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Rituximab
Kinds of Rituximab Terms modified by Rituximab Selected AbstractsUse of rituximab to treat refractory Diamond-Blackfan anemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2005Akira Morimoto Abstract:, We report here the first case with Diamond-Blackfan anemia (DBA) who responded to rituximab. The patient is an 8-yr-old Japanese girl with refractory DBA accompanied by complex congenital heart disease. She received two doses of rituximab, 375 mg/m2/wk. She became transfusion independent 6 months after the treatment without any serious side effect. However, after 8 months of transfusion-free period, her condition returned to the pretreatment level with recovery of peripheral B cells. Rituximab may be a successful therapy for refractory DBA where B cells play a crucial role in the pathogenesis of the severe anemia. [source] Rituximab in advanced rheumatoid arthritisFUTURE PRESCRIBER, Issue 2 2006Michael Guida BSc Rheumatoid arthritis (RA) continues to have a major impact on public health. Costs to the individual and to the NHS are high, and treatment options for RA are by no means perfect. This article reviews rituximab, an agent that interrupts inflammatory events via a novel mode of action, and shows promise as a new intervention in cases of moderate to severe RA. Copyright © 2006 John Wiley & Sons, Ltd. [source] Rituximab for congenital haemophiliacs with inhibitors: a Canadian experienceHAEMOPHILIA, Issue 1 2006M. CARCAO Summary., When a high titre inhibitor develops in a patient with haemophilia, attempts are made to eradicate it through immune tolerance induction therapy (ITI) involving the frequent and regular administration of factor, usually for months to years. ITI is successful in only two thirds of patients prompting investigators to explore alternate regimens to use in haemophiliacs failing conventional ITI. Rituximab is an anti-CD20 monoclonal antibody, which has shown promise in the treatment of B-cell-mediated disorders. We developed a protocol for the use of rituximab in haemophilia A (HA) patients failing conventional ITI or in those haemophiliacs where the likelihood of success of conventional ITI is poor. Patients receive 375 mg m,2 of intravenous rituximab weekly for 4 weeks followed by monthly (up to 5 months) until inhibitor disappearance and establishment of normal FVIII pharmacokinetics (recovery and half-life). Patients are concurrently placed on recombinant FVIII (100 U kg,1 day,1). We have placed five haemophiliacs (four children with severe HA, and one adult with mild HA) on this protocol. In three patients (two with severe HA and one with mild HA) inhibitors disappeared although in neither severe haemophiliac did FVIII pharmacokinetics completely normalize. The fourth patient had a significant drop in inhibitor titres although not a complete disappearance of the inhibitor. All four of these patients ceased bleeding following rituximab. The fifth patient had no response to rituximab. This non-responding patient was not placed on concurrent FVIII. Our five cases suggest that rituximab may hold promise in the eradication of inhibitors. Prospective randomized studies are required to determine the value of this agent in inhibitor management. [source] Evaluation of the off-label usage of rituximab in a large teaching hospital in New South WalesINTERNAL MEDICINE JOURNAL, Issue 8 2007R. Sharma Abstract A retrospective review of patients receiving rituximab off label in a large teaching hospital was conducted between July 2002 and January 2006. The indication, dosing regimen, efficacy and cost of rituximab were evaluated. Rituximab was prescribed for three clinical indications; acute organ transplant rejection, post-transplant lymphoproliferative disease and autoimmune disease. On average, 600 mg of rituximab was prescribed weekly for 4 weeks, costing the hospital $108 739.37. We suggest an initial approval for a limited number of doses with subsequent approval dependent on improvement in predefined clinical or biochemical end-points. Furthermore, we suggest an Australia-wide central database be established to enable delineation of the optimal dosing schedule, as well as monitoring of clinical outcome. [source] Rituximab: Applications in dermatologyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2006Mitra