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Through narrative, the subjective experience of illness offers a corrective to biomedicine's interpretive grip. Narrative is both process and product and illness narratives, in particular, are examples of embodied research. This ecopathography – drawing upon embodied experiences of treatment and recovery from late stage Non-Hodgkin's lymphoma – enlists Haraway's cyborg and Lupton's digital assemblage in an effort to make broader claims about patient care in the United States, and specifically, the role of technology in healthcare and in the construction of patient identity. A surgically implanted port (facilitating blood draws and the delivery of chemotherapy) and the patient portal (representing the results of those blood draws as well as a medium for communication) provide a foundation for how cyborgian assemblages both assist and trouble the cancer experience. At stake is the fluidity and ambiguity of boundaries (human/machine, human/animal, and physical/virtual) and the management of those boundaries with regard to patient care. [ABSTRACT FROM AUTHOR]

Chemotherapy, including bendamustine, usually causes lymphocytopaenia and hypogammaglobulinaemia as side effects in patients with haematological malignancies. Therefore, the possibility has been considered that these immunological adverse events induced by bendamustine may lead to infectious diseases. However, lymphocytopaenia and/or hypogammaglobulinaemia have not yet been shown to have a statistically significant association with infection in cancer patients who receive bendamustine. We retrospectively studied 27 patients with relapsed or refractory indolent follicular lymphoma who were treated with bendamustine and rituximab (BR). In order to elucidate relationships between immune-related laboratory parameters (i.e. peripheral blood leukocyte, neutrophil, lymphocyte and immunoglobulin G [IgG]) and infectious events, receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. Infectious diseases occurred in 11 patients (11/27, 41%), including 3 (3/27, 11%) with severe diseases. The area under the ROC curve (AUC) showed that the lowest IgG level during and after BR discriminated infectious events (cut-off value, 603 mg/dL) with 81.8% sensitivity and 68.8% specificity (AUC, 0.76; 95% CI, 0.52-0.90). Furthermore, a multivariate regression analysis revealed that the minimal serum IgG value during and after BR therapy was the only variable that was significantly associated with infection (odds ratio, 8.29; 95% CI, 1.19-57.62; p value, 0.03). Serum IgG ≤603 mg/dL during and after BR therapy was independently associated with an increased risk of infection. The monitoring of serum IgG during chemotherapy may help to predict the development of infection in blood cancer patients undergoing chemotherapy with bendamustine in combination with rituximab. [ABSTRACT FROM AUTHOR]

We report efficacy, safety and biomarker data from a phase-II study evaluating atezolizumab (eight 21-day cycle as induction therapy) in combination with obinutuzumab in patients with relapsed/refractory mantle cell lymphoma (MCL, n = 30) or Waldenström's macroglobulinemia (WM, n = 4), and in combination with rituximab in patients with marginal zone lymphoma (MZL, n = 21). All patients received atezolizumab monotherapy as maintenance for ≤10 cycles. Objective response rates at end of induction were 16.7% (MCL) and 42.9% (MZL), with no responses in WM. Median duration of response was 6.8 months (range 5.7–not estimable) for MCL and not reached for MZL. Treatment-emergent adverse events (TEAEs) occurred in 93.3%, 95.2% and 100% of MCL, MZL and WM patients, respectively. One fatal TEAE (pneumonia) occurred in each of the MCL and MZL groups. Biomarker analysis highlighted the importance of characterizing the immune environment to optimize efficacy of immunotherapy regimens. Trial registration details: EudraCT: 2016-003579-22 [ABSTRACT FROM AUTHOR]

Immunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who were all treated with convalescent plasma (CCP) along with standard treatment. We performed an observational, retrospective case series between May 2020 to March 2021 at three sites in Skåne, Sweden, with a population of nearly 1.4 million people. All patients hospitalized for COVID-19 who received CCP with the indication severe immunosuppression as defined by the treating physician were included in the study (n = 28). In total, 28 severely immunocompromised patients, half of which previously had been treated with rituximab, who had received in-hospital convalescent plasma treatment of COVID-19 were identified. One week after CCP treatment, 13 of 28 (46%) patients had improved clinically defined as a decrease of at least one point at the WHO-scale. Three patients had increased score points of whom two had died. For 12 patients, the WHO-scale was unchanged. As one of only few studies on CCP treatment of COVID-19 in hospitalized patients with severe immunosuppression, this study adds descriptive data. The study design prohibits conclusions on safety and efficacy, and the results should be interpreted with caution. Prospective, randomized trials are needed to investigate this further. [ABSTRACT FROM AUTHOR]

Although treatment with anti-CD20 monoclonal antibodies (mAb) has improved outcomes in B-cell malignancies, it's associated with increased risk of hypogammaglobulinemia (HG). Our study aimed to determine the effects of anti-CD20 mAb on serum immunoglobulins (Ig) in follicular lymphoma (FL). Ig concentrations, infectious complications, and need for intravenous Ig were evaluated by level of exposure to anti-CD20 mAb in 380 patients. Prevalence of HG significantly differed by level of treatment exposure (p < 0.001). Single course anti-CD20 mAb was associated with rising IgG (+10.3 mg/dL/year), whereas the addition of maintenance therapy (−7.4 mg/dL/year) or multiple courses of treatment (−10.3 mg/dL/year) was associated with declining IgG. Among patients treated with anti-CD20 mAb, 45.2% developed IgG-HG and 10.3% developed symptomatic IgG-HG. Pretreatment IgG levels gradually declined in all patients, suggesting tumor burden may contribute to HG. Baseline and periodic monitoring of serum Ig is appropriate in patients with FL, including those managed with active surveillance. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) reactivation is a well-known complication after rituximab-based chemotherapy in patients with B cell lymphoma (BCL) who have resolved HBV infection. This retrospective cohort study used electronic medical records from the Kaohsiung Chang Gung Memorial Hospital. There were 128 patients with BCL and resolved HBV infection treated with 1st-line rituximab-containing therapy from 2008 to 2013. No patient received antiviral prophylaxis. Patients with high pretreatment hepatitis B surface antibody (anti-HBs titer ≥100 mIU/mL), had significantly less HBV reactivation (2.0%, 1/49) than patients with low (10–100 mIU/mL, 10.8%, 4/37) or negative anti-HBs (<10 mIU/mL, 23.8%, 10/42) (p = 0.001). No patient in the high group vs. 1 (2.7%) low group vs. 6 (14.3%) negative group developed HBV-related hepatitis (p = 0.002). Patients with high pretreatment anti-HBs have a low risk of HBV-related complications and may not require antiviral prophylaxis. We propose an algorithm for the management of HBV reactivation risk in BCL. [ABSTRACT FROM AUTHOR]

