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Abstract

Objectives: Kidney transplant is a new area for use of rituximab, which is being used to treat acute antibodymediated rejection or as an induction agent in ABOor HLA-incompatible grafts. We report on late-onset neutropenia in rituximab-treated kidney transplant recipients with antibody-mediated rejection. Conclusions: Increased use of rituximab to treat antibody-mediated rejection among kidney transplant recipients requires attention to its late-onset adverse event, neutropenia. Although asymptomatic in some patients, kidney transplant recipients treated concomitantly with plasmapheresis and mycophenolate mofetil are predisposed to hypogammaglobulinemia, and monitoring of patients for infections is required.

Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

“…A randomized double-blind, placebo-controlled study of efficacy and safety of rituximab induction in KTR found no thrombocytopenia in rituximab arm [ 42 ]. Likewise in another prospective observational case control study, thrombocytopenia was not seen in KTR receiving rituximab [ 43 ]. However, some noncontrolled studies have reported thrombocytopenia in KTR who received rituximab [ 44 , 45 ].…”

“…LON has frequently been reported in KTR [ 44 , 45 , 56 – 59 ].The frequency of late-onset neutropenia in KTR has been reported from 37.5% to 48% in various studies [ 44 , 45 , 55 , 56 ]. Common medications incriminated in causing LON include mycophenolate mofetil or anti CMV medications (ganciclovir / valganciclovir).Ahmadi F et al [ 43 ] reported a high incidence (66.7%) of late-onset neutropenia [defined as neutropenia that occurred about 4 weeks after the last administered dose of rituximab without any other alternate explanation (e.g., unresponsive to dose reduction/cessation of ganciclovir/ valganciclovir, or mycophenolate mofetil)].…”

Late-Onset Neutropenia after Rituximab Treatment for Adult-Onset Nephrotic Syndrome

“…R-LON is frequently reported in patients with B-cell lymphoma but has also been reported in cases of rheumatoid arthritis, systemic lupus erythematosus [9], overlap syndrome [8], renal transplantation [5, 7] and antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis [6]. The incidence is 3%-27% in B-cell lymphoma [11], 1.3%-2.3% in rheumatoid arthritis and autoimmune diseases [9], and 42%-70% in autologous stem cell transplantation [7]. The wide range of incidences is attributable to the diversity in patient backgrounds and treatments, inconsistent definitions of R-LON in the literature, and differences in the frequency of post-RTX administration blood sampling.…”

“…Although R-LON is generally asymptomatic and is known to spontaneously go into remission, reported cases of complicating infection that requires G-CSF or antibiotic treatment also exist [5, 6, 9–11, 13]. Deaths have also occurred due to severe infection [7, 19]. Caution is thus required to prevent R-LON onset.…”

State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies

“…Outside the context of oncology, biotherapies have been reported as being the cause of early and transient Grade 1–2 neutropenia in 10–15% of the treated patients, often with TNF-α inhibitors [16,19,20,21,22,23,24], tocilizumab [25,26,27], rituximab [14,27,28,29,30,31,32,33,34,35,36], and alemtuzumab [15,37,38,39,40,41,42]. In a retrospective cohort study involving 499 patients with rheumatic diseases (rheumatoid arthritis in 72% of the diseases) treated by intravenous abatacept, infliximab, or tocilizumab, Espinoza et al report at least one neutropenic episode in 52 patients (10.4%) [26].…”