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Patient-specific primers from 10 children/adolescents with Burkitt leukaemia (BL) ± central nervous system disease who were treated with French-British-American/Lymphome Malins de Burkitt 96 C1 plus rituximab were developed from diagnostic blood/bone marrow. Minimal residual disease ( MRD) was assessed by real-time polymerase chain reaction at the end of induction ( EOI) and consolidation ( EOC). Seventy per cent (7/10) and 71% (5/7) were MRD-positive at EOI and EOC, respectively, with no disease recurrences. MRD after induction and consolidation did not predict relapse and subsequent therapy appeared to eliminate MRD. Thus, assessing MRD at a later time point is warranted in future trials to determine its clinical significance. [ABSTRACT FROM AUTHOR]

Summary: Background: Thyroid eye disease (TED) is an autoimmune inflammatory disease that can be disfiguring and potentially sight threatening. Suppression of inflammation in active disease can reduce the risk of visual loss and limit long‐term sequelae. Current management involves inflammation suppression using glucocorticoids. The aim of this study was to evaluate the efficacy of early disease intervention with targeted immunomodulatory therapy to alter disease course. This paper reports the efficacy of low‐dose rituximab in reducing clinical activity in TED in a small population. Methods: A retrospective audit of consecutive patients with active TED managed primarily with a 100 mg rituximab infusion. Further glucocorticoid or steroid‐sparing agents were prescribed if clinically indicated. Clinical activity score, VISA overall severity score and Oxford Quality of Life score were recorded at each visit as well as TSH receptor antibody levels (TRAb), B cell subsets and adverse reactions. Results: Twelve patients had mean follow‐up of 6.3 months. Clinical activity scores significantly decreased (mean score 5.08 to 1.58; P < 0.001), VISA overall severity scores reduced by 50% from 12 to 6, P < 0.001 and the mean cumulative dose of IV methylprednisolone was 2.3 g. 100 mg rituximab induced significant CD19+ B cell depletion (n = 8, P < 0.001). There was no significant reduction in serum TRAb (n = 8, P = 0.06). A transient infusion‐related rash was the only adverse effect, n = 4. QoL scores did not differ markedly before and after treatment. Conclusion: Low‐dose rituximab is an efficacious, well‐tolerated and safe treatment for active TED; reducing disease activity and allowing reduced administration of systemic steroid. [ABSTRACT FROM AUTHOR]

Objective: This systematic review evaluated the efficacy of immunobiologics for the management of oral disease in Sjögren's syndrome (SS). Materials and Methods: MEDLINE®, Embase, Scopus, and the Cochrane Library were searched for evidence on the use of immunobiologics for management of glandular disease in SS. Primary outcomes were xerostomia and salivary gland dysfunction, assessed via visual analogue scales, disease‐specific scales for SS, measurement of salivary flow, ultrasound data, and quality of life measures. Results: Seventeen studies (11 randomized controlled trials and 6 observational studies) met inclusion criteria. Rituximab showed efficacy in improving salivary gland function but not xerostomia. Abatacept showed promise in improving both xerostomia and salivary flow. Belimumab exhibited long‐term improvement of salivary flow and subjective measures. The novel agent CFZ533 improved both disease activity and patient‐reported indexes. Conclusions: There is strong evidence pointing to the efficacy of rituximab in the management of oral disease in SS. Future controlled trials may elucidate the efficacy of belimumab and abatacept. The new drug CFZ533 is a promising alternative for the management of SS and its salivary gland involvement. In considering these agents, the promise of efficacy must be balanced against the harmful effects associated with biologic agents. [ABSTRACT FROM AUTHOR]

The development of inhibitory antibodies to factor VIII ( FVIII) or factor IX ( FIX) in patients with haemophilia is a serious complication of treatment with coagulation factor concentrates. Antibodies develop in 10-15% of haemophilia A and in up to 5% of haemophilia B patients. Several strategies have been developed over the years to facilitate the eradication of inhibitors and reduce the cost. These include plasmapheresis and/or extracorporeal protein A absorption to remove the inhibitor from the plasma, and immunosuppression and/or immune modulation to suppress the production of inhibitory antibodies. Different immunosuppressive ( IS) agents have been described with varying success. To evaluate the outcome of these agents, we performed a systematic literature review using the PubMed database. The total number of articles identified was 345; 299 papers were excluded leaving 46 papers to be included in the study. No randomised studies were identified, only case reports and case series. The most frequently used agents in the 46 case reports and cohort studies identified were cyclophosphamide and rituximab. All cases exposed to cyclophosphamide, rituximab and other IS agents had a complete success rate of 40-44%, 40-63% and 33-56%, respectively. However, the definition of success was not consistent among the studies. In conclusion, our review of the literature indicates that IS agents in combination with FVIII or FIX could be an option and may be cost-effective in many patients. The risk of adverse events seems to be relatively low. To fully explore the effect of IS agents, randomised studies are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Background: Rituximab, an anti‐CD20 B‐cell depleting monoclonal antibody, is increasingly prescribed off‐label for a range of autoimmune diseases. There has not previously been an audit of off‐label rituximab use in the Northern Territory, where the majority of patients are Aboriginal. Aims: To evaluate retrospectively off‐label rituximab use in autoimmune diseases in the Top End of the Northern Territory. Methods: We performed a retrospective audit of 8 years of off‐label rituximab use at the Royal Darwin Hospital, the sole tertiary referral centre for the Darwin, Katherine and East Arnhem regions. Electronic and paper records were reviewed for demographic information, diagnosis/indication for rituximab, doses, previous/concomitant immunosuppression, clinical outcomes and specific adverse events. Results: Rituximab was prescribed off‐label to 66 patients for 24 autoimmune diseases. The majority of patients (62.1%) were Aboriginal and 60.6% female. The most common indications were refractory/relapsing disease despite standard therapies (68.7%) or severe disease with rituximab incorporated into an induction immunosuppressive regimen (19.4%). Systemic lupus erythematosus was the underlying diagnosis in 28.8% of cases. A clinically significant response was demonstrated in 74.2% of cases overall. There were 18 clinically significant infections; however, 13 were in patients receiving concurrent immunosuppressive therapy. There was a total of nine deaths from any cause. Conclusion: Rituximab has been used off‐label for a range of autoimmune diseases in this population with a high proportion of Aboriginal patients successfully and safely in the majority of cases. [ABSTRACT FROM AUTHOR]