Purpose: To describe a case of retinal occlusive vasculopathy associated with intravitreal administration of rituximab.Methods: A single case report from a tertiary referral center.Results: The patient described in the following case report developed a diffuse retinal occlusive vasculopathy following intravitreal rituximab for intraocular lymphoma. He required panretinal photocoagulation, avastin, and cyclophotocoagulation to control his intraocular pressure from ocular ischemia resulting in neovascular glaucoma.Conclusions: This is the first reported case of occlusive retinal vasculopathy subsequent to intravitreal administration of rituximab. Whereas hypersensitivity reactions to intravenous infusion of rituximab have been noted in the literature, no such reports exist in response to intravitreal therapy. [ABSTRACT FROM AUTHOR]

Activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) is associated with worse survival after standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) chemoimmunotherapy compared to germinal center B-cell-like (GCB) subtype. Preliminary evidence suggests that benefits from novel agents may vary by subtype. Hypothesizing that treatment stratified by DLBCL subtype could be potentially cost-effective, we developed micro-simulation models to compare three first-line treatment strategies: (1) standard RCHOP for all patients (2) subtype testing followed by RCHOP for GCB and novel treatment for ABC DLBCL, and (3) novel treatment for all patients. Based on phase 2 evidence, we used lenalidomide + RCHOP as a surrogate novel treatment. The subtype-based approach showed a favorable incremental cost-effectiveness ratio of $15,015/quality-adjusted life year compared with RCHOP. Although our exploratory analyses demonstrated a wide range of conditions where subtype-based treatment remained cost-effective, data from phase 3 trials are needed to validate our models’ findings and draw definitive conclusions. [ABSTRACT FROM AUTHOR]

In 120 Stage I–IV testicular diffuse large B-cell lymphoma (DLBCL) patients treated from 1964 to 2015, we assessed the benefits of prophylactic contralateral testicular radiation (RT) and prophylactic central nervous system (CNS) therapy on overall, progression free, testicular relapse free, and CNS relapse free survival (OS, PFS, TRFS, and CRFS, respectively). Seventy percent of patients received RT, 53% received anthracyclines and rituximab (modern therapy), and 61% received CNS prophylaxis. On univariate analysis RT was associated with improved TRFS, PFS, and trended toward improved OS. On multivariate analysis (MVA), RT was significantly associated with improved OS and PFS; the PFS benefit persisted among patients receiving modern therapy. CNS prophylaxis was associated with improved OS, PFS, and TRFS, but not CRFS on univariate analysis, and was not significant on MVA. RT is associated with improved survival, and should be considered for all testicular DLBCL patients, but additional strategies are needed to prevent CNS relapse. [ABSTRACT FROM AUTHOR]

Rituximab is an effective treatment for CD20+B-cell malignancies and autoimmune disorders. However, adverse drug reactions (ADRs) may occur after rituximab infusion, causing, in rare cases, its discontinuation. In this multicenter, retrospective study, among 374 patients treated with rituximab i.v., 23.5% experienced ADRs. Mean follow-up was 20.6 months (range 8–135). Overall, ADRs were significantly more frequent in non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (25–35.9%), than in autoimmune diseases (9.4–17.5%) (p<.0001). Grade 3–4 toxicity was observed in eight patients (2.1%), and in four of them (1% of all patients) definitive drug discontinuation was necessary. Interestingly, three groups of patients with different risk of developing ADR were identified, according to a predictive heat-map developed combining four parameters (splenomegaly, history of allergy, hemoglobin levels and gender) selected by multivariate analysis. This model may be useful in identifying patients at higher risk of ADRs, needing appropriate preventing therapies. [ABSTRACT FROM AUTHOR]

Rituximab (R) is an anti-CD20 monoclonal antibody which has become an essential component for the treatment of B-cell lymphomas. When associated to chemotherapy it improves the outcome of the patients with diffuse large B-cell lymphoma, follicular lymphoma, and other lymphoproliferative diseases in comparison to chemotherapy alone. For patients with newly diagnosed follicular lymphoma achieving at least a partial response to initial immuno-chemotherapy, maintenance R was associated with an improvement in progression-free survival and a meta-analysis of randomized maintenance trials suggests an overall survival advantage. The role of maintenance R in other indolent diseases is less well-defined. In this article, we summarize the data available for this strategy in less frequent subtypes of indolent B-cell lymphomas. [ABSTRACT FROM AUTHOR]

Moderate, but not massive intensification of CHOP-21 improves outcome in aggressive non-Hodgkin lymphoma. Adding immunotherapy with Rituximab was a break-through, but levels differences in chemotherapy. Ongoing trials attempt to optimize R-CHOP type regimens. We present a mathematical model of chemo-immunotherapy to explain published and aiming at predicting future trials comparing R-CHOP variants. We hypothesize that, for cure, the immune system must dominate residual tumor cells at the end of treatment. Chemotherapy reduces both tumor and immune cells. Rituximab immunotherapy boosts the immune response. We translate this reasoning into a differential equations model. Model parameters are estimated using data of randomized clinical trials in elderly patients. The model explains observed hazard ratios between treatments. It explains why too intense chemotherapy could be detrimental. The model is validated predicting six published independent studies. As an application, we varied treatment schedules and predict that current R-CHOP variants have only limited optimization potential. [ABSTRACT FROM AUTHOR]

Maintaining high relative dose intensity (RDI) is associated with improved outcomes, especially in patients with aggressive B-cell non-Hodgkin lymphoma (NHL). To evaluate changes in practice, we examined RDI, chemotherapy treatment patterns, dose delays and reductions, neutropenia and related consequences, and supportive care in 500 patients with aggressive B-cell NHL treated between 2006–2009. We then compared the results to a previous study of patients treated between 1993–2001. Relative to the previous study, rituximab was a common addition to CHOP-21 (91% vs. 3%), more patients received an RDI ≥ 85% (68% vs. 52%), and fewer patients experienced dose reductions (21% vs. 35%), though incidences of dose delays were similar (26% vs. 23%). Incidences of febrile neutropenia (FN; 12% vs. 21%) and FN-related hospitalizations (10% vs. 16%) were lower. Finally, more patients received primary prophylaxis with colony-stimulating factors (75% vs. 12%). Together, these results illustrate evolving practice patterns for patients with aggressive B-cell NHL. [ABSTRACT FROM PUBLISHER]

