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The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/– interferon). [ABSTRACT FROM AUTHOR]

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]

The aim of the present study was production of nanostructured lipid carriers (NLCs) of curcumin and imatinib for co-administration in non-Hodgkin lymphoma cells. NLCs were prepared and conjugated to rituximab to target CD20 receptors of lymphoma cell lines. Oleic acid or Labrafac and glyceryl monostearate or lecithin were used for production of NLCs. The antibody coupling efficiency to NLCs and their physical characteristics were studied. The cytotoxicity of NLCs on Jurkat T cells (CD20 receptor negative) and Ramos B cells (CD20 receptor positive) was studied by MTT assay. The cellular uptake was determined by fluorescent microscopy. The results indicated both curcumin and imatinib targeted NLCs had a significant cytotoxic effect much higher than the free drugs and non-targeted NLCs on Ramos cells. In both cell lines, the cytotoxicity of the co-administrated drugs was significantly higher than each drug alone. In Ramos cells the co-administration of curcumin (15 μg/ml)/imatinib (5 μg/ml) decreased the free curcumin IC50 from 8.3 ± 0.9 to 1.9 ± 0.2 μg/ml, and curcumin targeted NLCs from 6.7 ± 0.1 to 1.3 ± 0.2 μg/ml. In this case the IC50 of imatinib was reduced from 11.1 ± 0.7 to 2.3 ± 0.1 μg/ml and imatinib targeted NLCs from 4.3 ± 0.1 to 1.4 ± 0.0 μg/ml. The co-administration of ritoximab conjugated NLCs of curcumin and imatinib may enhance cytotoxicity of imatinib in treatment of non-Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

To identify main qualitative and quantitative changes by spectral-domain optical coherence tomography (SD-OCT) in eyes with vitreoretinal lymphoma (VRL) shifting form active to remission phase, after intravitreal rituximab (IVR).SD-OCT scans retrospectively assessed for: hyperreflective retinal dots (HRD), intraretinal infiltration, subretinal infiltration, outer retina (OR) fuzzy borders, and pigment epithelium detachments (PED).Central macular thickness (CMT) and choroidal thickness (CT) were measured. These features were examined in active and in remission phase.Eighteen eyes of nine patients enrolled. Patients received 5.3 ± 2.1 IVR according to a 2-weekly or monthly schedule. In remission phase, presence of HRD (p = 0.02), intraretinal infiltration (p = 0.02), OR fuzzy borders (p = 0.01) significantly reduced. Treatment frequency did not influence rate of disappearance of these features. CMT (p = 0.04) and CT (P = 0.004) became thinner.Signs referable to lymphoma-induced inflammation (CMT, CT, HRD) and infiltration (intraretinal infiltrates, OR fuzzy borders) decreased in remission phase. Further comparative studies needed to identify the specific role of IVR in inducing these changes. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Indolent B-cell non-Hodgkin lymphomas (iNHLs) are considered incurable. Rituximab maintenance and yttrium-90 ibritumomab tiuxetan (90Y-IT) consolidation are promising post-remission therapies. However, only one randomized phase II trial has compared their efficacies and adverse effects. Here, we compared the efficacy and safety of 90Y-IT consolidation and rituximab maintenance in iNHL patients. METHODS: We retrospectively examined 75 iNHL patients with complete or partial response after initial chemotherapy between January 2008 and December 2018. Twenty-seven patients received 90Y-IT consolidation and 48 received rituximab maintenance (every 2 months for 2 years). Progression-free survival (PFS), overall survival (OS), and time to next treatment (TTNT) were estimated from the start of the treatment, and adverse effects were evaluated. RESULTS: After a median 3.6-year follow-up, the 5-year PFSs of the 90Y-IT consolidation and rituximab maintenance groups were 75.5% and 82.4%, respectively (log-rank test, p = 0.839), and the 5-year OSs were 100% and 97.8%, respectively (log-rank test, p = 0.465). The corresponding median TTNTs were not reached (log-rank test, p = 0.804). The commonest adverse effect with 90Y-IT consolidation was hematotoxicity; lower rates and grades of cytopenia were observed in patients who received rituximab maintenance. Secondary malignancies were observed in 1 patient (4%) who received 90Y-IT consolidation and 2 patients (4.2%) who received rituximab maintenance (Fisher's exact test, p > 0.99). CONCLUSION:90Y-IT consolidation and rituximab maintenance were similar with respect to PFS, OS, and TTNT. However, the features and grades of adverse effects significantly differed. Patient-specific characteristics should be considered when deciding post-remission treatments. [ABSTRACT FROM AUTHOR]