M. Fatourechi Rituximab is a chimeric anti-CD20 monoclonal antibody which has been used extensively for B-lymphocytic malignancies. In addition, applications for autoimmune diseases have emerged in recent years. Case reports support the use of rituximab in certain dermatologic conditions, including paraneoplastic pemphigus, pemphigus vulgaris, graft versus host disease, and cutaneous B-cell malignancies. Clinical trials are lacking and would be an appropriate next step. [source] Berend Houwen Memorial Lecture: ISLH Las Vegas May 2009INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2009The pathogenesis, management of thrombotic microangiopathies Summary Thrombotic microangiopathies are a relatively rare group of congenital and inherited disorders caused by defects in processing the ultra large forms of von Willibrand factor which pathologically give rise to platelet rich microthrombi in the micro arterial circulation leading to end organ damage particularly in the brain, heart and kidneys. Identification of the ADAMTS 13 gene has led to the definition of congenital deficiency of its activity or failure of activity due to the development of an inhibitory IgG antibody. The idiopathic autoimmune form of the disease is the most common. There are various subgroups of acquired TTP associated with HIV infection, pregnancy, pancreatitis, associated with bone marrow transplantation, various disseminated malignancies and certain drugs, particularly Clopidogrel. Diagnostic assays are now becoming widely available to identify ADAMTS 13 activity and also acquired antibodies to the enzyme. Mainline treatment is associated with daily plasma exchange with associated other immunosuppressant treatments particularly steroids and recently the use of Rituximab, a monoclonal anti-CD20 antibody. Despite improvement in treatment modalities there is still significant mortality of 10,20%, particularly if there is a delay in initiating plasma exchange. Relapse also occurs in 20,50% of patients although this may be improved by Rituximab therapy. [source] A case of refractory vasculitic ulcers in a systemic lupus erythematosus patient responding to rituximab and hyperbaric oxygen therapyINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2009Nai-Lee LUI Abstract Large refractory vasculitic ulcers are not commonly seen in systemic lupus erythematosus (SLE) patients. We report a case of refractory vasculitic ulcers responding to rituximab, a monoclonal antibody directed against CD20 cells leading to prolonged B cell depletion. This treatment was initiated after treatment with high-dose steroids and other immunosuppressants were ineffective/associated with significant side-effects. Following treatment with rituximab, there was sustained clinical improvement and subsequent reduction of prednisolone dose. Rituximab was well-tolerated. Concomitant methotrexate therapy and hyperbaric oxygen therapy (HBOT) may have aided the recovery of the patient's vasculitic ulcers. This case and anecdotal reports have illustrated the efficacy and safety of rituximab in the treatment of refractory SLE-related vasculitic ulcers. Further studies to determine the long-term efficacy and side-effects would be useful. [source] Rituximab as an adjunct to plasma exchange in TTP: A report of 12 cases and review of literature,JOURNAL OF CLINICAL APHERESIS, Issue 5 2008Sushama Jasti Abstract Idiopathic thrombotic thrombocytopenic purpura (TTP) is caused by the production of autoantibodies against the Von Willebrand factor cleaving enzyme. This provides a rationale for the use of rituximab in this disease. We report a retrospective review of 12 patients treated with rituximab for TTP refractory to plasma exchange. Eleven patients were treated during initial presentation, and one patient was treated for recurrent relapse. Ten patients responded to treatment. Median time to response after first dose of rituximab was 10 days (5,32). Of the 11 patients treated during initial presentation, nine remain free of relapse after a median follow-up of 57+ months (1+,79+). Two patients died during initial treatment. One patient was lost to follow-up 1 month after achieving complete response. The patient treated for recurrent disease during second relapse remained disease free for 2years, relapsed and was treated again with rituximab, and was in