Purpose: To evaluate the efficacy of systemic rituximab immunotherapy in the management of primary ocular adnexal lymphomas (OAL). Materials and methods: Clinical records of 10 consecutive patients (11 eyes) with biopsy-proven OAL managed with systemic anti-CD20 monoclonal antibody (rituximab; 375 mg/m2 intravenously once every three weeks for 6-8 cycles) between June 2008-March 2013 were evaluated retrospectively. Orbital magnetic resonance imaging and positron emission tomography were performed to evaluate any orbital and systemic involvement, respectively. Clinical response was classified as complete or partial. Results: The age of patients ranged between 27-85 (median, 55) years. Nine patients (90%) presented with unilateral and one (10%) with bilateral conjunctival involvement. Orbit was affected in 4 patients (40%), one of which had also choroidal involvement (10%). None of the patients had systemic involvement at initial presentation. All patients received an average of 7 cycles (range, 6-8) of systemic immunotherapy. After a median follow-up of 31 months (range, 10-61 months), complete response without recurrence could be achieved in 4 eyes (36%) with rituximab monotherapy. No systemic or ocular side effects were observed in any patient. Additional radiotherapy was required in 6 patients (7 eyes; 64%) with partial response or recurrence. Conclusions: Complete regression of primary OALs without recurrence was observed in about one-third of eyes after systemic rituximab monotherapy. Adjunctive radiotherapy was required in remaining two-thirds of the cases to achieve complete response. Thus, considering the balance between high rate of local control and potential ocular complications of radiotherapy, systemic rituximab can be considered as a first-line therapeutic option in the management of primary OAL. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) reactivation is a serious but preventable complication for patients with lymphoma receiving systemic therapy. Without antiviral prophylaxis, the HBV reactivation rate is estimated to be > 50% in patients who are positive for hepatitis B surface antigen (HBsAg), and fatal hepatic failure is not uncommon. Current guidelines suggest that routine antiviral prophylaxis should be administered to all HBsAg-positive patients until 6-12 months after completion of chemotherapy. For those who are negative for HBsAg and positive for hepatitis B core antibody, HBV reactivation is uncommon when a conventional dose of chemotherapy is administered. However, with rituximab-containing immunochemotherapy, the HBV reactivation rate is 18% and the clinical course can vary from asymptomatic viremia to fulminant hepatic failure that can be potentially fatal. In this review, we discuss the risk, clinical course and prophylactic strategy of HBV reactivation in patients with lymphoma treated with chemotherapy with or without rituximab. [ABSTRACT FROM AUTHOR]

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is difficult to treat, with limited therapeutic options. Review of prognostic indices, DLBCL genetic classification, previous rituximab exposure, interval from previous therapy, chemosensitivity to salvage therapy and response on imaging is helpful when deciding upon appropriate candidates for further therapy. For appropriately selected patients, the primary strategy is to obtain remission with salvage therapy and proceed to autologous stem cell transplant (ASCT). However, salvage therapy and transplant conditioning regimens are suboptimal, as are therapeutic options for patients who relapse following ASCT. Recent research highlights the ongoing difficulty in the treatment of relapsed/refractory DLBCL, and novel treatments are needed. [ABSTRACT FROM AUTHOR]

To assess the effects of chemoimmunotherapy on post-chemotherapy cognitive impairments (PCCI) in patients with B-cell non-Hodgkin lymphoma (NHL), we used objective and subjective measures of cognitive functions in combination with serum parameters and neuroelectric recordings. Self-perceived status of cognition, fatigue and emotional functioning were reduced in patients ( n = 30) compared to healthy controls ( n = 10). Cognitive performance was impaired in patients with NHL compared to controls and a norm sample ( n = 1179). PCCI was more severe in patients treated with rituximab and bendamustine (BR) than in patients who received R in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) polychemotherapy (R-CHOP). Individual alpha peak frequency and serum brain-derived neurotrophic factor (BDNF) levels in patients with NHL correlated with accuracy in the objective cognition test. Higher serum interleukin-6 (IL-6) concentrations were associated with higher fatigue levels. Patients with NHL and especially those who were treated with BR were affected by PCCI. BDNF and IL-6 might be involved in the pathogenesis of PCCI and fatigue. [ABSTRACT FROM AUTHOR]

APO866 is an inhibitor of nicotinamide adenine dinucleotide (NAD) biosynthesis that exhibits potent anti-lymphoma activity. Rituximab (RTX), an anti-CD20 antibody, kills lymphoma cells by direct apoptosis and antibody- and complement-dependent cell-mediated cytotoxicities, and has clinical efficacy in non-Hodgkin cell lymphomas. In the present study, we evaluated whether RTX could potentiate APO866-induced human B-lymphoma cell death and shed light on death-mediated mechanisms associated with this drug combination. We found that RTX significantly increases APO866-induced death in lymphoma cells from patients and lines. Mechanisms include enhancement of autophagy-mediated cell death, activation of caspase 3 and exacerbation of mitochondrial depolarization, but not increase of reactive oxygen species (ROS) production, when compared with those induced by each drug alone. In vivo, combined administration of APO866 with RTX in a laboratory model of human aggressive lymphoma significantly decreased tumor burden and prolonged survival over single-agent treatment. Our study demonstrates that the combination of RTX and APO866 optimizes B-cell lymphoma apoptosis and therapeutic efficacy over both compounds administered separately. [ABSTRACT FROM AUTHOR]

The use of rituximab has significantly improved outcomes in patients with haematological malignancies and autoimmune disease. There are reports of rituximab-associated ulcerative colitis; however, we report for the first time, two cases of rituximab-induced Crohn’s disease in elderly patients treated for lymphoma. Both patients had evidence of inflammation, ulceration, and granulomas consistent with Crohn’s disease, and responded well to immunosuppression. The association of rituximab and ileocolitis suggests a protective effect of CD20 + lymphocytes in the gut, and implicates their depletion to the development and exacerbation of inflammatory bowel disease. [ABSTRACT FROM PUBLISHER]