The GALLIUM trial compared obinutuzumab (GA101, G)-based chemotherapy followed by G monotherapy (G + chemo) for up to two years to rituximab (R)-based chemotherapy followed by R monotherapy (R + chemo) for up to two years in previously untreated follicular lymphoma (FL) patients. We estimated the cost-effectiveness of G + chemo versus R + chemo utilizing GALLIUM trial data and published literature. G + chemo had increased drug costs (undiscounted: $135,200 versus $127,700 for R + chemo), representing a relative increase of 5.9%. However, this was offset by a $6,400 lower cost for disease progression. G + chemo led to increased quality-adjusted life years (QALYs) relative to R + chemo of 0.81 (95% credible range, [CR]: 0.22–1.37), and the overall discounted incremental cost was $1,900 (95% CR: −$7,400 to $8,900). The incremental cost-effectiveness ratio was ∼$2,300 per QALY gained, and the results were highly robust to sensitivity analyses. Treatment with G + chemo compared to R + chemo is cost-effective in previously untreated FL patients in the US. [ABSTRACT FROM AUTHOR]

The article offers information on a study regarding rituximab (R) addition to chemotherapy in patients with chronic lymphocytic leukemia (CLL). It mentions that the effectiveness of +R in the first-line treatment of CLL patients is not restricted to selected patients in RCTs. It states that the loss of CD20 and changes in cell surface markers CD55 and CD59, leading to diminished antibody-dependent cellular cytotoxicity and attenuated complement dependent cell lysis.

A 55-year-old woman with concurrent active thyroid orbitopathy and B-cell lymphoma developed acute exacerbation of thyroid orbitopathy after receiving Rituximab, cyclophosphamide, hydroxydaunorubicin, Prednisone (R-CHOP) chemotherapy, presenting with subtotal loss of vision and severe eyelid edema. Intravenous methylprednisolone was fully effective within several hours. Further exacerbations of her orbitopathy were seen following every subsequent chemotherapeutic treatment, but responded well to oral prednisone. This case shows that thyroid orbitopathy may severely and acutely progress after chemotherapy for concurrent B-cell lymphoma. Clinical awareness of this potential complication may prevent blindness in this rare subset of patients. [ABSTRACT FROM AUTHOR]

Chemoimmunotherapy with rituximab improves survival in clinical trials in upfront chronic lymphocytic leukemia (CLL) treatment. This study compared clinical outcomes with and without rituximab added to first-line chemotherapy in a provincial cohort of CLL patients. Between 1973 and 2014, 1345 patients received CLL treatment: 48% with rituximab, 52% chemotherapy alone. Median overall survival (OS) and treatment-free survival (TFS) were significantly longer with rituximab: OS 8.9 vs. 6.2 years, p < .0001; TFS 3.6 vs. 2.1 years, p < .0001. Addition of rituximab to chemotherapy was a strong independent predictor of mortality with a 32% mortality reduction after controlling for co-variates (age, sex, stage, and treatment with purine analogs). This large population-based study complements clinical trial and registry data demonstrating the benefit of adding rituximab to first-line CLL therapy and adds further evidence of the efficacy of rituximab-based chemoimmunotherapy in a real-world setting. [ABSTRACT FROM AUTHOR]

Early-stage follicular lymphoma (FL) can be cured with involved-field radiotherapy (IF-RT); however, many patients relapse in non-irradiated areas. A combined association with chemotherapy could increase treatment efficacy, but toxic effects could be unacceptable. In vitro synergistic effect between rituximab (R) and RT has been observed, but clinical data are limited. We retrospectively analyzed 41 early-stage FL patients receiving R and IF-RT as first-line treatment. We administered R 375mg/m2 weekly for four courses, before or after IF-RT (median dose 24 Gy). Primary outcome was PFS, secondary endpoints were CR rate, OS and safety. All patients achieved CR, after a median follow-up of 46 months only three patients relapsed after 18, 26 and 42 months; estimated 5-year PFS was 90%. We suggest R in association with IF-RT could represent a feasible first-line treatment option for early-stage FL and could increase efficacy without additional toxicity compared to available data about RT alone. [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]

We examined the additional prognostic value for survival of cell-of-origin, andMYC,BCL2andBCL6translocation status to that provided by the International Prognostic Index in newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients treated firstline with rituximab-containing immunochemotherapy. We searched Medline, Premedline, Embase, the Cochrane Library, Web of Science, and ISI Proceedings (2000–2015) and assessed study risk-of-bias using a prognostic study checklist. Forty-four studies of moderate–high risk of bias with 100–712 participants were included. Immunohistochemistry-determined cell-of-origin, andBCL2andBCL6translocation status added no additional prognostic value. Half of the studies on gene expression profiling-determined cell-of-origin andMYCtranslocation status found that germinal center B-cell–like (GCB) and no translocation were associated with better overall survival (OS) whereas the remaining studies found no effect of these covariates. Further studies are required to ensure that biological information assessed using newer technologies can be reliably used for studies that incorporate newer agents targeting distinct molecular abnormalities identified in high-risk DLBCL patients. [ABSTRACT FROM PUBLISHER]