remission for 22 months. She relapsed again, was retreated, and has now been in remission for 21+ months. We conclude that rituximab is an useful addition to plasma exchange treatment in TTP, but its exact role and dosing need to be verified in prospective studies. J. Clin. Apheresis, 2008. © 2008 Wiley-Liss, Inc. [source] Rituximab as an effective treatment of hyperhemolysis syndrome in sickle cell anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Claude Bachmeyer No abstract is available for this article. [source] Synergistic antitumor effects of lenalidomide and rituximab on mantle cell lymphoma in vitro and in vivo,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2009Liang Zhang Rituximab (RTX), a chimeric anti-CD20 antibody, is associated with direct induction of apoptosis and antibody-dependent cell-mediated cytotoxicity (ADCC) with clinical efficacy in mantle cell lymphoma (MCL). Lenalidomide (LEN), a novel immunomodulatory agent, sensitizes tumor cells and enhances ADCC. Our study attempted to elucidate the mechanism of LEN-enhanced RTX-mediated cytotoxicity of MCL cells. We found that LEN and RTX induced growth inhibition of both cultured and fresh primary MCL cells. LEN enhanced RTX-induced apoptosis via upregulating phosphorylation of c-Jun N-terminal protein kinases (JNK), Bcl-2, Bad; increasing release of cytochrome-c; enhancing activation of caspase-3, -8, -9 and cleavage of PARP. Meanwhile, LEN activated NK cells and increased CD16 expression on CD56lowCD16+ NK cells. Whole PBMCs but not NK cell-depleted PBMCs treated with LEN augmented 30% of RTX-dependent cytotoxicity. Daily treatment with LEN increased NK cells by 10-folds in SCID mice, and combination of LEN and RTX decreased tumor burden and prolonged survival of MCL-bearing SCID mice. Taken together, our study demonstrates that LEN plus RTX provides a synergistically therapeutic effect on MCL cells by enhancing apoptosis and RTX-dependent NK cell-mediated cytotoxicity and may be an optimal combination in the clinical trial of relapsed or refractory MCL. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Rituximab in a child with relapsed Burkitt lymphoma,PEDIATRIC BLOOD & CANCER, Issue 2 2007Ali Bay MD No abstract is available for this article. [source] Generalized Erythrodermic Pemphigus Foliaceus in a Child and Its Successful Response to Rituximab TreatmentPEDIATRIC DERMATOLOGY, Issue 2 2007Elizabeth Alvarez Connelly M.D. The nonendemic or sporadic form of this entity is rare in children and typically presents with a milder, more localized rash that usually follows a benign course of short duration. We describe an affected patient atypical in both her young age and the severity of skin findings. Our patient presented with a full body exfoliative erythroderma at 21 months of age. After an extensive work-up to determine the etiology of her exfoliative erythroderma, direct and indirect immunofluorescence studies confirmed the diagnosis of pemphigus foliaceus. Rituximab therapy was initiated based on the patient's refractory disease course to multiple immunosuppressive agents. Rituximab is a therapeutic monoclonal antibody targeting CD20, an integral membrane protein highly expressed on the surface of pre-B lymphocytes and activated mature B lymphocytes. The patient's skin exhibited marked clinical improvement after the start of rituximab infusions over 12 weeks. Her initial desmoglein 1 antibody level was greater than 1:1280, which decreased to 1:16 after seven rituximab treatments. She has had no skin flares since initiating treatment with rituximab therapy. Based on this clinical and serologic response, the use of rituximab may be helpful in the treatment of pediatric pemphigus foliaceus refractory to mainstays of therapy. [source] Successful Treatment of Refractory Childhood Pemphgus Vulgaris with Anti-CD20 Monoclonal Antibody (Rituximab)PEDIATRIC DERMATOLOGY, Issue 5 2005Heidi H. Kong M.D. Immunosuppressive treatment can be challenging. Rituximab (anti-CD20 monoclonal antibody) has been used to treat autoimmune disorders by depletion of CD20 B cells. Successful rituximab therapy has been reported in adults with refractory pemphigus vulgaris. We present a girl with childhood pemphigus vulgaris unresponsive to treatment with azathioprine, mycophenolate mofetil, plasmapheresis, and intravenous immunoglobulin