.2018.02.016

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 51 studies reported the incidence of leukopenia 2 , 8,10–13,16–22,25,27,29,32–35,37,40–42,45,49,50,52–54,56–62,66,67,69,70,72–74,76,77 , 79,80,82,83,86 . The white blood cell (WBC) threshold to define leukopenia varied widely; a threshold WBC ≤3000/μl was most commonly used ( n = 15 studies 2,19,20,27,32,37,40,49,57,62,66,72,74,79,83 ) followed by threshold of ≤3500/μl ( n = 9 studies 10–12,25,41,50,60,80,86 ), ≤4000/μl ( n = 6 studies 33,35,40,42,45,76 ), ≤2000 ( n = 4 studies 11,34,58,73 ), ≤1000/μl ( n = 3 studies 11,42,61 ), ≤5000 ( n = 3 studies 54,70,77 ), ≤1500 ( n = 2 studies 50,60 ), ≤4500/μl ( n = 1 study 53 ); in 15 studies, a threshold definition was not reported 8,13,16–18,21,22,29,52,56,59,61,67,69,82 …”

Section: Resultsmentioning

confidence: 99%

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

Raval

Kistler²,

Tang

et al. 2023

Transplant Infectious Dis

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Raval

Kistler²,

Tang

et al. 2023

Transplant Infectious Dis

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“…The full-text review was undertaken for 886 eligible articles; of these 78 articles discussed HLA incompatibility at the level of the antigen mismatch only, 64-141 whereas 163 articles assessed incompatibility by molecular genotyping, molecular mismatch analysis, and/or pretransplant DSA verification by solid-phase and/or by cell-based assays. 3,142-303 The Preferred Reporting Items for Systematic reviews and Meta-Analyses diagram outlining the article selection process is provided in Figure 1. 304…”

Section: Resultsmentioning

confidence: 99%

Seeking Standardized Definitions for HLA-incompatible Kidney Transplants: A Systematic Review

et al. 2022

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Original Clinical Science-GeneralBackground. There is no standard definition for "HLA incompatible" transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes. Methods. We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility. Results. Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains. Conclusions. Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.

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“…Furthermore, the combination of rituximab with rATG induction therapy in highly sensitized patients (mean class I PRA > 80%) showed superior graft survival at 5 years compared to rATG induction therapy alone (92.9% vs. 48.3%, p = 0.02) [24]. Intravenous immunoglobulin and rituximab combined induction therapy in highly sensitized patients (mean PRA = 62%, ≥3 HLA-mismatch, positive FXM or positive pretransplant DSA) was also effective in graft survival, graft function, and overall patient survival [57]. A study of HLA-incompatible recipients (mean cPRA = 80%, repeat HLA mismatches (80%), CDC positive, FCXM positive, or DSA positive) found that rituximab induction reduced the incidence of HLA-antibody rebound (7% with DSA, 33% non-DSA) compared to those transplanted without rituximab (32% DSA, 55% non-DSA), but demonstrated no effect on DSA elimination, AMR, or year allograft survival [58].…”

Section: Rituximabmentioning

confidence: 89%

Optimal Immunosuppression Strategy in the Sensitized Kidney Transplant Recipient

Olaso

Manook

Moris

et al. 2021

JCM

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Patients with previous sensitization events against anti-human leukocyte antigens (HLA) often have circulating anti-HLA antibodies. Following organ transplantation, sensitized patients have higher rates of antibody-mediated rejection (AMR) compared to those who are non-sensitized. More stringent donor matching is required for these patients, which results in a reduced donor pool and increased time on the waitlist. Current approaches for sensitized patients focus on reducing preformed antibodies that preclude transplantation; however, this type of desensitization does not modulate the primed immune response in sensitized patients. Thus, an optimized maintenance immunosuppressive regimen is necessary for highly sensitized patients, which may be distinct from non-sensitized patients. In this review, we will discuss the currently available therapeutic options for induction, maintenance, and adjuvant immunosuppression for sensitized patients.

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Intravenous Immunoglobulin and Rituximab in HLA Highly Sensitized Kidney Transplant Recipients

Cited by 5 publications

References 21 publications

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

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

Seeking Standardized Definitions for HLA-incompatible Kidney Transplants: A Systematic Review

Optimal Immunosuppression Strategy in the Sensitized Kidney Transplant Recipient

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