To assess the risk of second primary malignancy (SPM) in patients with gastric mucosa-associated lymphoid tissue (MALT) Lymphoma (GML), we included 175 patients with GML in the present study. The incidence of SPM in the general population, used for reference, was determined from the French network of cancer registries. During the 1442.9 patient-years of follow-up, 29 patients were diagnosed with incident SPM, including five patients diagnosed with gastric cancer (20.1/1000 patient-years). An increased incidence of SPM was observed in patients with GML (standardized incidence ratios [SIR]: 1.71 [1.14–2.45]) compared to the general French population especially for gastric cancer (SIR: 16.1 [5.19–37.56]). This elevated risk of SPM was significantly increased only in patients treated with immuno/chemotherapy but not in patients treated withHelicobacter pylorieradication alone. Long-term follow-up of patients with GML is mandatory even in patients who have achieved complete remission. [ABSTRACT FROM AUTHOR]

The treatment of relapsed aggressive lymphoma remains a challenge. Platinum-containing chemotherapy is standard of care. Gemcitabine/oxaliplatin (Gem-Ox) with or without rituximab (R) is an outpatient regimen with a favorable toxicity profile. This retrospective ‘real world’ study reports outcomes for 44 unselected patients with relapsed/refractory aggressive lymphoma treated with Gem-Ox ± R. 41% had primary refractory disease. The overall response rate (ORR) was 43% with a complete response (CR) of 30%. Response to the prior treatment regimen significantly affected the ORR with only 8% achieving CR if prior remission was <12 months. Grade 3–4 hematological toxicity was common and 22% had febrile neutropenia. Eight patients proceeded to stem cell transplant. Overall, outcomes remain poor with a median overall survival of 8 months. In this high-risk group of patients, Gem-Ox ± R results in similar responses to other more toxic, inpatient regimens and should therefore be considered as second line therapy in relapsed lymphoma. [ABSTRACT FROM AUTHOR]

Survival for transformed follicular lymphoma (tFL) has improved in the rituximab era and the need for upfront stem cell transplantation (SCT) is unclear. We evaluated the outcomes for all patients treated with first-line chemotherapy for histologically-proven tFL at our institution from 2003–2013 (n = 87). The majority of patients (89.7%) did not receive a SCT as part of first-line management. With a median follow-up of 7.8 years the 5-year overall survival (OS) for all patients was 61.7%. Patients treated with R-CHOP without upfront SCT (n = 55/87) had a 5-year OS of 64.3%. In a Cox regression analysis of the entire cohort (n = 87) International Prognostic Index (IPI) risk group and presence of B symptoms at transformation were independently associated with OS in multivariate analysis (MVA). Our analysis confirms the improved survival of tFL in the rituximab era even in the absence of upfront SCT consolidation. [ABSTRACT FROM PUBLISHER]

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of mature B-cell lymphoma. While the majority of patients are cured with immunochemotherapy incorporating the anti-CD20 monoclonal antibody rituximab (R-CHOP), relapsed and refractory patients still have a dismal prognosis. DLBCL subtypes including an aggressive activated B-cell-like (ABC) and a more favorable prognosis germinal center-like (GCB) DLBCL have been identified by gene expression profiling and are characterized by distinct genetic abnormalities and oncogenic pathways. This identification of novel molecular targets is now enabling clinical trials to evaluate more effective personalized approaches to DLBCL therapy. The forkhead transcription factor FOXP1 is highly expressed in the ABC-DLBCL gene signature and has been extensively studied within the context of DLBCL for more than a decade. Here, we review the significance of FOXP1 in the pathogenesis of DLBCL, summarizing data supporting its utility as a prognostic and subtyping marker, its targeting by genetic aberrations, the importance of specific isoforms, and emerging data demonstrating a functional role in lymphoma biology. FOXP1 is one of the critical transcription factors whose deregulated expression makes important contributions to DLBCL pathogenesis. Thus, FOXP1 warrants further study as a potential theranostic in ABC-DLBCL. [ABSTRACT FROM PUBLISHER]