with systemic prednisone who responded to treatment with rituximab. She had a corresponding decline in circulating antibodies against desmoglein 1 and 3 and a decline in diphtheria and tetanus-specific antibody titers. [source] Late-onset neutropenia following RCHOP chemotherapy in diffuse large B-cell lymphoma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2009Gillianne Geet Yi Lai Rituximab has been associated with the development of late-onset neutropenia (LON). As only heterogeneous studies have been conducted, its incidence and clinical course remain unclear. We aim to: (1) study the incidence and clinical relevance of WHO grade 3/4 LON in a uniform group of patients with diffuse large B-cell lymphoma (DLBCL) in complete remission following curative rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) chemotherapy; (2) ascertain predictive factors for LON. The 121 eligible patients identified from our prospectively maintained database were followed up for occurrence of WHO grade 3/4 LON. The clinical course of LON was documented, and its relationship with patient- and tumor-related factors was analyzed. With a median follow-up of 883 days (range, 265,1762), 13.2% had developed LON of grade 3/4. The median time to neutrophil nadir was 129 days (range, 39,277). The median time to recovery was 69 days (range, 3,349) and occurred in all except two patients. Only one episode of nonlife threatening bacterial culture-positive urinary tract infection and pulmonary tuberculosis, both occurring in the same patient was documented. Results of Fischer's exact test revealed that age, stage, LDH level, ECOG, marrow involvement, and hematologic parameters did not predict for LON development. WHO grade 3/4 LON is not infrequent in patients with DLBCL receiving RCHOP. Even so, it is reassuring that LON is self-limiting and unassociated with life-threatening infection. A watchful waiting approach is appropriate in majority of patients who develop LON following RCHOP. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Rituximab (B-cell depleting antibody) associated lung injury (RALI): A pediatric case and systematic review of the literaturePEDIATRIC PULMONOLOGY, Issue 9 2009Martin Bitzan MD Abstract Introduction Pulmonary toxicity of delayed onset is a rare complication of B-lymphocyte depleting antibody therapy and has been almost exclusively reported in older patients with B-cell malignancies. Aims To describe a pediatric patient with rituximab-associated lung injury (RALI), to systematically analyze previous reports of pulmonary complications, and to summarize common clinico-pathological features, treatment, and outcome. Results A teenage boy with focal segmental glomerulosclerosis (FSGS) presented with progressive dyspnea, fever, hypoxemia and fatigue 18 days after the completion of a second course of rituximab infusions for calcineurin inhibitor-dependent nephrotic syndrome. Respiratory symptoms started while he received high-dose prednisone for persistent proteinuria. Bilateral, diffuse ground-glass infiltrates corresponded to the presence of inflammatory cells in the bronchioalveolar lavage fluid. Empiric antibiotic treatment including clarithromycin was given, but the microbiological work-up remained negative. Serum IgE, C3, and C4 concentrations were normal. He recovered within 3 weeks after onset. We systematically reviewed 23 reports describing 30 additional cases of rituximab-associated lung disease. Twenty eight patients had received rituximab for B-cell malignancies, one for graft-versus-host disease and one for immune thrombocytopenia. Median age was 64 years (interquartile range [IQR] 58,69 years). Seventy one percent received concomitant chemotherapy. Time to onset from the last rituximab dose was 14 days (IQR 11,22 days). Eleven of 31 patients required mechanical ventilation, and 9 died (29%). Ventilation was a significant predictor of fatal outcome (odds ratio 46.7; confidence interval 9.5,229.9). High dose glucocorticoid therapy did not improve survival or prevent severe lung disease or death. Conclusions With the expanding use of rituximab for novel indications, additional cases of RALI affecting younger age groups are expected to emerge. Mechanical ventilation predicts poor outcome. Glucocorticoids may not be protective. Pediatr Pulmonol. 