This study analyzed the prognostic significance of soluble interleukin-2 receptor α (sIL-2Rα) levels in 100 prospectively enrolled patients with previously untreated follicular lymphoma. It showed that sIL-2Rα level ≥ 115 pmol/L at the time of treatment initiation correlated with a high Follicular Lymphoma International Prognostic Index-2 (FLIPI-2), bulky disease, advanced clinical stage, number of involved lymph nodes, bone marrow involvement and elevated β2-microglobulin (B2M) level. When testing all patients, sIL-2Rα ≥ 115 pmol/L was associated with significantly shorter progression-free (PFS; p < 0.03, hazard ratio [HR] 2.04) but not overall (OS; p = 0.06, HR 2.36) survival rates. Subanalysis of patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) ± rituximab showed higher predictive power for both PFS (HR 2.75, 95% confidence interval [CI] 1.24-6.11, p = 0.01) and OS (HR 3.33, 95% CI 1.15-9.63, p = 0.02). In the whole population ( n = 100), only B2M proved a significant univariate predictor ( p = 0.007, HR = 2.8) of PFS. When testing patients treated with CHOP ± rituximab, sIL-2Rα was found to be the best univariate predictor for PFS among all FLIPI-2 factors (HR = 2.68, p = 0.015). Serum IL-2Rα levels may help to refine risk assessment in the modern immunotherapy era complementary to FLIPI-2 factors. [ABSTRACT FROM AUTHOR]

We conducted a systematic review of grade 3/4 adverse events (AEs) reported in prospective trials enrolling patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) receiving maintenance rituximab (MR). Random-effects models were used to calculate summary estimates and 95% confidence intervals for the proportion of AEs occurring during MR. Differences by induction program, histology, setting and MR schedule were examined by stratified analyses and univariate random-effects meta-regression. Eleven trials met the search criteria, with nine sufficiently reporting AEs during the MR phase. Of 1009 patients receiving MR, the proportion experiencing cumulative grade 3/4 toxicity was 24% (95% confidence interval [CI]: 14-36%). Patients receiving MR every 6 months as four weekly infusions for 2 years had significantly less toxicity compared with those receiving MR every 2 months (10% vs. 28%; p = 0.035). Patients treated with rituximab alone during induction had fewer toxicities compared to those treated with rituximab plus chemotherapy induction (12% vs. 35%; p = 0.031). Myelosuppression and infections were the most common toxicities. Our literature analysis suggests that MR given every 6 months and rituximab alone as induction may be associated with fewer grade 3/4 AEs for patients with FL and MCL; however, assessing the true independent impact of induction regimens and schedule on toxicity will require prospective trials. [ABSTRACT FROM AUTHOR]

In this retrospective cohort study of 174 consecutive, newly diagnosed cases of diffuse large B-cell lymphoma (DLBCL), clinical and pathological variables, treatment, response and survival were compared for patients aged 80 and over ( n = 40) to those under 80. Eastern Cooperative Oncology Group (ECOG) status and International Prognostic Index (IPI) were significantly worse among older patients. Standard treatment was given to only 32.5% of older versus 86.6% of younger patients, and 65% of the elderly did not receive standard therapy. At 12 months, overall and event-free survival were 51.3% (95% confidence interval [CI]: 35-66%) vs. 93% (CI: 88-97%) and 41.9% (CI: 25-58%) vs. 84.8% (CI: 77-90%), for older versus younger patients, respectively. Choice of therapy was significantly associated with survival in the elderly, and low albumin but not comorbidity score was associated with not receiving standard therapy. Patients with DLBCL aged 80 and over are distinct from all other age groups with regard to treatment tolerance. A minority can receive standard therapy, but for the majority, novel therapeutic options are needed. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the clinical characteristics, treatment results, and analyze the prognostic factors among patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). We retrospectively reviewed 98 patients with MALT lymphoma consecutively diagnosed at the Cancer Institute Hospital. Eighty-one patients (82%) had localized disease and 17 patients (17%) had advanced disease. The primary site was gastric in 52, and extra-gastric in 46. With a median follow-up of 40 months, the estimated 3-year overall survival (OS) and progression free survival (PFS) of the entire group were 100% and 89%, respectively. Three-year PFS was significantly better in patients with gastric lymphoma than in those with non-gastric lymphoma (95% vs. 82%, p = 0.043). Patients with localized disease had significantly better 3-year PFS than those with advanced disease (94% vs. 73%, p = 0.026). Upon multivariate analysis, non-gastric lymphoma retained prognostic significance for PFS. [ABSTRACT FROM AUTHOR]

This is a randomized trial evaluating the safety and immunogenicity of one or two doses of 2009 pandemic H1N1 influenza vaccination in adults with lymphoid malignancies. Adults with a lymphoid malignancy receiving active systemic therapy, or within a year after autologous stem cell transplant, received one dose of AS03-adjuvanted A/California/7/2009 (H1N1) vaccine, and were randomized 21 days later to a second dose or no further vaccination. The primary outcomes were seroprotection and seroconversion rates by hemagglutination inhibition 21 and 42 days after initial vaccination. Twenty-two patients received one dose, and 20 patients received a second dose. Seroconversion rates at day 21 were 30% (one dose) and 5% (two doses), and subsequently 30% for both groups at day 42. Seroprotection rates at day 21 were 40% (one dose) and 15% (two doses), and subsequently 35% (one dose) and 40% (two doses) at day 42. Differences in serologic endpoints were not statistically significant between both study arms at day 42. Patients with low levels of B-cells (CD19-positive) had low seroconversion rates on days 21 (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.59-0.93, p = 0.043) and 42 (OR 0.12, 95% CI 0.01-1.07, p = 0.058). Only three of the 14 patients who received rituximab achieved seroprotective titers by day 42. Patients with lymphoid malignancies did not achieve rates of seroconversion or seroprotection seen in healthy subjects despite a second dose and the use of an adjuvant. Notwithstanding suboptimal immunogenicity, seasonal and pandemic influenza vaccination should continue to be recommended. [ABSTRACT FROM AUTHOR]