Optimal frontline treatment in younger high tumor-burden risk follicular lymphoma patients remains a challenge given the reduced efficacy of standard immunochemotherapy (R-CHOP) in widespread disease and unclear role of intensive induction. The retrospective non-randomized pair-matched (1:3) analysis compared 48 intermediate/high Follicular Lymphoma International Prognostic Index (FLIPI) patients receiving intensive rituximab sequential chemotherapy (R-SQ) with 144 random controls (R-CHOP) matched for age, FLIPI score, and maintenance delivery. Complete response rates were 91.7% and 74.1%, respectively (p = .038). After a median follow-up of 8.8 (R-SQ) and 6.5 years (R-CHOP), 5-year time to treatment failure, progression-free survival, and overall survival were 80.9%, 83.2%, and 100% and 57.5%, 60.3%, and 92.1% (p = .0044;p = .0047;p = .22), respectively. Intensive treatment was accompanied by higher acute hematologic toxicity and infections, comparable non-hematologic toxicity, and incidence of secondary malignancies. Intensive induction demonstrates superior long-term disease control compared to R-CHOP, with higher acute hematologic toxicity, but without acute treatment-related mortality. Further studies are needed to define ultra-high-risk FL patients benefiting most from treatment intensity. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented discussing the effect of maintaining relative dose intensity of rituximab to cyclophosphamide,doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (R-CHOP) for treating patients with diffuse large B-cell lymphoma (DLBCL).

An exploratory analysis of 75 follicular lymphoma patients treated with obinutuzumab or rituximab induction therapy (IT) for 4 weeks in the phase II GAUSS study aimed to determine whether positron emission tomography (PET) results could predict progression-free survival (PFS) and tumor response. The proportion of patients with a PFS event (progression or death) was higher in those who were PET-positive after IT (assessed using Deauville five-point scale criteria; 35/52, 67%) than PET-negative (5/20, 25%); the hazard ratio for progression or death was 0.25 (95%CI: 0.01–0.64;p = 0.0018). A significant association was also found when PET results were assessed using International Harmonization Project and European Organisation for Research and Treatment of Cancer criteria. Change between baseline and end of IT in values of standardized uptake value and other PET parameters were associated with PFS and response. Validation of these results in prospective studies of larger cohorts is warranted. [ABSTRACT FROM AUTHOR]

The chemoimmunotherapy FCR (fludarabine and cyclophosphamide with rituximab) is the standard first-line treatment for physically fit chronic lymphocytic leukemia (CLL) patients. To assess the risks and benefits, we investigated health-related quality of life (HRQOL). 817 untreated CLL patients received either FC or FCR within the GCLLSG CLL8 trial. The European Organization for Research and Treatment of Cancer Quality of life Questionnaire C30 was sent to all patients at baseline, after 3, 6, and 12 months and then yearly as follow-up. A total of 769 (94%) of 817 patients completed at least one questionnaire. Comparing HRQOL of CLL patients with the general German population, CLL patients’ health declined in most scales except for global health and pain. No major differences in HRQOL were found during treatment or follow-up between both treatment arms. Females were more likely to have treatment-related symptoms than males. Although FCR was associated with more side effects, this did not influence HRQOL. During follow-up after FCR only minor improvement of HRQOL compared with FC was assessed. [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]

The impact of the addition of rituximab to salvage chemotherapy prior to autologous stem cell transplant (ASCT) was evaluated in a retrospective subgroup analysis of NCIC CTG LY.12. Among 414 patients who relapsed following R-CHOP, 96 received salvage chemotherapy alone [R − cohort]; and 318 received rituximab with chemotherapy [R + cohort] following a protocol amendment. The R−cohort had a higher proportion of patients with PS ≥2 and relapse <1 year after R-CHOP. The response rate (45.6% vs. 25.0%,p = 0.0003), CR/CRu (15.7% vs. 4.2%,p = 0.003) and transplantation rate (51.9% vs. 31.3%,p = 0.0004) was higher in the R + cohort. Event-free (27% vs. 22%,p = 0.0954) and overall survival at four years (43% vs. 31%;p = 0.045) were greater in the R + cohort when the patients with best response SD/PD to R-CHOP were excluded. Addition of rituximab to salvage therapy before ASCT appears to improve the response rate, transplantation rate, and overall survival in patients with CD20+ lymphoma who responded to R-CHOP. [ABSTRACT FROM PUBLISHER]

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare DLBCL location variant. We treated 76 PB-DLBCL patients by immuno-chemotherapy, resulting in an 84% sustained complete remission rate and a 78.9% survival over a 4.7-year median follow-up period. Ann Arbor stage IV and high age-adjusted international prognostic index were predictive of adverse outcome in univariate analysis. In multivariate analysis using a Cox model, only aa-IPI predicted long-term survival. While based on a limited number of cases, we suggested that radiotherapy may be useful as a consolidation modality in PB-DLBCL. We also suggested that positron emission tomography/CT scan should be interpreted with caution due to a persistent [18F]fluorodeoxyglucose [18FDG] uptake of bone lesions even after remission in some in PB-DLBCL patients. Our study based on a homogeneous cohort of PB-DLBCL patients confirmed the favorable outcome of this DLBCL variant and support the implementation of prospective clinical trials in this disease. [ABSTRACT FROM AUTHOR]