2009; 44:922,934. © 2009 Wiley-Liss, Inc. [source] Rituximab for the treatment of post-bone marrow transplantation refractory hemolytic anemia in a child with Omenn's syndromePEDIATRIC TRANSPLANTATION, Issue 5 2007Briuglia Silvana Abstract:, Omenn's syndrome is a rare severe combined immunodeficiency that kills affected subjects before the end of the first year of life unless patients are treated with bone marrow transplantation (BMT). Unfortunately, post-BMT patients may develop autoimmune diseases, such as autoimmune hemolytic anemia (AIHA), which sometimes fails to respond to standard therapies. Rituximab is a chimeric, human, immunoglobulin G1/k monoclonal antibody specific for the CD20 antigen expressed on the surface of B lymphocytes. Rituximab is currently only labeled for treatment of B-cell lymphoproliferative disorders, such as B-cell non-Hodgkin's lymphoma and follicular lymphoma; however, it is also employed in the treatment of a variety of disorders mediated by auto-antibodies, such as AIHA and transplant-related autoimmune disorders. Herein, we describe the case of a 23-month-old male child with Omenn's syndrome, who had undergone BMT and was successfully treated with rituximab (375 mg/m2 intravenously, weekly for three times) for refractory post-BMT hemolytic anemia. Our findings evidence that rituximab should be considered for treatment of post-BMT AIHA refractory to traditional therapy also in children with primary immunodeficiencies; furthermore, rituximab might represent a means to obtain remissions without the toxic effects associated with corticosteroid and immunosuppressive agents. [source] Rituximab is effective for human herpesvirus-8-negative primary effusion lymphoma with CD20 phenotype associated hepatitis C virus-related liver cirrhosisAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2004Toshitatsu Takao No abstract is available for this article. [source] Response of myasthenia gravis to rituximab in a patient with non-Hodgkin lymphomaAMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2004Ajeet Gajra Abstract Myasthenia gravis is a B-cell-mediated autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles. The underlying defect is an autoantibody-mediated attack on the acetylcholine receptors (AchRs) at the neuromuscular junction. Rituximab is a genetically engineered chimeric murine/human monoclonal antibody indicated for treatment of patients with low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma. Based on its potential for elimination of auto-reactive B-cell clones, rituximab may have a role in the management of some autoimmune disorders. We report a patient with B-cell, follicular non-Hodgkin lymphoma and a long-standing history of myasthenia gravis and the favorable impact of rituximab on both disorders. Am. J. Hematol. 77:196,197, 2004. © 2004 Wiley-Liss, Inc. [source] Rituximab: first monoclonal antibody for severe, active RAPRESCRIBER, Issue 12 2007Article first published online: 4 OCT 200 Rituximab (MabThera) is a monoclonal antibody that exerts a novel anti-inflammatory action in rheumatoid arthritis via B-cell depletion. In our New products review Michael Guida presents the clinical data relating to its efficacy and adverse effects, and Dr Michael Plant comments on its place in therapy. Copyright © 2007 Wiley Interface Ltd [source] Analysis of immunoglobulin glycosylation by LC-ESI-MS of glycopeptides and oligosaccharidesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 14 2008Johannes Stadlmann Abstract Two LC-ESI-MS methods for the analysis of antibody glycosylation are presented. In the first approach, tryptic glycopeptides are separated by RP chromatography and analyzed by ESI-MS. This "glycopeptide strategy" allows a protein- and subclass-specific quantitation of both neutral and sialylated glycan structures. Additional information about under- or deglycosylation and the protein backbone, e.g., termini, can be extracted from the same data. In the second LC-ESI-MS method, released oligosaccharides are separated on porous graphitic carbon (PGC). A complete structural assignment of neutral and sialylated oligosaccharides occurring on antibodies is thereby achieved in one chromatographic run. The two methods were applied to polyclonal human IgG, to commercial mAb expressed in CHO cells (Rituximab, Xolair, and Herceptin), in SP2/0 (Erbitux and Remicade) or