Chemoimmunotherapy followed by autologous stem cell transplantation ( ASCT) is a standard therapy for transplant-eligible patients with newly diagnosed mantle cell lymphoma ( MCL). The achievement of complete remission ( CR) and minimal residual disease ( MRD) negativity are associated with better outcomes. We tested an induction regimen of rituximab/bendamustine followed by rituximab/high-dose cytarabine ( RB/ RC). This phase 2 study ( NCT01661881) enrolled 23 transplant-eligible patients aged 42-69, of whom 70% were MCL international prognostic index low-risk. Patients received three cycles of RB followed by three cycles of RC. The primary endpoint of the trial was the rate of CR after six cycles of therapy, with a rate of 75% considered promising. 96% of patients achieved a CR/unconfirmed CR after treatment, meeting the primary objective. One patient progressed on study, one declined ASCT in CR, and the remaining 21 underwent successful stem cell collection and ASCT. After a median follow-up of 13 months, the progression-free survival rate was 96%. Among 15 MRD -evaluable patients who completed treatment, 93% achieved MRD negativity after RB/ RC. In conclusion, RB/ RC achieves very high CR and MRD negativity rates in transplant-eligible patients, with a favourable safety profile. RB/ RC warrants further comparative studies, and may become a useful alternative to RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-based induction regimens in this patient population. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of rituximab (RTX) on lung function and the prevalence of adverse events (AEs) in connective tissue disease‐associated interstitial lung disease (CTD‐ILD) by meta‐analysis. Methods: EMBASE, Web of Science, PubMed and ClinicalKey were searched up to July 16, 2021. The lung function (forced vital capacity, FVC% predicted, and diffusing capacity of the lung for carbon monoxide, DLCO% predicted) and prevalence of AEs of RTX in CTD‐ILD were analyzed by meta‐analysis, and 95% confidence interval (CI) was calculated. Subgroup analyses and meta‐regression were used to explore the heterogeneity. Results: We identified 29 studies, including 827 CTD‐ILD patients with a median age of 53.05 years. In observational studies, FVC% (mean difference − 1.24, 95% CI [−2.35, −0.12]; P =.030) and DLCO% (−7.71, [−11.79, −3.63]; P =.014) of CTD‐ILD decreased significantly after RTX treatment. In randomized controlled trials, FVC% of CTD‐ILD decreased after RTX treatment (−5.24, [−9.94, − 0.54]; P =.029), but the difference of DLCO% was not significant (1.15, [−4.33, 6.63]; P =.681). The prevalence of AEs, all‐cause mortality and infections was 29.7% (95% CI [0.17, 0.42]), 11.6% (95% CI [0.08, 0.16]) and 20.9% (95% CI [0.15, 0.27]), respectively. Conclusions: RTX was associated with AEs such as decreased pulmonary function, all‐cause mortality, and infections in CTD‐ILD. Adverse reactions during and after RTX treatment should be carefully monitored. Further prospective studies are needed to compare RTX with other immunosuppressants, antifibrotic drugs or placebos, which can provide therapeutic approaches for CTD‐ILD. [ABSTRACT FROM AUTHOR]

In this article, the author talks about anti-MAG neuropathy history. Topics discussed include combination of rituximab and fludarabine treatment in IgM antimyelin associated glycoprotein neuropathy, the use of the treatment for oncology rather than neurology and monoclonal gammopathy in the anti-MAG group.

We treated PR3‐ANCA positive vasculitis in a patient diagnosed with rheumatoid arthritis using rituximab. Monoclonal antibody therapy can be used to simultaneous treat more than one collagen disease in such patients. This suggests that shared pathogenic pathways exist between different collagen diseases. [ABSTRACT FROM AUTHOR]

The uveitides are a heterogenous group of ocular inflammatory disorders that account for the third highest cause of blindness worldwide, responsible for 5–10% of visual impairment globally. Up to 35% of patients with uveitis can suffer significant vision loss. To prevent irreversible structural damage and blindness, it is important that the diagnosis and commencement of appropriate therapy occurs promptly. Management includes topical and systemic corticosteroid therapy and conventional immunomodulatory agents, including methotrexate, azathioprine, mycophenolate mofetil and cyclosporin. Significant progress has been made in the past decade in our understanding of the immunopathological pathways that drive intraocular inflammation, allowing the development of targeted therapy with biologic agents. These include TNF‐α inhibitors, such as infliximab, adalimumab and etanercept; interleukin blockers, such as tocilizumab and daclizumab; and other targeted therapies, such as rituximab and abatacept. The efficacy of these agents has been studied in cases of severe uveitis that are refractory to conventional immunomodulatory agents and provide exciting results that have revolutionised uveitis management. Though the biologic era has provided a large armamentarium to treat uveitis, ongoing challenges and cases of recalcitrant uveitis remain, posing a challenge to internal medicine physicians. This comprehensive review aims to construct an updated summary on the existing evidence pertaining to the use of biologic agents in the treatment of uveitis. Methods include a systematic search for studies between 2000 and 2018 using PubMed, EMBASE, Ovid MEDLINE and Cochrane libraries. [ABSTRACT FROM AUTHOR]