Renal involvement in patients with lymphoma is rare but associated with poor prognosis. We analyzed characteristics and outcome of 22 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and renal involvement treated with a rituximab-containing regimen in curative intent. The majority of patients presented in advanced disease, 86% were Ann Arbor stage ≥ III and had an IPI score ≥ 3. Renal impairment was present in 32%. Outcome was poor with three-year progression-free survival (PFS) 44% and three-year overall survival (OS) 52% and significantly worse compared to DLBCL without renal involvement (p < 0.01). Patients with high-risk IPI had a significantly inferior prognosis compared to intermediate-risk IPI (three-year OS 0% vs. 75%,p = 0.01) as did those with renal impairment. A high rate of central nervous system (CNS) relapse (8/22) was observed. Intravenous high-dose methotrexate and intrathecal therapy showed a trend toward prolonged time to CNS relapse. Implementation of CNS prophylaxis might therefore be considered in these high-risk patients. [ABSTRACT FROM PUBLISHER]

The article discusses the overexpression of BCL2L12 protein associated with favorable outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab. The study included formalin-fixed paraffin-embedded tissue biopsies from newly diagnosed DLBCL patients, and other conventional chemotherapy treatments like cyclophosphamide, doxorubicin, and vincristine. Assessments performed include immunohistochemistry, RNA isolation from cultured cells, and multivariate Cox regression.

The article offers information on the study that investigates the effectiveness of rituximab immunochemotherapy in treating the B-cell non-Hodgkin lymphoma patients who received hemodialysis in Japan. The topics discussed include the percentage of patients who receive chronic dialysis, the safety and tolerability of rituximab immunochemotherapy, and the chronic dialysis risk factors.

Objective and importance: Hodgkin's lymphoma (HL) is a well-curable disease. The treatment usually includes combined multiagent conventional chemotherapy and radiotherapy. One-fifth of the patients need repeated treatments because of relapse or primary progressive disease. Those HL patients, who cannot be cured at least with salvage therapy (including autologous haemopoietic stem cell transplantation (auto-HSCT)), have really unfavourable prognosis. Intervention: For this heavily pretreated subset of HL patients, novel but less toxic treatment strategies should be considered. Brentuximab-vedotin (BV) is a novel targeted treatment option, which was administered after the failure of two different regimens in patients, who were ineligible for auto-HSCT or after the failure of auto- HSCT. Moreover, there are favourable data with chemotherapeutical regimens supplemented with rituximab not only in relapsed but also in newly diagnosed classical HL patients. Bendamustine, an almost forgotten 50-year-old drug, lives its renaissance in the twenty-first century, which can be administered in refractory HL as well. Combination of the 'new' and 'old' drugs might be also helpful. Conclusion: Our data suggest that rituximab plus bendamustine (supplemented with or without BV) could be a suitable alternative bridging salvage therapy for heavily pretreated HL patients. [ABSTRACT FROM AUTHOR]

We assessed fertility/gonadal function in premenopausal women treated with dose-adjusted EPOCH-Rituximab for untreated primary mediastinal B-cell lymphoma (PMBL). Eligible patents were ≤ 50 years and premenopausal. Serial reproductive histories were obtained and hormonal assays were performed on serum samples before, at the end of treatment and 4–18 months later. Twenty-eight eligible women had a median age (range) of 31 (21–50) years and were followed a median of 7.3 years. Of 23 patients who completed a questionnaire, 19 (83%) were and four were not menstruating prior to chemotherapy. Amenorrhea developed in 12 patients during chemotherapy. At > 1-year follow-up, 14/19 (74%) patients were menstruating, all < 35 years old, and six (43%) of these patients delivered healthy children. Hormonal assays showed ovarian dysfunction during chemotherapy in all patients with varying recovery at 4–18 months after treatment. Fertility was preserved in most women with ovarian failure confined to patients > 40 years old. [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]

The risk of developing non-Hodgkin lymphoma increases with age, yet elderly patients are under-represented in clinical trials. Here, we evaluate a combination regimen including ifosfamide, carboplatin and etoposide with or without rituximab (ICE ± R) in 32 fit elderly patients (median age 75.6 years) with relapsed or refractory diffuse large B-cell lymphoma. ICE ± R was generally administered in reduced doses and was well tolerated. The overall response rate (ORR) was 53.1% with a complete response (CR) rate of 40.6%. The median progression free survival (PFS) and overall survival (OS) were 3.9 and 17.0 months, respectively. Patients who responded to ICE ± R achieved median PFS of 47.2 months and OS of 78.9 months. Patients ineligible for autologous transplantation who responded to ICE ± R were treated with additional cycles, and achieved a median PFS of 18.9 months and OS of 21.7 months. Previous response to first-line therapy was the strongest predictor of response, PFS and OS to second-line treatment. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to impact of strategies regarding rituximab-combined chemotherapy on hepatitis C virus (HCV) viremia, and presents diagrams for the same. Topics discussed include treatment of non-Hodgkin lymphomas (NHLs) using monoclonal antibody rituximab; rise in alanine aminotransferase (ALT) level after starting rituximab-containing induction therapy; and prevention of HCV exacerbation using antiviral therapy before taking chemotherapy.