We evaluated hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression and their prognostic significance in diffuse large B-cell lymphoma (DLBCL). Expression of HIF-1α and VEGF was studied in 78 patients and results correlated with clinicopathological and prognostic data. HIF-1α and VEGF were expressed in 67% and 84% of patients, respectively, and a significant correlation was demonstrated between them ( p < 0.001). Outcome was analyzed according to treatment. HIF-1α positive patients given rituximab demonstrated improved outcome, with 5-year overall survival of 72% for those receiving rituximab versus 65% for those not receiving rituximab, and 5-year progression-free survival (PFS) 76% versus 57%. No correlation was demonstrated between HIF-1α and other prognostic biomarkers including BCL6, CD10 and MUM-1. We demonstrated significantly improved PFS ( p = 0.003) in patients receiving rituximab and showing BCL6 overexpression. The results confirm the significant association between HIF-1α and VEGF expression and suggest that HIF-1α expression is a favorable prognostic factor in patients with DLBCL treated with rituximab. [ABSTRACT FROM AUTHOR]

Late-onset neutropenia (LON) following rituximab therapy is a recently recognized adverse effect occurring in various clinical settings. However, the true incidence and pathogenesis of this adverse effect are not fully understood. We retrospectively reviewed the medical records of 160 patients with diffuse large B-cell lymphoma (DLBCL) in complete remission (CR) following first-line treatment with rituximab-containing therapy. The incidence of LON was 26.9% (grade 1, 2, 3 and 4) and the incidence of severe LON (grade 3 and 4) was 7.5%. The risk factors for the occurrence of LON were not identified, and overall survival did not differ between patients who developed LON and those who did not. This study suggests that LON is a quite common complication to rituximab therapy. However, more studies are needed in order to elucidate the true mechanism behind and risk factors for LON. [ABSTRACT FROM AUTHOR]

Patients with relapsed or refractory diffuse large B-cell lymphoma may experience extended survival with second-line chemotherapy and autologous stem cell transplant (ASCT). Since a major determinant of outcome after ASCT is responsiveness to second-line therapy, the development of more effective second-line treatments is desirable. We investigated the addition of bortezomib to rituximab, dexamethasone, ifosfamide, cisplatin and etoposide (VIPER). Fifteen patients were enrolled, of whom seven were refractory to first-line chemotherapy and only three had maintained first response for 1 year. Nine (60%) patients achieved objective responses, of which three (20%) were IWC-PET (International Workshop Criteria positron emission tomography) complete responses. Median progression-free survival was 3 months, and median overall survival was 10 months. At a median follow-up of 26 months, five patients (33%) remained alive. Treatment was well tolerated with no unexpected toxicity. Although response rates did not meet predefined criteria, activity was at least comparable to other second-line approaches despite a poor-prognosis patient population. [ABSTRACT FROM AUTHOR]

Rituximab (R) has changed the prognosis of patients with non-Hodgkin's lymphoma (NHL) in developed countries, but its role has not been analyzed in underprivileged circumstances. One hundred and two patients with NHL treated in a developing country were analyzed: 28 patients with follicular lymphoma (FL) and 74 with diffuse large B-cell lymphoma (DLCL). Patients were treated upfront with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or R-CHOP; the decision to employ R depending solely on the ability of patients to defray it. In DLCL, 42 were given CHOP and 32 R-CHOP, whereas in FL, 19 were given CHOP and 9 R-CHOP. The impact of the addition of R was found to be clearer in FL than in DLCL. In patients with DLCL, the overall survival (OS) was 87% at 80 months for those treated with R-CHOP and 84% at 145 months for those treated with CHOP (not significant). In patients with FL, the OS was 89% at 88 months for those treated with R-CHOP and 71% at 92 months for those treated with CHOP (P = 0··05). In a multivariate analysis, other variables which were identified to be associated with the OS were IPI and number of cycles in DLCL. It is concluded that R produced a mild positive impact in the OS of patients with FL, but not in those with DLCL. Since the addition of R results in a 36-fold increase in treatment costs, these observations may be important to decide therapeutic approaches in NHL patients living in underprivileged circumstances. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is an autoimmune disease mediated by antibodies to acetylcholine receptors (AChRs) or muscle specific tyrosine kinase (MuSK). While the frequent association of MG with thymoma in patients aged 40-60 years is well recognized, its occurrence in patients with lymphoma has not been well studied. We review the literature on the association of MG and lymphoid malignancies and report two new patients. MG can occur in a synchronous or non-synchronous fashion with lymphoma. The pathogenesis of MG in lymphoid malignancies is probably heterogeneous and likely relates to perturbations in the immune mechanisms that normally prevent the emergence of autoimmunity. These perturbations could be the result of the lymphoid malignancy per se, or its treatment. [ABSTRACT FROM AUTHOR]

The interaction between CXCR4 on the surface of tumor cells and CXCL12 in the stroma is believed to contribute to tumor cell survival and protection against drug treatment. Inhibition of stromal survival signals by CXCR4 antagonists has been reported to render tumor cells more sensitive to chemotherapy, but little is known about potential synergy with monoclonal antibodies. In this study, administration of the small molecule CXCR4 antagonists plerixafor and GENZ-644494 was found to enhance the anti-tumor activity of the monoclonal antibodies alemtuzumab and rituximab in disseminated lymphoma models. The observed enhancement in therapeutic efficacy by CXCR4 antagonists appeared to involve several factors, including interference with the tumor-promoting signals delivered by CXCL12, disruption of the tumor/stroma interaction and mobilization of effector neutrophils capable of mediating antibody-dependent cell-mediated cytotoxicity. The involvement of neutrophils was further supported by the observed reversal in therapeutic benefit upon neutrophil depletion. [ABSTRACT FROM AUTHOR]

Several studies have reported a higher prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) than in the general population. Treatment for NHL includes the use of chemotherapeutic agents such as cytotoxic drugs, corticosteroids, and rituximab, which can be immunosuppressive and hepatotoxic. While reactivation of hepatitis B virus (HBV) when undergoing immunosuppressive therapy for haematological malignancies is a well-documented complication, data on HCV reactivation or liver function impairment after chemotherapy for NHL are controversial. From January 2006 to December 2009, 207 consecutive NHL patients treated with chemotherapy without rituximab (CHOP) or with rituximab (R-CHOP) were observed; screening for HCV infection and baseline liver function tests were performed in all patients. The prevalence of HCV infection was 9.2%. This prevalence is higher than that observed in the general population in Italy (3%). Among the HCV-infected subjects, the incidence of hepatitis flares was 26.3% vs 2.1% among the HCV-uninfected individuals. Although less frequent and less severe than in HBV-infected subjects, liver dysfunction can occur as a consequence of rituximab-containing regimens in HCV-infected patients with NHL. In the cases considered in this study, no patient treated with chemotherapy without rituximab developed hepatitis flares. The frequency and the severity of this complication vary in different reports. Therefore, we recommend the assessment of liver function and the screening of all patients with NHL for HCV infection before starting chemotherapy; we also recommend monitoring of liver function tests and HCV-RNA serum levels during treatment. [ABSTRACT FROM AUTHOR]