NS0 cells (Zenapax) and the anti-HIV antibody 4E10 produced either in CHO cells or in a human cell line. Both methods require comparably little sample preparation and can be applied to SDS-PAGE bands. They both outperform non-MS methods in terms of reliability of peak assignment and MALDI-MS of underivatized glycans with regard to the recording of sialylated structures. Regarding fast and yet detailed structural assignment, LC-MS on graphitic carbon supersedes all other current methods. [source] Low-Dose Rituximab for Posttransplant Recurrent Membranous NephropathyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010P. Cravedi No abstract is available for this article. [source] Is Rituximab Safe to Use in Kidney Transplant Patients?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010S. C. Jordan Rituximab is an emerging therapeutic agent in transplantation, but concerns remain over proof of efficacy, safety and dosing. See article by Kamar et al on page 89. [source] Successful Renal Transplantation in Factor H Autoantibody Associated HUS with CFHR1 and 3 Deficiency and CFH Variant G2850TAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010A. M. Waters Factor H (CFH) autoantibodies are associated with atypical hemolytic uremic syndrome (aHUS). Peritransplantation plasma exchange therapy and intensification of immunosuppression, with adjuvant use of anti-CD20 monoclonal antibodies has recently been advocated for cases of CFH-autoantibody associated aHUS. In this report, we describe successful deceased donor renal transplantation in a case of CFH-autoantibody associated aHUS with combined CFHR1 and 3 deficiency in addition to the CFH sequence variant, (cG2850T, pGln950His). CFH-autoantibodies were detected 2 weeks prior to transplantation. Disease recurrence was not observed using basiliximab, an IL2-receptor antagonist and high-dose corticosteroids with mycophenolate mofetil. Adjuvant therapies such as Rituximab nor intensification of plasma therapy were employed. Consequently, careful consideration needs to be given to the use of additional immunosuppression in certain cases of CFH-autoantibody associated aHUS. Serial measurement of CFH-autoantibodies is required in the immediate pre- and posttransplantation period to further clarify their role as a factor in the recurrence of aHUS posttransplantation. Furthermore, delineation of the functional significance of CFH-autoantibodies is warranted in individual cases. [source] Recurrent Idiopathic Membranous Nephropathy: Early Diagnosis by Protocol Biopsies and Treatment with Anti-CD20 Monoclonal AntibodiesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009Ziad M. El-Zoghby Membranous nephropathy (MN) recurs posttransplant in 42% of patients. We compared MN recurrence rates in a historical cohort transplanted between 1990 and 1999 and in a current cohort diagnosed by protocol biopsies, we analyzed the progression of the disease and we assessed the effects of anti-CD20 antibodies (Rituximab) on recurrent MN. The incidence of recurrent MN was similar in the historical (53%) and the current cohorts (41%), although in the later the diagnosis was made earlier (median, 4[2,21] months vs. 83[6,149], p = 0.002) and the disease was clinically milder. Twelve out of 14 patients (86%) with recurrent MN in the current cohort had progressive increases in proteinuria. Eight recipients were treated with Rituximab after their proteinuria increased from median, 211 mg/day (64,4898) at diagnosis to 4489 (898,13 855) (p = 0.038). Twelve months post-Rituximab, 75% of patients had either partial (PR) or complete remission (CR). After 24 months 6/7 (86%) had PR/CR and one patient relapsed. Posttreatment biopsies showed resorption of electron dense immune deposits in 6/7 cases and were negative for C3 (4/7) and IgG (3/7). Protocol biopsies allow early diagnosis of subclinical recurrent MN, which is often progressive. Treatment of recurrent MN with Rituximab is promising and should be evaluated in a prospective randomized controlled trial. [source] Treatment of PTLD with Rituximab and CHOP Reduces the Risk of Renal Graft Impairment after Reduction of ImmunosuppressionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009R. Trappe We addressed the effect of post-transplant lymphoproliferative disorder (PTLD) treatment with rituximab monotherapy or