The cost-effectiveness of rituximab in combination with fludarabine/cyclophosphamide (R-FC) for the first line treatment of chronic lymphocytic leukemia (CLL) was evaluated. Based on long-term clinical data (follow-up of 5.9 years) from the CLL8-trial, a Markov-model with three health states (Free from disease progression, Progressive disease, Death) was used to evaluate the cost per quality-adjusted life-year (QALY) and cost per life years gained (LYG) of R-FC from the perspective of the German statutory health insurance (SHI). The addition of rituximab to FC chemotherapy results in a gain of 1.1 quality-adjusted life-years. The incremental cost-effectiveness ratio (ICER) of R-FC compared with FC was €17 979 per QALY (€15 773 per LYG). Results were robust in deterministic and probabilistic sensitivity analyses. From the German SHI perspective, rituximab in combination with FC chemotherapy represents good value for first-line treatment of patients with CLL and compares favorably with chemotherapy alone. [ABSTRACT FROM AUTHOR]

As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA-EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH-R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes. [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disorder (PTLD) is a rare, serious complication following solid organ transplantation, with an incidence of 2.6 cases per 1000 patient years. Optimal treatment strategies and risk stratifications specific to kidney transplantation are lacking and PTLD mortality remains high. This study investigated survival and prognosis in 89 cases of PTLD presenting over 44 years at Manchester Royal Infirmary. Patient survival following diagnosis was 72% at 6 months, 67% at 1 year and 54% at 3 years. In multivariate analysis, a poorer 3 year survival was associated with acute kidney injury at diagnosis (p= 0.0001), impaired renal function (p= 0.04), early onset (p= 0.02), T cell disease (p= 0.02) and previous treatment with anti-thymocyte globulin (p= 0.04). The inclusion of graft function adds prognostic value to risk stratification and should be explored further. Strategies to improve survival should include timing and choice of immuno-chemotherapy, preparation for dialysis and aggressive surveillance for sepsis and treatment toxicity. [ABSTRACT FROM PUBLISHER]

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]

The optimal treatment of follicular lymphoma (FL) is not established. Rituximab’s value potentially dilutes the impact of chemotherapy on FL. We reviewed 337 cases of FL treated initially with rituximab as monotherapy or with chemotherapy at the University of Iowa/Mayo Clinic from 2002 to 2009, investigating the association between chemotherapy delivery of cyclophosphamide or doxorubicin and survival. With median follow-up duration of 52.7 months, event-free survival (EFS) and overall survival (OS) were similar between the two groups, with a trend toward better EFS in the R-chemotherapy cohort (hazard ratio [HR] = 1.24,p= 0.28). In the R-chemotherapy group, increased total dose delivery and delivered dose intensity of doxorubicin were associated with improved EFS only in patients who did not receive R-maintenance (HR = 0.81;p= 0.02 and HR = 0.94;p= 0.04). Cyclophosphamide delivery was not associated with EFS. Thus, in the immunochemotherapy era, chemotherapy delivery strategy requires re-evaluation. [ABSTRACT FROM PUBLISHER]

Reactivation of hepatitis B virus (HBV) following rituximab (R)-containing chemotherapy for lymphoma is a major concern, and risk factors remain to be defined. We enrolled 190 patients diagnosed with diffuse large B-cell lymphoma (DLBCL) and resolved hepatitis B, receiving first-line R-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based regimens. Twenty-seven patients (14.2%) developed HBV reactivation during a median follow-up of 23.6 months. Two independent risk factors were identified: cycles of rituximab > 8 (hazard ratio [HR], 2.797; 95% confidence interval [CI], 1.184–6.612) and lymphocyte/monocyte ratio (LMR) < 2.50 (HR, 2.733; 95% CI, 1.122–6.657). Two-year overall survival in patients with or without HBV reactivation was 53.8% vs. 77.6% (p= 0.025). Regarding the negative impact on clinical outcome, patients at “super high risk” of HBV reactivation, including those receiving more than eight cycles of R and having low LMR at diagnosis, may warrant first priority for antiviral prophylaxis. [ABSTRACT FROM PUBLISHER]

The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification ofBRAFV600E mutations and the role of aberrantMEKkinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox),BRAFinhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL. [ABSTRACT FROM PUBLISHER]

Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive non-Hodgkin lymphoma, accounting for 30-40% of newly diagnosed cases. Obesity is a well-defined risk factor for DLBCL. However, the impact of body mass index (BMI) on DLBCL prognosis is controversial. Recent studies suggest that skeletal muscle wasting (sarcopenia) or loss of fat mass can be detected by computed tomography (CT) images and is useful for predicting the clinical outcome in several types of cancer including DLBCL. Several hypotheses have been proposed to explain the differences in DLBCL outcome according to BMI or weight that include tolerance to treatment, inflammatory background and chemotherapy or rituximab metabolism. In this review, we summarize the available literature, addressing the impact and physiopathological relevance of simple anthropometric tools including BMI and tissue distribution measurements. We also discuss their relationship with other nutritional parameters and their potential role in the management of patients with DLBCL. [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]

Objectives The randomized phase 3 PRIMA trial established that 2 years of rituximab maintenance therapy after attaining disease response to immunochemotherapy as first-line treatment of follicular lymphoma, reduced the risk of disease progression, compared with observation, without adversely affecting patient-reported quality of life (QoL). We now report additional analyses of symptom burden and toxicity. Methods Symptom burden was measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 items. The proportion of patients with worsening, no change, or improvement in symptoms from maintenance baseline was compared between rituximab maintenance and observation groups with Pearson χ2 tests. Improvement in symptoms after 1 and 2 years of maintenance was further analyzed using generalized mixed models. The adverse event (AE) rate was calculated from the toxicity checklist at each visit to explore the frequency and timing of the toxicity AE in each treatment arm. The study protocol was approved by local ethics committees and is registered at ClinicalTrials.gov under NCT00140582. Results Being tired, needing to rest, feeling weak, and trouble sleeping were the most frequently reported symptoms at the end of immunochemotherapy. By the end of maintenance, notable improvement was seen for fatigue symptoms, trouble sleeping, shortness of breath, lack of appetite, and nausea, with no significant difference in QoL symptoms between the rituximab maintenance and observation groups. The rate of AEs was low, and hematologic toxicity induced during chemotherapy treatment improved in both rituximab maintenance and observation groups. Discussion These results indicated that rituximab maintenance did not negatively impact disease- or treatment-related symptoms. [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]

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma (NHL). While the de facto treatment standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) is curative in most cases, it is ineffective for a significant proportion of patients, particularly those with intermediate and high-risk disease. Efforts to improve upon the results of R-CHOP have principally explored dose intensification of chemotherapy and resulted in considerable additive toxicity without clear benefit. DLBCL is not a uniform disease, however, and can be dissected into distinct molecular subtypes by gene expression profiling. These subtypes are characterized by distinct oncogenic mechanisms of activation and addictions to aberrant intracellular signaling pathways. Novel therapeutic agents that target these pathway addictions are emerging, and may have specific activity within molecular subtypes of DLBCL. To move beyond R-CHOP for all patients with DLBCL, targeted therapies added to the most effective chemotherapy platforms must be studied within the context of molecularly defined subsets. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is characterized by an initial response to treatment with inevitable relapse. We evaluated chemoimmunotherapy resistance (CIR resistance) including transformation. We identified patients who received rituximab combination therapy for symptomatic FL. CIR resistance was defined as disease progression during rituximab-based chemoimmunotherapy, rituximab maintenance or within 6 months of treatment completion. Our primary outcome was time to early progression (CIR resistance). Between July 2006 and April 2010, 132 patients met the inclusion criteria and 22 (16.7%) demonstrated CIR resistance with a median follow-up of 33 months. High-risk Follicular Lymphoma International Prognostic Index (FLIPI) score was predictive of CIR resistance (hazard ratio [HR] 2.43; 95% confidence interval [CI], 1.4-4.1; p = 0.001). Overall, eight patients (36.3%) transformed (biopsy-proven), with no transformation in the chemoimmunotherapy responder group. Median overall survival in the CIR resistant group was 47 months. Patients with CIR resistance had high rates of histologic transformation and shorter survival with poor response to next therapy. [ABSTRACT FROM AUTHOR]

The results of intensive immunochemotherapy were analyzed in human immunodeficiency virus (HIV)-related Burkitt lymphoma/leukemia (BLL) in two cohorts (Spain and Germany). Alternating cycles of chemotherapy were administered, with dose reductions for patients over 55 years. Eighty percent of patients achieved remission, 11% died during induction, 9% failed and 7% died in remission. Four-year overall survival (OS) and progression-free survival (PFS) probabilities were 72% (95% confidence interval [CI]: 62-82%) and 71% (95% CI: 61-81%). CD4 T-cell count < 200/μL and bone marrow involvement were associated with poor OS (hazard ratio [HR] 3.2 [1.2-8.3] and HR 2.7 [1.1-6.6]) and PFS (HR 3.5 [1.3-9.1] and HR 2.4 [1-5.7]), bone marrow involvement with poor disease-free survival (DFS) (HR 14.4 [1.7-119.7] and Eastern Cooperative Oncology Group (ECOG) score > 2 (odds ratio [OR] 11.9 [1.4-99.9]) with induction death. In HIV-related BLL, intensive immunochemotherapy was feasible and effective, but toxic. Prognostic factors were performance status, CD4 T-cell count and bone marrow involvement. [ABSTRACT FROM AUTHOR]

