Complement activation plays a key role in the side‐effects of rituximab treatment

Kolk, Lizet E. van der; Grillo-López, Antonio J; Baars, Joke W.; Hack, C. E.; Oers, Marinus H. J. van

doi:10.1046/j.1365-2141.2001.03166.x

Cited by 291 publications

(195 citation statements)

References 16 publications

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“…As already demonstrated in previous papers, 31,32 Rituximab effects rely on complement-and cell-mediated cytotoxicity, which depend on CD55/CD59 levels 33 and on phagocytic activity, respectively. These activities are variable among individuals, and final efficiency on target cells may be different in each patient.…”

Section: Discussionmentioning

confidence: 94%

The conjugate Rituximab/saporin-S6 completely inhibits clonogenic growth of CD20-expressing cells and produces a synergistic toxic effect with Fludarabine

et al. 2004

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Immunotoxins are chimeric proteins consisting of a toxin coupled to an antibody. To date, several clinical trials have been conducted, and some are still ongoing, to evaluate their anti-tumor efficacy. In this view, we chemically constructed an anti-CD20 immunotoxin with the mAb Rituximab and the type 1 ribosome-inactivating protein (RIP) saporin-S6, designed for B cells non-Hodgkin's lymphoma (NHL) therapy. This immunotoxin showed a specific cytotoxicity for the CD20 þ cell lines Raji and D430B, evidenced by inhibition of protein synthesis, evaluation of apoptosis and clonogenic assay. Upon conjugation, saporin-S6 increased its toxicity on target cells by at least 2 logs, with IC 50 values of 0.1-0.3 nM. The percentage of AnnexinV þ cells was over 95% in both cell lines treated with 10 nM immunotoxin. A complete elimination of Raji clones was reached with the 10 nM immunotoxin, whereas a mixture of free RIP and mAb gave about 90% of clonogenic growth. Rituximab/ saporin-S6, at 10 nM concentration, also induced apoptosis in 80% of lymphoma cells from NHL patients. Moreover, sensitivity of Raji to Rituximab/saporin-S6 was augmented when cells were coincubated with Fludarabine. The synergistic toxic effect of the two drugs led to a total elimination of the neoplastic population.

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Section: Discussionmentioning

confidence: 94%

The conjugate Rituximab/saporin-S6 completely inhibits clonogenic growth of CD20-expressing cells and produces a synergistic toxic effect with Fludarabine

et al. 2004

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“…Toxicity and efficacy are related to events after binding, which include B cell signaling, complement activation, direct apoptosis, and antibody dependent cellular cytotoxicity [13]. Complement activation and cytokine secretion, in particular, seems to be the causative factors in side effects associated with infusion reactions [14]. Studies have found complement (C3b/c and C4b/c) and cytokine (TNF-a, IL6, and IL8) levels to be elevated after rituximab infusion [2,[14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…Complement activation and cytokine secretion, in particular, seems to be the causative factors in side effects associated with infusion reactions [14]. Studies have found complement (C3b/c and C4b/c) and cytokine (TNF-a, IL6, and IL8) levels to be elevated after rituximab infusion [2,[14][15][16]. In particular, TNF-a has been postulated as the main component in the pathogenesis of ILD because of its proinflammatory effects by inducing chemokines, inflammatory mediators, and angiogenic factors [17].…”

Section: Discussionmentioning

confidence: 99%

Rituximab‐induced interstitial lung disease

2007

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The aim of this study is to characterize rituximab‐induced interstitial lung disease (R‐ILD). The information on all reported cases of R‐ILD was reviewed. This analysis focused on patient characteristics, underlying disease, rituximab dosing schedule, and R‐ILD characteristic‐like symptoms, diagnosis, treatment, and outcomes. Sixteen cases of R‐ILD, including our two cases, have been reported in the literature. Commonalities include older age, clinical presentation, computerized tomography findings, pulmonary function tests, and biopsy findings. Therapy included corticosteroids and broad spectrum antibiotics. Prognosis has been variable. Patients who worsen despite corticosteroids have a poor outcome. The pathogenesis of R‐ILD is largely unknown. Potential explanations for R‐ILD may include the induction and release of cytotoxic substances. R‐ILD is a rare but potentially fatal pulmonary toxicity due to rituximab. R‐ILD should be considered in patients who present with dyspnea, fever, and cough, and there is no clear evidence of infection. Prompt diagnosis and treatment with corticosteroids is essential. Am. J. Hematol. 82:916–919, 2007. © 2007 Wiley‐Liss, Inc.

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“…Activation of the complement and some inflammatory cytokines (i.e. tumor necrosis factor-alpha) by rituximab may lead to non-specific bystander lysis or inhibition of some stem cells compartments 16,17 . On the other hand, a majority of studies confirm that only CD34+ cell subsets are significantly associated with short-term and long-term hematopoietic reconstitution 18 .…”

Section: Rituximab Does Not Adversely Affect the Stem Cell Mobilizatimentioning

confidence: 99%

Rituximab Does Not Adversely Affect the Stem Cell Mobilization and Engraftment After High-Dose Therapy and Autologous Transplantation in Patients With Diffuse Large B-Cell Lymphoma in First Complete or Partial Remission

Papajík¹,

Pikalova²,

Raida³

et al. 2009

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims and Methods:The goal was to investigate the effect of prior combined rituximab (R) and intensive chemotherapy on peripheral blood stem cell mobilization and their engraftment after stem cell transplantation (ASCT) in 69 patients with poor-risk, diffuse large B-cell lymphoma (DLBCL).Results: A statistically comparable median number of CD34+ stem cells was collected in both groups (13.80x10 6 / kg in the non-R group and 7.81x10 6 /kg in the R group; p = 0.110). A trend toward greater number of CFU-GM was found in the non-R group (98.1x10 4 /kg) compared to the R group (76.6x10 4 /kg; p = 0.068). The non-R patients had a much higher median number of BFU-E (90.9x10 4 /kg) than the R patients (31.3x10 4 /kg; p = 0.001). Conclusions: Hematopoietic engraftment was rapid for both groups and no different between them. The 3-year event-free survival was 90.4 % in the R group and 67.2 % in the non-R group (p = 0.04), but there was no significant difference in the 3-year overall survival (94,7 % vs 83,5 %; p = 0.179).

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Complement activation plays a key role in the side‐effects of rituximab treatment

Cited by 291 publications

References 16 publications

The conjugate Rituximab/saporin-S6 completely inhibits clonogenic growth of CD20-expressing cells and produces a synergistic toxic effect with Fludarabine

The conjugate Rituximab/saporin-S6 completely inhibits clonogenic growth of CD20-expressing cells and produces a synergistic toxic effect with Fludarabine

Rituximab‐induced interstitial lung disease

Rituximab Does Not Adversely Affect the Stem Cell Mobilization and Engraftment After High-Dose Therapy and Autologous Transplantation in Patients With Diffuse Large B-Cell Lymphoma in First Complete or Partial Remission

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