We aimed to assess quality of life (QoL) following front-line autologous stem cell transplant (ASCT) and the QoL relationship with rituximab maintenance, in patients with diffuse large B-cell lymphoma. Patients were then randomized to either one weekly rituximab injection for 4 weeks, or observation alone. Patients ( n == 269) were given the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaires. Scales for all symptoms exhibited similar temporal patterns, with a marked increase, followed by a plateau after 1 year. The proportion of patients with a clinically significant improvement varied from 6%% (constipation) to 56%% (fatigue). Age, gender, and previous treatment-induced toxicities were not predictive of variations in QoL. Rituximab significantly reduced pain and symptom severity. Our results for QoL showed that patients experienced rapid recovery after ASCT in all the domains tested. Differences in QoL improvement with time were not connected with rituximab maintenance. [ABSTRACT FROM AUTHOR]

Predicting the prognosis of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) has been a moving target over the last several years. While earlier prognostic models relied mainly on such clinical variables as age, stage of disease, and performance status, it has become evident from gene-expression microarray studies that DLBCL is a heterogeneous disease in terms of molecular pathogenesis and cell of origin. Despite providing considerable insight into disease biology, these techniques are not widely available and are, at least at present, not applicable to routine clinical practice. Furthermore, older prognostic models need to be revalidated and modified as improved therapeutic options become available. In this review, we discuss pertinent studies on individual biomarkers and pattern-based biomarker models, with an emphasis on markers evaluated in patients treated with rituximab-containing chemotherapy. We also discuss recent and ongoing therapeutic trials using drugs that target molecular markers and pathways involved in the pathogenesis of DLBCL or those that adversely influence prognosis. The ultimate goal of these efforts is to refine prognostication of DLBCL using widely available, reproducible, and consistently predictive biomarker models applicable to currently used chemoimmunotherapy, and to create a pathophysiologically based framework for the rational design of individually tailored therapy. [ABSTRACT FROM AUTHOR]

Rituximab (anti-CD20 mAb) mediates antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis in B-NHL cells. The contribution of other host-mediated cytotoxic effects has not been examined. The expression of death-inducing ligands (e.g. TRAIL) by host effector cells may contribute to the mechanism of tumor cell destruction in vivo by rituximab-mediated sensitization of resistant B-cell non-Hodgkin lymphoma (B-NHL) cells. We have examined the sensitizing activity of rituximab on B-NHL cell lines resistant to TRAIL (as model) and natural killer (NK)-induced apoptosis. Treatment of TRAIL-resistant B-NHL cell lines with rituximab sensitized the cells to TRAIL apoptosis and synergy was achieved via activation of the type II mitochondrial pathway for apoptosis. Further, rituximab (Fab′)2-treated tumor cells were killed by purified peripheral blood-derived NK cells via TRAIL. Treatment of B-NHL cells with rituximab inhibited both YY1 DNA-binding activity and expression. Rituximab-mediated sensitization to TRAIL apoptosis was due, in large part, to rituximab-mediated inhibition of the transcription factor Yin Yang 1 (YY1). The direct role of YY1 in TRAIL sensitization by rituximab was shown in cells transfected with YY1 siRNA, and such cells mimicked rituximab and became sensitive to TRAIL-induced apoptosis. These data suggest that, in vivo, host effector cells expressing TRAIL may contribute to rituximab-mediated depletion of B-NHL cells. [ABSTRACT FROM AUTHOR]

Fewer than half of patients with diffuse large B-cell lymphoma (DLBCL) can be cured. Molecular prognostic factors in the rituximab era must be re-evaluated, because there are few molecular indicators with prognostic value. Samples of DLBCL from 41 newly diagnosed patients with a median follow-up of 52 months were studied. Immunohistochemical staining was performed to investigate the expression of apoptosis-related proteins (Bcl-2 and caspase 3a), cell proliferation (Ki-67), and tumor microenvironmental factors. Two groups were analysed, 23 cases (56%) treated with CHOP and 18 (44%) treated with R-CHOP. Survival analysis showed that cases with overexpression of Bcl-2 had worse overall survival (OS) in the CHOP group. However, OS in the R-CHOP group was adversely affected by lack of caspase 3a staining. In the entire series, cases positive for caspase 3a showed significantly better OS, without significance for other parameters, and caspase 3 was associated with parameters of prognosis and OS in R-CHOP. This is the first study that relates caspase 3a and prognosis in DLBCL. [ABSTRACT FROM AUTHOR]

We have previously shown that expression of CD40 has a favorable prognostic impact in diffuse large B-cell lymphoma (DLBCL) after anthracycline-based chemotherapy. Here we examined the prognostic value of immunohistochemically defined CD40 expression in 95 patients with DLBCL treated with both anthracycline-based chemotherapy and rituximab. Using a 10% cut-off level, 77% of the patients had CD40-positive tumors and showed a superior overall survival ( p = 0.02 log-rank, hazard ratio 0.35, 95% CI 0.14–0.88, p = 0.03 Cox regression). When adjusted for International Prognostic Index in multivariate analysis, CD40 was not an independent prognostic factor (hazard ratio 0.39, 95% CI 0.15–1.04, p = 0.06 Cox regression). However, even after the introduction of immunochemotherapy, CD40 has a potential prognostic impact in DLBCL. Additional and larger studies are necessary, regarding the immunohistochemical robustness of CD40 and the biological mechanisms that contribute to the superior prognosis in CD40-expressing DLBCL. [ABSTRACT FROM AUTHOR]