The study was undertaken in order to provide a snapshot from real clinical practice of virological presentation and outcome of patients developing immunosuppression‐driven HBV reactivation. Seventy patients with HBV reactivation were included (66.2% treated with rituximab, 10% with corticosteroids and 23.8% with other immunosuppressive drugs). Following HBV reactivation, patients received anti‐HBV treatment for a median (IQR) follow‐up of 31(13‐47) months. At baseline‐screening, 72.9% of patients were HBsAg‐negative and 27.1% HBsAg‐positive. About 71.4% had a diagnosis of biochemical reactivation [median (IQR) HBV DNA and ALT: 6.9 (5.4‐7.8) log IU/mL and 359 (102‐775) U/L]. Moreover, 10% of patients died from hepatic failure. Antiviral prophylaxis was documented in 57.9% and 15.7% of HBsAg‐positive and HBsAg‐negative patients at baseline‐screening (median [IQR] prophylaxis duration: 24[15‐33] and 25[17‐36] months, respectively). Notably, HBV reactivation occurred 2‐24 months after completing the recommended course of anti‐HBV prophylaxis in 35.3% of patients. By analysing treatment outcome, the cumulative probability of ALT normalization and of virological suppression was 97% and 69%, respectively. Nevertheless, in patients negative to HBsAg at baseline‐screening, only 27% returned to HBsAg‐negative status during prolonged follow‐up, suggesting the establishment of chronic infection. In conclusion, most patients received a diagnosis of HBV reactivation accompanied by high ALT and 10% died for hepatic failure, supporting the importance of strict monitoring for an early HBV reactivation diagnosis. Furthermore, HBV reactivation correlates with high risk of HBV chronicity in patients negative for HBsAg at baseline‐screening, converting a silent into a chronic infection, requiring long‐term antiviral treatment. Finally, a relevant proportion of patients experienced HBV reactivation after completing the recommended course of anti‐HBV prophylaxis, suggesting the need to reconsider proper duration of prophylaxis particularly in profound immunosuppression. [ABSTRACT FROM AUTHOR]

Objective: To assess the evidence for treatment of oral involvement of pemphigus and pemphigoid with biologics. Study Design: This systematic review used a comprehensive search strategy to identify literature describing oral involvement of pemphigus or pemphigoid treated with a biologic agent. The primary outcome measures were efficacy and safety of biologic therapy. Results: Inclusion criteria were met by 154 studies including over 1200 patients. Treatment of pemphigus with a total of 11 unique biologic agents and 3 unique combinations of agents is reported. Five randomized controlled trials (RCT) were included in the final analysis that investigated infliximab, IVIg, rituximab, and autologous platelet‐rich plasma therapy for pemphigus vulgaris. Three non‐RCT studies reported on successful rituximab or IVIg therapy for mucous membrane pemphigoid. Studies demonstrated considerable heterogeneity in agent, methods, and quality. Conclusions: Evidence clearly describing oral tissue response to biologic therapy is sparse. Two RCTs support use of rituximab, one supports use of IVIg, and one pilot study suggests intralesional injection of autologous platelet‐rich plasma aids healing of oral PV lesions. As oral lesions of pemphigus and pemphigoid can be refractory to systemic therapy, drug trials including biologic therapies should document details regarding response of the oral lesions to therapy. [ABSTRACT FROM AUTHOR]

Background: Despite effective therapies, outcomes for diffuse large B‐cell lymphoma (DLCBL) remain heterogeneous in older individuals due to comorbid diseases and variations in disease biology. Methods: Using the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database, the authors conducted a multistate survival analysis of 11,780 patients with DLBCL who were aged ≥65 years at the time of diagnosis (2002‐2009). Cox proportional hazards models were used to specify the impact of prognostic factors on overall survival and cause‐specific deaths, and the Aalen‐Johansen estimator was used to project the course of DLBCL over time with or without standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP). Results: Advanced age (hazard ratio [HR] for ages 71‐75 years: 1.25; HR for ages 76‐80 years: 1.46; HR for ages 81‐85 years: 1.88; and HR for age ≥86 years: 2.26), DLBCL stage (HR for Ann Arbor stage II: 1.28; HR for stage III: 1.54; and HR for stage IV: 1.95), Charlson Comorbidity Index (CCI) ≥1 (HR for CCI of 1, 1.15; and HR for CCI >1, 1.37), and not being married (HR, 1.12) were associated with an increased risk of DLBCL‐specific death. Being female (HR, 0.91) and of higher socioeconomic status (HR, 0.91) were associated with a lower risk of DLBCL‐related mortality after therapy. For patients treated with R‐CHOP (3610 patients), the risk of death due to DLBCL was 14.0% and 18.6%, respectively, at 2 and 5 years of treatment and plateaued afterward, confirming a 5‐year "cure" point while receiving R‐CHOP among older patients. Conclusions: Conducting a survival analysis over a large data set, the current study evaluated competing risks for death within a multistate modeling framework, and identified age, sex, and CCI as risk factors for DLBCL‐specific and other causes of death. Using a large data set and a multistate model, the current study evaluates competing risks for death in older individuals with diffuse large B‐cell lymphoma (DLBCL). After accounting for other factors, age, sex, and comorbidity appear to be risk factors for DLBCL‐related and other causes of death. [ABSTRACT FROM AUTHOR]

Summary: In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well‐tolerated in previously untreated patients with advanced‐stage, indolent non‐Hodgkin lymphoma (iNHL). After a median patient follow‐up of more than 108 months, we performed an intent‐to‐treat analysis of our 83 participants. Progression‐free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten‐year PFS rates for those with beta‐2‐microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10‐year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long‐term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10‐year follow‐up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL. [ABSTRACT FROM AUTHOR]

In multiple myeloma (MM), the synergy between immunomodulatory drugs (IMiDs) and monoclonal antibodies (MABs) has been demonstrated in several pivotal trials. However, disease refractory to either class of compounds remains a major therapeutic challenge. We here report on 3 heavily pretreated MM patients who were refractory to pomalidomide as well as to MABs against CD38 (daratumumab) or CD20 (rituximab), respectively, but who responded to retreatment with the same agents in combination. Responses were durable with PFS of 7, 10 (ongoing), and 30 months from initiation of combination treatment. The combination of IMiDs with MABs directed against MM cell surface antigens can overcome refractoriness to both agents. [ABSTRACT FROM AUTHOR]

The degree of somatic hypermutation, determined as percent deviation of immunoglobulin heavy chain gene variable region sequence from the germline ( IGHV%), is an important prognostic factor in chronic lymphocytic leukaemia ( CLL). Currently, a cut-off of 2% deviation or 98% sequence identity to germline in IGHV sequence is routinely used to dichotomize CLL patients into mutated and unmutated groups. Because dissimilar IGHV% cut-offs of 1-5% were identified in different studies, we wondered whether no cut-off should be applied and IGHV% treated as a continuous variable. We analysed the significance of IGHV% in 203 CLL patients enrolled on the original frontline fludarabine, cyclophosphamide and rituximab ( FCR) trial with a median of 10 years follow-up. Using the Cox Proportional Hazard model, IGHV% was identified as a continuous variable that is significantly associated with progression-free ( PFS) and overall survival ( OS) ( P < 0·001). Furthermore, we validated this finding in 323 patients treated with FCR off-protocol and in the total cohort ( n = 535). Multivariate analysis revealed a continuous trend. Higher IGHV% levels were incrementally associated with favorable PFS and OS in both FCR-treated cohorts ( P < 0·001, both cohorts). Taken together, our data suggest that IGHV% is a continuous variable in CLL patients treated with FCR. [ABSTRACT FROM AUTHOR]