High dose chemotherapy with autologous stem cell transplant (HD-ASCT) is a recommended procedure for patients with transformed indolent B-cell lymphoma from the pre-rituximab era. In this retrospective single-center study, we present our experience with HD-ASCT in patients with histologically verified transformed indolent B-cell lymphoma in the rituximab era. Forty-two patients were included, of whom 28 with chemosensitive disease proceeded to HD-ASCT. Twenty patients (71%) achieved a complete response (CR) and five (18%) a partial response (PR) after HD-ASCT. With a median observation time of 49 months for the survivors, the median progression-free survival (PFS) and overall survival (OS) for patients with HD-ASCT were 39 months and 57 months, respectively. Patients who were rituximab-naive at transformation had a significantly better OS compared to patients previously treated with rituximab, both in the whole patient cohort and among the HD-ASCT-treated patients ( p = 0.036 and p = 0.039, respectively). Furthermore, male sex influenced survival negatively, whereas time from diagnosis to transformation was positively associated with survival, both with borderline significance, in HD-ASCT-treated patients. In conclusion, HD-ASCT remains an effective treatment for transformed indolent lymphomas in the rituximab era. [ABSTRACT FROM AUTHOR]

Novelty and Impact: This first study compares the survival of HCV-positive DLBCL treated with and without rituximab which showed in toxicity and the outcome. Background: The effect of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era is unclear. The treatment and the outcome of patients with DLBCL and HCV infection are still a matter of debate. Methods: We analyzed 137 DLBCL patients positive to HCV, treated with chemotherapy regimens include cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab. Survival outcomes and hepatic toxicity were compared in DLBCL patients positive to HCV infection according to CHOP ± rituximab. Result: Our result showed that the group of patients treated with R-CHOP has significant high incidence of hepatic toxicity grade (3–4) (28 vs. 18%, P value 0.001) and worse progression-free survival (55 vs. 80%, P value 0.002) in comparison with the group treated with CHOP, and also there is significant difference between both groups in overall survival. This first study compares the survival of HCV-positive DLBCL treated with and without rituximab which showed significant differences. Conclusion:We conclude that HCV-positive patients with DLBCL treated with rituximab plus CHOP have high incidence in hepatic toxicity. Specific protocols evaluating antiviral therapy should be designed for these patients [ABSTRACT FROM AUTHOR]

The article presents a case study of a 28-year-old white woman with achildhood diagnosis of Rubinstein-Taybi syndrome (RTS) who developed progressive head and neck lymphadenopathy. The patient's cervical lymph node biopsy revealed follicular lymphoma (FL) and symptomatic improvement was observed on the initation of chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) with rituximab. The biology of RTS and importance of genetic testing in the diagnosis of RTS are explained.

Splenic marginal zone lymphoma (SMZL) is a rare chronic B-cell lymphoproliferative disorder recognized as a distinct entity in the World Health Organization (WHO) classification. SMZL usually runs an indolent clinical course with a median survival of more than 10 years. However, in a proportion of patients (10-20%) SMZL behaves more aggressively, with a median survival of less than 4 years. Many efforts are ongoing to establish commonly accepted prognostic factors as a guide to therapy for this disorder. Data on the treatment of SMZL come from reported retrospective series including relatively limited numbers of patients. Despite these limitations, much progress has recently been made in the management of patients with SMZL. The oldest and most commonly used first-line therapeutic modality is splenectomy, which offers rapid alleviation of splenomegaly-related symptoms along with an improvement of cytopenias in the majority of patients, with a median PFS of 5 years. However, SMZL is a systemic disease, and splenectomy is not carried out with eradicative intent. Furthermore, splenectomy is a major surgical procedure with significant morbidity or even mortality, especially in older patients. Chemotherapy has only moderate activity in this form of MZL. Recent data suggest that rituximab is a very effective therapy with minimal toxicity and could replace splenectomy as first-line treatment. The overall response rate is > 90%, with almost half of responses being complete, while the 5-year progression-free survival is approximately 70%. The combination of rituximab with chemotherapy requires further evaluation. Based on the current data, splenectomy could be abandoned as first-line treatment for patients with SMZL. [ABSTRACT FROM AUTHOR]