The prognosis and management of acute exacerbations of hepatitis-B in patients with lymphoma after chemotherapy in combination with rituximab remain unclear. Here, we describe 19 Chinese patients with lymphoma who suffered this complication, in order to analyze their clinical characteristics. Receiver operating characteristic analysis and Kaplan–Meier survival analysis were utilized to determine potential prognostic factors. We found that key prognostic factors included the peak prothrombin time (PT), international normalized ratio (INR), and total bilirubin (TB), as well as the PT and INR on admission and the interval between acute exacerbation of hepatitis-B and the last cycle of chemotherapy. Moreover, our data suggested that shorter interval between the last cycle of rituximab and acute exacerbation of hepatitis-B might be another prognostic indicator of inferior survival. Our results revealed that the severity of hepatic damage and the interval between the last cycle of chemotherapy and hepatitis flare were the major prognostic factors of an acute exacerbation of hepatitis-B induced by immunochemotherapy. Prophylactic antiviral and rescue antiviral therapy remain to be further characterized. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplant (ASCT) is the standard of care for patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adding rituximab (R) to the initial therapy has improved outcomes; however, the benefit of ASCT for chemosensitive patients who fail R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, prednisone) is unclear. Patients who underwent ASCT between 1997 and 2006 for DLBCL at two partner institutions were identified. Characteristics and outcomes were compared between patients who received R-CHOP as initial chemotherapy and those who received CHOP. Of the 185 patients evaluated, 137 were initially treated with CHOP and 48 received R-CHOP. Patients who received R-CHOP were older, had shorter remissions, and initially had more advanced stage. With univariate analysis, PFS and OS did not differ; however, multivariable Cox regression analysis suggested a poorer prognosis for patients who underwent ASCT after failing R-CHOP. In conclusion, patients who fail R-CHOP appear to benefit from ASCT, but they may have a worse prognosis compared to patients who fail CHOP alone. [ABSTRACT FROM AUTHOR]

More than 60% of patients with diffuse large B-cell lymphoma (DLBCL) will be cured with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, the outcome following secondary therapies remains poor. Early identification of high-risk patients would allow alternative treatment strategies to be considered. Clinical prognostic factors, such as the International Prognostic Index remain useful, but can no longer identify patients with a very poor outcome. Identification of molecular prognostic markers will be required to improve risk stratification. A large number of molecular markers have been reported to be prognostic in patients with DLBCL treated with CHOP, and more recently with R-CHOP. These markers require further validation before clinical utility can be established. Continuous reassessment of clinical and molecular markers in the context of prospective clinical trials is necessary to ensure ongoing relevance. [ABSTRACT FROM AUTHOR]

Rituximab is a chimeric anti-CD20 monoclonal antibody widely used in the treatment of B-cell non-Hodgkin lymphomas (NHL). Most adverse effects are due to infusion-related reactions, and severe respiratory complications are rare. We retrospectively reviewed clinical data and serial imaging studies of five patients with NHL treated with rituximab-containing chemotherapy who developed new pulmonary abnormalities on routine follow-up FDG-PET/CT imaging. None of the patients had pulmonary lymphoma or other pulmonary disease before therapy and all remained asymptomatic during follow-up. New pulmonary interstitial FDG-uptake was detected on follow-up FDG-PET/CT between 1 and 3 months post-treatment, preceded computed tomography abnormalities in one case, and persisted for several months. FDG uptake was linear, subpleural with maximum Standardized uptake value (SUV) from 2.0 to 5.84. Rituximab-containing chemotherapy for NHL may be associated with asymptomatic late pulmonary toxicity characterised by a distinct FDG uptake pattern. Awareness of this finding is important and should not be confused with lymphoma. [ABSTRACT FROM AUTHOR]

Perfluorocarbon microbubbles (MBs) are routinely used as in vivo ultrasound contrast reagent. In addition, there is great interest in the use of MBs for ultrasound-mediated delivery, for example, of drugs and genes. As MB size (1–10 μm) limits their distribution to the vasculature, we aimed to assess the efficiency of targeting MBs to circulating cells using antibodies. Our experiments showed that MBs efficiently bind to erythrocytes and B-lymphoma cells in blood. The maximum binding was reached at a cell/MB ratio of 1:1. Following binding, the cells acquired buoyancy that allowed their easy separation from blood with brief centrifugation. Coating the MBs with DNA did not interfere with binding to cells. Experiments in mice showed that intravenously injected targeted MBs efficiently chased and bound to preinjected target cells in the bloodstream. Our data demonstrate the potential in targeting of blood cells for diagnostics and therapy. [ABSTRACT FROM AUTHOR]

A retrospective analysis of factors influencing survival in patients with primary lymphoma of bone (PLB) treated at a single institution was performed. The records of 30 eligible patients were evaluated for overall survival (OS) as related to age, sex, stage, International Prognostic Index (IPI) score, number of sites involved and type of treatment. There was a significant difference in OS in patients with IPI scores of low (L) and low intermediate (LI) versus high intermediate (HI) (P = 0.0035), regardless of stage. Sex, age, stage and number of sites did not have a significant influence on OS. There was a statistically significant difference in OS favouring use of combined chemotherapy (with or without rituximab) and radiation compared with either modality alone (P = 0.02). The addition of rituximab resulted in a non-significant trend towards improved OS (P = 0.11). With a median follow up of 49 months, 73% of patients are alive 5 years from diagnosis. [ABSTRACT FROM AUTHOR]

The outcome for patients with follicular lymphoma (FL) has substantially improved over the last few years. This improved survival appears to be largely related to the increasingly widespread use of anti-CD20 monoclonal antibody (mAb) rituximab in the therapy of FL today, either in combination with chemotherapy, for remission 'induction' and more recently as 'maintenance' therapy. Encouraging results have also been reported from radiolabelled anti-CD20 mAb or radioimmunotherapy (RIT), which exploits the unique method of action of this approach and high radiosensitivity of FL. High response rates and durable remissions have been seen with both 90Y Ibritumomab tiuxetan and 131I Tositumomab, and more recently compelling data are emerging demonstrating the efficacy of using these drugs as consolidation after initial treatment with chemotherapy or rituximab plus chemotherapy combinations. This review will focus on the current approaches and explore the data that has led to the emergence of a new nomenclature appearing in the language of clinicians involved in the treatment of FL, namely 'induction' therapy, 'consolidation' of initial response and 'maintenance' therapy. The current treatment approaches that have led to such increased optimism regarding the therapeutic outcome in FL are evaluated and discussed. [ABSTRACT FROM AUTHOR]