Background Type B insulin resistance syndrome is a rare disease characterized by refractory transient hyperglycaemia and severe insulin resistance associated with circulating anti-insulin receptor antibodies. A standardized treatment regimen for type B insulin resistance syndrome has yet to be established. Case report We report the case of a 64-year-old man undergoing haemodialysis for antineutrophil cytoplasmic antibody-associated vasculitis and diabetic nephropathy, who developed rapid onset of hyperglycaemia (glycated albumin 52.1%). Type B insulin resistance syndrome was diagnosed, on the basis of positivity for anti-insulin receptor antibodies and the man's autoimmune history of antineutrophil cytoplasmic antibody-associated vasculitis and idiopathic thrombocytopenic purpura. Although severe hyperglycaemia persisted in spite of corticosteroids and high-dose insulin therapy, rituximab treatment resulted in remarkable improvement of the man's severe insulin resistance and disappearance of anti-insulin receptor antibodies without any adverse effects. Conclusions According to a literature review of 11 cases in addition to the present case, rituximab appears to be a safe and effective strategy for the treatment of corticosteroid-resistant type B insulin resistance syndrome. [ABSTRACT FROM AUTHOR]

The article presents a study which analyzed patients diagnosed with gray-zone lymphoma (GZL) at the University of Texas MD Anderson Cancer Center in Houston, Texas. Topics discussed include characteristics of patients with GZL, longer progression-free survival (PFS) found in patients with mediastinal GZL, and indication that dose-adjusted etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (DA-EPOCH-R) may improve outcome for patients with GZL.

The management of Waldenström macroglobulinaemia ( WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide ( DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88 WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate ( ORR) was 87%. The median progression-free survival ( PFS) and time-to-next-therapy ( TTNT) were 32 (95% confidence interval [ CI]: 15-51) and 50 (95% CI: 35-60) months, respectively. In the previously untreated cohort ( n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23-not reached [ NR]) and NR (95% CI: 37- NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients' MYD88 status. [ABSTRACT FROM AUTHOR]

Aims Rituximab is a monoclonal antibody directed against CD20, which is approved in rheumatoid arthritis (RA). This study aimed at assessing the influence of CD19+ cell counts as target-antigen amount, and of immunoglobulin G (IgG) serum concentrations on rituximab pharmacokinetics in RA patients. Methods In a cohort of 64 RA patients who had received repetitive courses of rituximab, the influence of CD19+ cell count, IgG serum concentration, body surface area, sex and disease activity score in 28 joints on rituximab pharmacokinetic parameters was assessed using a population pharmacokinetic analysis. Results A two-compartment model, with first-order distribution and elimination best described the data. The volume of distribution of central compartment and clearance of rituximab were estimated at 4.7 l and 0.56 l day-1, respectively. Distribution and elimination half-lives were 0.9 days and 17.3 days, respectively. As expected, the central volume of distribution increased with body surface area ( P = 0.012) and was higher in male than in female ( P = 0.004). We found that the elimination rate constant (k10) increased with CD19+ count ( P = 0.00022) and IgG concentration ( P = 7.4 × 10−8), and that k10 decreased with time ( P = 0.00015), partly explained by a change in target-antigen amount. Conclusions The association between CD19+ count and k10 may be explained by target-mediated drug disposition, while the association between IgG serum concentration and k10 may be explained by a saturation of the neonatal Fc receptor at high IgG concentrations, resulting in decreased recycling of rituximab. [ABSTRACT FROM AUTHOR]

The management of patients with immune thrombocytopenia ( ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid-sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high-grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins ( IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed. [ABSTRACT FROM AUTHOR]

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma ( nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option. [ABSTRACT FROM AUTHOR]

The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma ( BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose-Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array-based comparative genomic hybridization ( CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next-generation sequencing ( NGS). Ninety-seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy ( P = 0·038), shorter progression-free survival ( PFS; P = 0·007) and overall survival ( OS; P = 0·009). The integrative analysis of array- CGH and NGS showed that 26·3% (5/19) and 36·8% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS ( P = 0·011) while TCF3 alterations were associated with shorter OS ( P = 0·032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol. [ABSTRACT FROM AUTHOR]

Intensive chemotherapy regimens containing cytarabine have substantially improved remission durability and overall survival in younger adults with mantle cell lymphoma (MCL). However, there have been no long-term follow-up results for patients treated with these regimens. We present long-term survival outcomes from a pivotal phase II trial of rituximab, hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with methotrexate and cytarabine (R-HCVAD/MA). At 15 years of follow-up (median: 13·4 years), the median failure-free survival (FFS) and overall survival (OS) for all patients was 4·8 years and 10·7 years, respectively. The FFS seems to have plateaued after 10 years, with an estimated 15-year FFS of 30% in younger patients (≤65 years). Patients who achieved complete response (CR) after 2 cycles had a favourable median FFS of 8·8 years. Six patients developed myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) whilst in first CR. The 10-year cumulative incidence of MDS/AML of patients in first remission was 6·2% (95% confidence interval: 2·5-12·2%). In patients with newly diagnosed MCL, R-HCVAD/MA showed sustained efficacy, with a median OS exceeding 10 years in all patients and freedom from disease recurrence of nearly 15 years in almost one-third of the younger patients (≤65 years). [ABSTRACT FROM AUTHOR]

Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, has been shown to be active in newly diagnosed and relapsed patients with follicular lymphoma (FL), both as monotherapy and in combination with chemotherapy. Many studies suggest that the prognosis of patients with FL may improve when it is used in combination with chemotherapy. Despite these advances, the disease remains essentially incurable with standard therapy, and novel approaches to treatment are needed because optimal therapy is not defined. The combination of chlorambucil-rituximab is one of several standard treatment options for FL. Here, we considered data arising from 75 patients with newly diagnosed FL at the European Institute of Oncology treated with the combination of rituximab plus chlorambucil. The aim of this study was to evaluate the efficacy and safety of chlorambucil and rituximab, delivered 6 mg/m(2) /day orally for 6 weeks and 375 mg/m(2) in a standard 4-weekly schedule, respectively. Patients responding to the induction therapy received a prolonged therapy with four additional cycles of chlorambucil plus rituximab. Seventy-one patients (94.6%) completed the treatment; four patients discontinued treatment because of grade 3-4 hematological toxicity. The overall response rate was 97.3% including 74.7% of complete responses. Only two patients had a stable disease at revaluation after treatment. With a median follow-up of 57 months, 72 patients (96%) are alive. Median event-free survival (EFS) and median overall survival (OS) were not reached; 5-year OS rate was 98.4%. The 5-year EFS was 71.3%. By univariate and multivariate analyses, elevated beta-2 microglobulin levels and partial responses to therapy were correlated with worse EFS. These results suggest that the combination of chlorambucil and rituximab is an active and safe regimen in patients with newly diagnosed FL, principally in those with low tumour burden and favourable prognostic factors. [ABSTRACT FROM AUTHOR]

We describe three cases of relapsed hairy cell leukaemia (HCL) treated with pentostatin plus rituximab. All three achieved bone marrow complete remission but had persistent splenomegaly and hypersplenism. Because of the clinical uncertainty of its significance, they were all splenectomized. The spleen histology showed no evidence of HCL, but a five-fold thickening of the splenic capsule and areas of fibrosis in the red pulp. This process may have contributed to the lack of elasticity and caused the persistent splenomegaly. We discuss the clinical implications for future patient management. The three patients remain in remission at 1 +, 5 + and 9 + years. [ABSTRACT FROM AUTHOR]

Patients with chronic hepatitis B (HBsAg-positive) are at risk of viral reactivation if rituximab is administered without antiviral treatment, a potentially fatal complication of treatment. Patients with so-called 'resolved hepatitis B virus infection' (HBsAg-negative/cAb-positive) may also be at risk. We performed a systematic review of the English and Chinese language literature to estimate the risk of hepatitis B virus (HBV) reactivation in HBsAg-negative/cAb-positive patients receiving rituximab for lymphoma. A pooled risk estimate was calculated for HBV reactivation. The impact of HBsAb status and study design on reactivation rates was explored. Data from 578 patients in 15 studies were included. 'Clinical HBV reactivation', (ALT >3 × normal and either an increase in HBV DNA from baseline or HBsAg seroreversion), was estimated at 6.3% ( I2 = 63%, P = 0.006). Significant heterogeneity was detected. Reactivation rates were higher in prospective vs retrospective studies (14.2% vs 3.8%; OR = 4.39, 95% CI 0.83-23.28). Exploratory analyses found no effect of HBsAb status on reactivation risk (OR = 0.083; P = 0.151). Our meta-analysis confirms a measurable and potentially substantial risk of HBV reactivation in HBsAg-negative/cAb-positive patients exposed to rituximab. However, heterogeneity in the existing literature limits the generalizability of our findings. Large, prospective studies, with uniform definitions of HBV reactivation, are needed to clarify the risk of HBV reactivation in HBsAg-negative/cAb-positive patients. [ABSTRACT FROM AUTHOR]

The article discusses a study which evaluated the approach a surveillance following remission with first line therapy for diffuse large B cell lymphoma (DLBCL) in the rituximab era with clinical follow-up for at least 5 years with routine blood tests, including lactate dehydrogenase (LDH), without routine imaging. Topics covered include patient and treatment characteristics, the pattern of relapse detection, and the utility of routine blood tests to detect relapse.

Mantle cell lymphoma ( MCL) is essentially incurable with conventional chemotherapy. The MCL International Prognostic Index ( MIPI) is a validated specific prognostic index, but was derived from patients with advanced-stage disease primarily in the pre-rituximab era. We analysed 501 MCL patients (median age, 67 years; range 22-90) treated with rituximab-containing chemotherapy, and evaluated the prognostic factors adjusted by the treatment. Five-year overall survival ( OS) in the low, intermediate and high MIPI groups was 74%, 70% and 35%, respectively. Additional to MIPI risk factors, multivariate analysis revealed that low serum albumin and bone-marrow involvement were also significantly associated with a poor outcome. The revised- MIPI (R- MIPI) was constructed using six factors, namely age, performance status, white blood cell count, serum lactate dehydrogenase, bone-marrow involvement and serum albumin, which is divided into four prognostic groups. Five-year OS in low, low-intermediate (L-I), high-intermediate (H-I) and high R- MIPI groups was 92%, 75%, 61% and 19%, respectively. Hazard ratio for OS of L-I, H-I and high risk to low risk patients were 5·4, 8·3 and 33·0, respectively. R- MIPI, a new prognostic index with easy application to the general patient population, shows promise for identifying low- and high-risk MCL patients in the rituximab era. [ABSTRACT FROM AUTHOR]

This study systematically reviewed and meta-analysed the prognostic value of complete remission status at end-of-treatment 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). The systematic Pub- Med/MEDLINE search yielded seven suitable studies comprising a total of 737 R-CHOP-treated DLBCL patients who were in complete remission at end-of-treatment FDG-PET. Overall, the methodological quality of included studies was reasonable. The disease relapse rate among all patients with complete remission status according to end-of-treatment FDG-PET ranged from 7.0% to 20%, with a weighted summary proportion of 13.7%. Five of seven studies reported progression-free survival (PFS) of these patients at various specific time points, i.e., 2-year PFS (n = 1), estimated 3-year PFS (n = 3) and 5-year PFS (n = 1), which was 83%, 85-86.4% and 75%, respectively. Three of seven studies reported overall survival (OS) of these patients at various specific time points, i.e., estimated 3-year OS (n = 2) and estimated 5-year OS (n = 1), which were 90%, 93.6% and 83%, respectively. In conclusion, a non-negligible proportion of R-CHOP-treated DLBCL patients who achieve complete remission according to end-of-treatment FDG-PET experiences disease relapse during follow- up. [ABSTRACT FROM AUTHOR]