CHOP-based chemotherapy (± rituximab) after upfront immunosuppression reduction (IR) on renal graft function in a longitudinal analysis of 58 renal transplant recipients with PTLD and 610 renal transplant controls. Changes in the estimated glomerular filtration rate over time were calculated from a total of 6933 creatinine measurements over a period of >1 year using a linear mixed model with random and fixed effects. Renal graft function significantly improved with treatment of PTLD, especially in the chemotherapy subgroup. Patients treated with IR+chemotherapy ± rituximab had a noninferior graft function compared with untreated controls suggesting that the negative impact of IR on the renal graft function can be fully compensated by the immunosuppressive effect of CHOP. The immunosuppressive effect of single agent rituximab may partially compensate the negative impact of IR on the graft function. Thus, it is possible to reduce immunosuppression when using chemotherapy to treat PTLD. [source] Evidence for Humoral Rejection of a Pancreatic Islet Graft and Rescue with Rituximab and IV Immunoglobulin TherapyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009L. Kessler We describe the decline in islet function, in relation to HLA sensitization, in an islet transplant recipient and the recovery of this function after treatment with anti-CD20 monoclonal antibody and IV immunoglobulins. A 51-year-old woman with type 1 diabetes received one intraportal islet infusion. Following this transplantation, she became insulin independent. A search for HLA antibodies by using an ELISA technique remained consistently negative for HLA class I and II. It was only 2 years after the islet transplantation that this search became positive against class II antigens, reaching a peak of reactivity concomitantly with the appearance of a deterioration of glucose control requiring low-dose insulin therapy. Luminex® screening and single-antigen assays then revealed the presence of both nondonor-specific and donor-specific antibodies against HLA class II molecules. This immunization, already present in the pretransplant serum, had increased during the 6 months preceding the clinical deterioration. Since these data nevertheless pointed to antibody-mediated rejection of the islet allograft, treatment with anti-CD20 monoclonal antibody and IV immunoglobulins was initiated. One month later, the search by ELISA for antibodies against HLA class II antigens became negative, the Luminex® tests normalizing more gradually. As the result of an improvement in glucose control, the patient was again insulin-free. [source] A Randomized, Prospective Trial of Rituximab for Acute Rejection in Pediatric Renal TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2008V. Zarkhin We report 1-year outcomes of a randomized study of Rituximab versus standard-of-care immunosuppression (Thymoglobulin and/or pulse steroids) for treatment of biopsy confirmed, acute transplant rejection with B-cell infiltrates, in 20 consecutive recipients (2,23 years). Graft biopsies, with Banff and CADI scores, CD20 and C4d stains, were performed at rejection and 1 and 6 months later. Peripheral blood CMV, EBV and BK viral loads, graft function, DSA, immunoglobulins, serum humanized antichimeric antibody (HACA) and Rituximab, and lymphocyte counts were monitored until 1 year posttreatment. Rituximab infusions were given with a high index of safety without HACA development and increased infections complications. Rituximab therapy resulted in complete tissue B-cell depletion and rapid peripheral B-cell depletion. Peripheral CD19 cells recovered at a mean time of ,12 months. There were some benefits for the recovery of graft function (p = 0.026) and improvement of biopsy rejection scores at both the 1- (p = 0.0003) and 6-month (p < 0.0001) follow-up biopsies. Reappearance of C4d deposition was not seen on follow-up biopsies after Rituximab therapy, but was seen in 30% of control patients. There was no change in DSA in either group, independent of rejection resolution. This study reports safety and suggests further investigation of Rituximab as an adjunctive treatment for B-cell-mediated graft rejection. [source] Analysis of Subcutaneous (SQ) Alemtuzumab Induction Therapy in Highly Sensitized Patients Desensitized With IVIG and RituximabAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2008A. A. Vo Here we report on our experience with subcutaneous (SQ) Alemtuzumab in an uncontrolled study in highly HLA-sensitized patients (HS). From 3/05,4/07, 54 HS patients received Alemtuzumab 30 mg SQ as induction. Patient and graft survival, AR episodes, serum creatinines, absolute lymphocyte counts, monthly PCR monitoring for viruses, AE/SAEs and infectious complications were monitored. No patient to date has developed acute injection-related reactions after SQ Alemtuzumab; however, bone marrow suppression was occasionally seen requiring reduction or elimination of mycophenolate mofetil approximately 1,2 months posttransplant. Patient and graft survival at 12 M was 98%/96%, respectively. AR episodes occurred in 35% with 20% being C4d+ AMR. Mean SCrs at 12 M were 1.4 ± 0.3 mg/dL. The nadir ALC was 0.17 ± 0.19 within 24 h and sustained up to 365 days posttransplant. Infections occurred in eight patients (five with polyoma BK viremia [PBK], one CMV/PBK and two CMV viremia). SQ Alemtuzumab was well tolerated and resulted in prolonged lymphocyte depletion. Compared to our previous experience with daclizumab and rabbit ATG induction in HS patients, single-dose SQ Alemtuzumab was more cost effective, showed similar infection rates and did not reduce the AMR rates posttransplant. Although uncontrolled, these observations suggest that induction therapy with Alemtuzumab appears feasible and indeed promising, but awaits more definitive study. [source] Successful Induction of Remission With Rituximab for Relapse of ANCA-Associated Vasculitis Post-Kidney Transplant: Report of Two CasesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007D. Geetha Kidney transplantation should be considered the treatment of choice for patients with end-stage renal disease due to antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). However, relapses of AAV have been reported to occur in 9,40% of cases following kidney transplantation and may adversely affect allograft outcome. These relapses are usually treated with cyclophosphamide (CYC) and glucocorticoids, but the repeated use of CYC carries a risk of substantial toxicity that may limit or prohibit its use in some patients. B lymphocytes have been implicated in the pathogenesis of AAV, and their depletion has been effective as salvage therapy for refractory disease in the nontransplant setting. We report the successful induction of remission using rituximab in two patients who suffered relapse of AAV post-kidney transplant. Given the substantial morbidity and adverse effects of CYC, rituximab appears to be a suitable alternative agent to treat relapses of AAV posttransplantation. [source] Treatment of PTLD with Rituximab or ChemotherapyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2006R.L. Elstrom Information regarding treatment of post-transplant lymphoproliferative disease (PTLD) beyond reduction in immunosuppression (RI) is limited. We retrospectively evaluated patients receiving rituximab and/or chemotherapy for PTLD for response, time to treatment failure (TTF) and overall survival (OS). Thirty-five patients met inclusion criteria. Twenty-two underwent rituximab treatment, with overall response rate (ORR) 68%. Median TTF was not reached at 19 months and estimated OS was 31 months. In univariable analysis, Epstein-Barr virus (EBV) positivity predicted response and TTF. LDH elevation predicted shorter OS. No patient died of rituximab toxicity and all patients who progressed underwent further treatment with chemotherapy. Twenty-three patients received chemotherapy. ORR was 74%, median TTF was 10.5 months and estimated OS was 42 months. Prognostic factors for response included stage, LDH and allograft involvement by tumor. These factors and lack of complete response (CR) predicted poor survival. Twenty-six percent of the patients receiving chemotherapy died of toxicity. Rituximab and chemotherapy are effective in patients with PTLD who fail or do not tolerate RI. While rituximab is well tolerated, toxicity of chemotherapy is marked. PTLD patients requiring therapy beyond RI should be considered for rituximab, especially with EBV-positive disease. Chemotherapy should be reserved for patients who fail rituximab, have EBV-negative tumors or need a rapid response. [source] | ||||||||||||||||||||||||||||||||||||||||