The addition of rituximab to cyclophosphamide, vincristine and prednisolone (CVP) for advanced follicular lymphoma increases median time to progression by 17 months. A US societal cost-effectiveness of R-CVP versus CVP is estimated for a representative 50-year-old patient. Progression-free survival (PFS) and overall survival are based on a randomized Phase III trial. Costs are estimated using Medicare reimbursement rates and published drug price data, and include drug and administration costs, adverse events, treatment of relapses, and end-of-life care. Utility estimates are derived from the literature and a 3% discount rate is employed. Mean overall survival is projected to be 1.51 years longer for patients assigned to R-CVP versus CVP. The cost per quality-adjusted year of life gained is $28,565. The utility associated with stable or progressive disease and the unit drug cost of rituximab most influence the findings. The cost-effectiveness ratio of R-CVP compared with CVP is projected to be cost-effective in the United States under a range of sensitivity analyses. [ABSTRACT FROM AUTHOR]

Rituximab is effective in about one half of patients with indolent lymphoma. Even these patients relapse and develop rituximab resistance. To increase potency and circumvent resistance, the anti-lymphoma effects of rituximab, an anti-CD20 MAb1, combined with chLym-12, an anti-HLA-DR MAb, were assessed in human lymphoma cell lines by examining growth inhibition and cell death, apoptosis induction, ADCC3 and CDC4. There were additive effects in all assays and synergism in cell lines, such as B35M, which displayed resistance to either MAb alone. In B35M cells, combined rituximab and chLym-1 induced a 27-fold direct reduction in viable cells, whereas equivalent concentrations of rituximab or chLym-1 alone induced only a 1-fold and 10-fold reduction in viable cells, respectively. Because these results occurred at MAb concentrations readily achievable in patients, they suggest that this combination immunotherapy regimen may increase the potency and range of effectiveness of these MAbs in lymphoma patients. [ABSTRACT FROM AUTHOR]

Optimal treatment of cutaneous B-cell lymphoma (CBCL) is yet to be established. We treated five patients, each with either extensive lesions, severe comorbidities or who refused treatment with radiation therapy, with rituximab given as a single agent for four weekly intravenous infusions of 375 mg/m2. Maintenance therapy, if initiated, was given at 375 mg/m2 once every 2 – 3 months. Objective clinical responses occurred in all five patients. Three patients have ongoing complete clinical remissions with a median follow-up of 17, 19 and 39 months post achievement of complete remission. One patient died at age 87 years from a non-related cause after 5.5 years of complete remission. One patient received local radiotherapy to a solitary cutaneous site of large-cell lymphoma that developed after 3 years in remission from the low-grade CBCL; no recurrences of either grade CBCL have yet occurred. Treatment was well tolerated. Rituximab is safe and effective in treating of CBCL, either primary CBCL or low-grade lymphomas with relapses limited to the skin. Rituximab appears to present an attractive alternative when radiation therapy is contraindicated or unwanted. Additional collaborative studies are needed to assess the role of rituximab in various clinicopathologic presentations of CBCL. [ABSTRACT FROM AUTHOR]

Rituximab, an anti-CD20 human-mouse chimeric monoclonal antibody has been shown to improve response rates when it is combined with standard salvage chemotherapy in patients with relapsed or refractory intermediate-grade B-cell non-Hodgkin's lymphoma. A vast majority of these patients subsequently undergo high-dose therapy followed by stem cell transplantation. However, the impact of rituximab on stem cell mobilization kinetics is not well characterized. The purpose of this study was to study the effect of high-dose rituximab given with chemotherapy on stem cell mobilization in patients with intermediate-grade B-cell non-Hodgkin's lymphoma. Thirty-six patients received ifosfamide, etoposide, and rituximab followed by filgrastim for stem cell mobilization. The chemotherapy regimen was well tolerated. Thirty-four of 36 patients (94%) were able to mobilize at least 2 × 106 CD34+ cells/kg body weight after a median of 2 apheresis procedures. The median CD34+ cell dose collected per kilogram of recipient body weight was 6.5 × 106 (range, 4.65-31.15). All patients who subsequently underwent high-dose chemotherapy and stem cell transplantation experienced sustained engraftment. In conclusion, high-dose rituximab given during stem cell mobilization does not negatively affect stem cell mobilization kinetics. [ABSTRACT FROM AUTHOR]

Intravascular lymphoma is a rare aggressive systemic neoplasm with neurological and cutaneous presentation, which commonly eludes the diagnosis ante mortem . We document a case of intravascular lymphoma in a 65-year-old man who presented with altered mental status, fevers and weight loss. The diagnosis was made by random skin biopsies demonstrating an intravascular, CD20 positive cellular infiltrate. Initial treatment consisted of cyclophosphamide, vincristine, doxorubicin, prednisone and rituximab. Because of disease progression, the therapy was switched to weekly rituximab after the first cycle. A complete response was observed with resolution of symptoms and laboratory abnormalities. The patient remains in remission 3 years after completion of therapy. This is the first case report to describe a sustained remission following single-agent rituximab in the patient with neurologic involvement of intravascular lymphoma who failed antracycline-based therapy. Single-agent rituximab has activity in this disease and may be considered as a treatment option. [ABSTRACT FROM AUTHOR]

Although rituximab is an effective and safe therapy for B-cell lymphoid malignancies, a few cases of severe infusion-related reactions have been reported. Severe refractory distributive shock is an infrequent side-effect of treatment with rituximab and, to our knowledge, there are no reports describing its pathogenesis in a case of fatal outcome in detail. We present for the first time a case of fatal rituximab infusion-related refractory distributive shock in a patient with CD5+ diffuse large B-cell lymphoma (DLBCL) and analyse the pathogenic mechanisms involved. We have compared measurements obtained from the patient that experienced lethal refractory shock with the four subsequent DLBCL patients treated with rituximab, either at diagnosis or upon relapse, at our center. Serum cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70] and complement components C3 and C4 were analysed, both pretreatment, and 3 h and 9 h after the onset of infusion. When compared with the control subjects, the potential risk factors for rituximab toxicity displayed by the patient that suffered refractory shock included C4 hypercomplementemia, IFN-γ and IL-10 hypercytokinemia, as well as a high tumor burden. The refractory shock was distributive with most cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6 and IL-8) peaking 3 h after infusion and coinciding with the onset of the shock. Furthermore, the concentrations of IL-10 were persistently elevated. In conclusion, the cytokine pattern was similar to that observed in patients with rapid onset septic shock and serum cytokines reached levels markedly higher than previously described in other cases of severe rituximab infusion-related toxicity. [ABSTRACT FROM AUTHOR]