A persistently positive positron emission tomography ( PET) scan during therapy for diffuse large B-cell lymphoma ( DLBCL) is predictive of treatment failure. A response-adapted strategy consisting of an early treatment change to four cycles of R- ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after three cycles of R- CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET-positive patients received four cycles of R- ICE, PET-negative patients received two more cycles of R- CHOP. A ≥45% 2-year progression-free survival ( PFS) for mid-treatment PET-positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two-year PFS was 70%; 42% [90% confidence interval (CI), 19-63%] for PET-positives and 76% (90% CI 65-84%) for PET-negatives. Three-year overall survival ( OS) was 69% (90% CI 43-85%) and 93% (90% CI 86-97%) for PET-positive and -negative cases, respectively. The 2-year PFS for mid-treatment PET-positive patients intensified to R- ICE was 42%, with a wide confidence interval due to the low proportion of positive mid-treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials. [ABSTRACT FROM AUTHOR]

The primary objective of this prospective, randomized study was to compare the efficacy of a reduced regimen of only four doses of unpegylated filgrastim from day +8 to +11 per cycle with a standard once per cycle administration of pegylated filgrastim to maintain dose-intensity of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone given every 14 d) in previously untreated elderly patients with diffuse large B-cell lymphoma ( DLBCL). We included 51 patients (median age 66 years, range 60-76). Median dose intensity did not differ between the group of 24 patients receiving four doses of unpegylated filgrastim of each cycle (87·5%) and the group of 27 patients receiving pegylated filgrastim once per cycle on day 2 (89·4%) ( P = 0·9). There was also no difference in the frequency of adverse events, such as episodes of neutropenic fever and unplanned hospitalizations. Patient characteristics that negatively influenced dose intensity were reduced performance status, advanced stage disease and poor-risk International Prognostic Index, with Eastern Cooperative Oncology Group performance status ≥2 being the most significant factor. In conclusion, a limited support with 4 d of filgrastim appears to be equivalent to pegylated filgrastim administered once per cycle, and appears to be sufficient to maintain dose-intensity of the R-CHOP-14 regimen in elderly patients with DLBCL without risk factors. [ABSTRACT FROM AUTHOR]

Histone deacetylases ( HDACs) inhibitors are active in T-cell lymphoma and are undergoing pre-clinical and clinical testing in other neoplasms. Entinostat is an orally bioavailable class I HDAC inhibitor with a long half-life, which is under evaluation in haematological and solid tumour malignancies. To define the activity and biological effects of entinostat in B-cell lymphoma we studied its anti-tumour activity in several rituximab-sensitive or -resistant pre-clinical models. We demonstrated that entinostat is active in rituximab-sensitive cell lines ( RSCL), rituximab-resistant cell lines ( RRCL) and primary tumour cells isolated from lymphoma patients ( n = 36). Entinostat exposure decreased Bcl- XL ( BCL2L1) levels and induced apoptosis in cells. In RSCL and RRCL, entinostat induced p21 ( CDKN1A) expression leading to G1 cell cycle arrest and exhibited additive effects when combined with bortezomib or cytarabine. Caspase inhibition diminished entinostat activity in some primary tumour cells suggesting that entinostat has dual mechanisms-of-action. In addition, entinostat increased the expression of CD20 and adhesion molecules. Perhaps related to these effects, we observed a synergistic activity between entinostat and rituximab in a lymphoma-bearing severe combined immunodeficiency ( SCID) mouse model. Our data suggests that entinostat is an active HDAC inhibitor that potentiates rituximab activity in vivo and supports its further clinical development in B-cell lymphoma. [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disorder ( PTLD) remains a common complication of liver and bowel transplantion. The ubiquity of Epstein-Barr virus ( EBV) combined with engraftment of organs rich with lymphatic tissue and the requirement of highly immunosuppressive regimens are factors that account for the high frequency and poor prognosis of PTLD in this population. Early detection of the virus followed by pre-emptive reduction of immunosuppression are essential components in the management of PTLD, but can increase the risk of graft loss. More recently, the anti-CD20 monoclonal antibody (rituximab) has been shown to improve survival in various transplant populations with PTLD, while other therapeutic options, such as chemotherapy, surgery or radiotherapy, have minimal clinical impact. EBV-directed cytotoxic T cells have shown promise in the management of PTLD but clinical use is currently limited by lack of technical facilities worldwide. [ABSTRACT FROM AUTHOR]

The International Prognostic Index ( IPI) has been used for decades in diffuse large B-cell lymphoma ( DLBCL). A retrospective cancer registry analysis in North America showed significantly improved results when an enhanced IPI, the National Comprehensive Cancer Network ( NCCN)- IPI was applied. This novel score puts more weight on age and high levels of lactate dehydrogenase ( LDH). Nevertheless, it remains unclear if these results can be extrapolated to the general population. This retrospective bi-centre analysis included 499 unselected DLBCL patients who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and 2013. In our cohort, the NCCN- IPI was more accurate in identifying patients at low or high risk, despite older age, and more patients with increased LDH. Nevertheless, a modified scoring of the risk factors was required to more accurately identify elderly patients with a very favourable diagnosis, suggesting an impaired value of the original NCCN- IPI in the elderly. Serum β2-microglobulin and albumin were retained as independent prognostic factors for survival in a multivariate analysis. Our data confirm, for the first time, the superior prognostic power of the NCCN- IPI in an unselected, middle-European cohort. We furthermore propose a modified NCCN- IPI for more accurate prognostication in the elderly. Albumin and β2-microglobulin levels are likely to add significant information to the NCCN- IPI. [ABSTRACT FROM AUTHOR]

Relapsed aggressive lymphomas are often treated with platinum-based chemotherapy ( PBC) followed by an autologous stem cell transplant ( ASCT). Response rates to PBC in patients with relapsed aggressive lymphomas are c. 60%, and non-responders have a dismal prognosis. Novel therapies for aggressive lymphomas, including those failing PBC, are needed. We performed a phase II study of paclitaxel, topotecan and rituximab ( TTR) in patients with relapsed or refractory diffuse large B-cell, follicular grade IIIB, or transformed lymphomas, including those who previously failed PBC. The median age of the 72 patients enrolled was 54 years. Responding patients were offered ASCT after two courses. The overall response rate was 69% for all patients ( n = 49/71) and 45% for those who previously failed PBC ( n = 9/20). With a median follow up of 125 months for the censored observations, the overall survival ( OS) and progression-free survival at 5 years was 39% and 27%, respectively. Responding patients who received ASCT had an OS of 63% at 5 years. Our results demonstrate that TTR is an effective salvage regimen for patients with relapsed aggressive B-cell lymphomas, including those who previously failed PBC. Given the declining therapeutic outcomes of salvage PBC in the rituximab era, further evaluation of TTR is warranted. [ABSTRACT FROM AUTHOR]

The overall response rates and long-term survival of primary central nervous system lymphoma ( PCNSL) are still significantly inferior to the results achieved in similar subtypes of extranodal non- Hodgkin's lymphoma. It is clearly necessary to investigate new therapeutic methods on PCNSL. We encountered three patients histologically documented PCNSL as diffuse large B-cell lymphoma ( DLBCL). They were treated with R- IDARAM which comprised rituximab, idarubicin, dexamethasone, cytarabine and methotrexate. Patient 1 received stereotactic brachytherapy ( SBT) prior to chemotherapy performed with iodine-125 seeds (cumulative therapeutic dose 50 Gy). After six cycles of R- IDARAM at 3-weekly intervals, radiotherapy was applied at a dosage of 2000-4000 cGy in conventional schedule (180 or 200 cGy/day) to whole brain or spinal cord in all patients. Complete remission ( CR) was achieved after first two cycles of R- IDARAM in all patients. All three patients remained in CR at the time of this report with a median duration of follow-up of 23 months (ranging from 13 to 41 months). Three patients have been alive for 41, 13, 16 months respectively until now. The patient with the longest survival time was the one given SBT prior to chemotherapy. This study suggests that R- IDARAM combining with radiotherapy maybe a high effective regimen in PCNSL patients especially those with primary central nervous system DLBCL. A comprehensive treatment combining internal radiotherapy by SBT, modified R- IDARAM and followed reduced external radiotherapy may be a new treatment concept for PCNSL with higher efficiency and lower toxicity. [ABSTRACT FROM AUTHOR]

Follicular Lymphoma ( FL) is the second most common non-Hodgkin lymphoma ( NHL) subtype and its course is heterogeneous. At diagnosis, some patients with FL manifest a detectable leukaemic phase ( FL- LP), but this feature has been seldom described and is poorly characterized. Among 499 patients diagnosed with FL in Lyon-Sud hospital, 37 (7·4%) had characteristic FL- LP (by cytological blood smears and flow cytometric analysis). In addition, 91/1135 FL patients from the PRIMA study presented FL- LP at study entry. In order to evaluate the outcome of this Lyon-Sud cohort, FL- LP patients were matched with 111 newly diagnosed FL without LP according to the Follicular Lymphoma International Prognostic Index ( FLIPI) score, age and treatment. Presence of FL- LP was associated with shorter progression-free survival ( PFS) and overall survival ( OS) ( P = 0·004 and P = 0·031, respectively). Presence of FL- LP and high FLIPI score remained independent prognostic factors in a Cox model for time to progression ( TTP). A number of circulating lymphoma cells ( CLC) >4 × 109/l was the most significant predictor for a shorter TTP in this Cox model. The prognostic impact of FL- LP on TTP was validated in the PRIMA cohort ( P = 0·0004). In conclusion, FL- LP is a rare event associated with shorter PFS and patients with CLC >4 × 109/l have a poorer outcome. These patients should be monitored carefully to consider alternative therapeutic options. [ABSTRACT FROM AUTHOR]

Oral Diseases (2012) 18, 525-536 Biologic therapies are relatively innovative treatments aimed at modulating lymphocytes or cytokines. There are currently three broad classes of biologic therapies, tumour necrosis factor-alpha inhibitors, lymphocyte modulators and interleukin inhibitors; all are increasingly used in the treatment of inflammatory immune-mediated conditions, and several have potential applications in oral medicine. Guidelines for their use in licensed indications (e.g. rheumatoid arthritis, psoriasis, inflammatory bowel disease) include recommendations and guidance for patient selection and subsequent monitoring with discussion of potential adverse effects. An understanding of these is important when managing patients receiving biologic therapy for systemic disease, and compliance is essential in any use in oral medicine. Key aspects of current guidance are presented with particular emphasis on their relevance to clinicians working within oral and maxillofacial medicine/pathology/surgery and in specialist practice. [ABSTRACT FROM AUTHOR]

Juvenile dermatomyositis (JDM) is an autoimmune disease of the skin and muscle that affects children. The etiology is poorly understood, but genetic susceptibility, environmental triggers, and abnormal immune responses are each thought to play a part. T cells have traditionally been implicated in the immunopathogenesis of JDM, but dendritic cells, B cells, and microchimerism are increasingly associated. Additionally, myositis-specific autoantibodies (MSA) can be present in the sera of affected patients and may correlate with distinct clinical phenotypes. Given the role of humoral immunity and MSA, there has been recent interest in the use of rituximab to treat JDM. Early results are mixed, but it is hoped that a prospective clinical trial will shed light on the issue in the near future. [ABSTRACT FROM AUTHOR]

Rituximab is a monoclonal antibody directed against CD20, a pan B lymphocyte marker. It is approved in Australia for treatment of CD20-positive B cell non-Hodgkin lymphoma and rheumatoid arthritis. There is increasing off-label use of rituximab in conditions where B cells and autoantibodies play a role in the pathophysiology. Rituximab is not only expensive, but its safety in unregistered indications is uncertain. We performed a retrospective review of the off-label use of rituximab approved by the High Cost Drug Subcommittee at the Princess Alexandra Hospital between 2005 and 2008. Cases of post transplant lymphoproliferative disorder were excluded. A total of 28 patients received rituximab for a variety of off-label indications. There were no reported cases of serious infusion reactions or other notable adverse events. The most favourable outcomes were seen in myasthenia gravis, shrinking lung syndrome, thrombotic thrombocytopenic purpura, prevention and treatment of renal transplant rejection and lupus nephritis. No benefit was observed in cases of focal segmental glomerulosclerosis (primary or post-transplant recurrence) and post-transplant recurrence of haemolytic uremic syndrome. There was limited benefit in cryoglobulinaemic vasculitis. The cost of off-label use was in excess of $210 000. In the absence of formal clinical trials, decisions regarding off-label use of rituximab are difficult. Our cases contribute to the published literature and should help provide clinicians with greater insights into which conditions are likely to respond. As can be seen in our series, rituximab benefits people with certain conditions; longevity and cost-effectiveness are currently unknown. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic, autoimmune reaction-driven systemic inflammatory disease that affects joints and several other organs. Although anti-TNF therapy and combination therapy with traditional anti-rheumatic drugs have improved the treatment of RA, still quite a significant proportion of patients do not reach adequate anti-rheumatic response. The understanding of the pathogenesis of RA has developed markedly during the last two decades, and this has brought up new targets for anti-rheumatic therapy. B cells have been found to have a pivotal role in the development of arthritis both in experimental models and in humans. Rituximab, an anti-CD20 antibody that depletes B cells, has been introduced in the treatment of RA, and it has proven to be safe and efficacious in RA. This review gives an overview on the mechanism of action of rituximab in RA and summarizes the published clinical data of rituximab in the treatment of RA. [ABSTRACT FROM AUTHOR]

Many controlled clinical trials have proven that rituximab improves the clinical outcome of patients with mature B cell lymphoma. This study was conducted to assess the contribution of rituximab in the actual clinical practice. Patients with newly diagnosed mature B cell lymphoma treated at 20 National Hospital Organization hospitals from January 2000 to December 2004 were consecutively registered. Rituximab was approved in September 2002 for indolent B cell lymphoma and in September 2003 for aggressive B cell lymphoma in Japan. The patients were divided into two groups depending on whether they received induction therapy containing rituximab. The endpoint was to evaluate the rituximab benefit based on 2-year progression-free survival (PFS) and 2-year overall survival (OS). A total 1126 patients received chemotherapies. Of these, 762 were diagnosed as diffuse large B cell lymphoma (DLBCL) and 215 as follicular lymphoma (FL). PFS and OS were markedly improved in the rituximab group compared with the non-rituximab group in patients with DLBCL (both P < 0·001) and in patients with FL ( P < 0·001 and P = 0·003 respectively). Rituximab, when used for remission induction therapy, significantly improved the clinical outcome of the mature B cell lymphoma patient in actual clinical practice. [ABSTRACT FROM AUTHOR]

Oblimersen sodium plus rituximab was evaluated in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) patients. Oblimersen was administered as a continuous intravenous infusion at a daily dose of 3 mg/kg/d for 7 d on alternate weeks for 3 weeks. Rituximab was given at a weekly dose of 375 mg/m2 for six doses. Patients with stable disease or objective response were allowed to receive a second course of treatment. The overall response rate (ORR) was 42% with 10 complete responses (CR) and eight partial responses (PR). Twelve (28%) patients achieved a minimal response or stable disease. Among the 20 patients with follicular lymphoma the ORR was 60% (eight CR, four PR). Three of the responders were refractory to prior treatment with rituximab, and two of the responses occurred in patients who had failed an autologous stem cell transplant. Median duration of response was 12 months. Most toxicities were low grade and reversible. In conclusion, oblimersen sodium can be safely combined with rituximab. The combination appears to be most beneficial in patients with indolent NHL and warrants further investigation in a large randomized trial. [ABSTRACT FROM AUTHOR]

Immunochemotherapy with cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) is the standard treatment in non-immunosuppressed patients with diffuse large B-cell lymphoma (DLBCL), but its adequacy has not been definitively established in patients with human immunodeficiency virus (HIV)-related lymphoma. This phase II trial aimed to evaluate the safety and efficacy of six cycles of R-CHOP in patients with HIV-related DLBCL and to determine whether response to highly active antiretroviral therapy (HAART) had prognostic impact. Patients were eligible if they had performance status <3 and absence of active opportunistic infections. Eighty-one patients were enrolled, 57 in stages III or IV, International Prognostic Index (IPI) 0 or 1 ( n = 26), 2 ( n = 19), 3 ( n = 20) and 4 or 5 ( n = 16), and median CD4 lymphocyte count of 0·158 × 109/l. The main adverse events were neutropenia (48% of cycles) and infections (10% of cycles), which were fatal in seven patients. Complete response was achieved in 55 (69%) patients, with an estimated 3-year disease-free survival of 77% and 3-year overall survival of 56%. IPI score and virological response to HAART were the prognostic parameters for response and survival. In HIV-related DLBCL R-CHOP is feasible, safe and effective. The prognosis depends on lymphoma-related parameters and on the response to HAART. [ABSTRACT FROM AUTHOR]

Background Patients with chronic immune thrombocytopenic purpura (ITP) only require treatment if they are bleeding, or prior to scheduled operations. Patients are also treated if platelet counts are very low. Some patients become refractory, relapse or do not respond to treatment with steroids. Splenectomy is effective in raising the platelet count in most patients, but as spontaneous remission may occur even after 1 year or more, it is justified to defer splenectomy. Furthermore, splenectomy and/or first-line treatment modalities may not suit all patients. Therefore, alternatives are desirable. Materials This review will focus on anti-B cell therapy with rituximab, and two thrombopoietin mimetic agents that have entered clinical trials, AMG 531 and eltrombopag. These therapeutics have been studied in patients who were refractory to first-line treatment and/or splenectomy, and to defer splenectomy. Results There are no controlled trials with rituximab, but clinical experience has shown a success rate of 40% to 60%. Encouraging phase 1 and 2 data have been published for both thrombopoietin mimetics; preliminary data from an open-label extension trial with AMG 531 and from phase 3 studies with eltrombopag further confirm their efficacy. Conclusion Clinical experience will ultimately determine the appropriate indications of these new treatments for ITP. [ABSTRACT FROM AUTHOR]

Reports on the case of a pediatric patient with relapsed refractory autoimmune hemolytic anemia. Medical history of the patient; Outcome of treatments with rituximab or anti-CD20 antigen therapy; Recommendation to prevent opportunistic infections.