Single Dose Of Rituximab Research Articles

Successful preemptive therapy with single-dose rituximab for Epstein-Barr virus infection to prevent post-transplant lymphoproliferative disease after pediatric hematopoietic stem cell transplantation.

The efficacy of preemptive treatment containing rituximab to prevent post-transplant lymphoproliferative disease (PTLD) in children has not yet been fully elucidated. We analyzed 19 pediatric patients who developed high Epstein-Barr virus (EBV) DNAemia (EBV viral load of greater than 40000copies/mL) after allogeneic hematopoietic stem cell transplantation (HSCT) and were preemptively administered rituximab. Rituximab was intravenously injected at a dose of 375mg/m2 once the EBV viral load was greater than 40000copies/mL. In all 19 patients, EBV DNAemia was eradicated after a median of 9days (range, 3-20days), and PTLD did not occur. One patient had transient fever, and four patients did not fully recover B cell counts after transplantation. We suggested that delayed B cell recovery was caused by chronic graft-versus-host disease (GVHD) related drugs, not rituximab administration. And there were no other infection-related side effects. In conclusion, preemptive therapy containing rituximab is expected to reduce the incidence of PTLD after HSCT and improve post-transplantation outcomes in children.

Favorable Response in Statin-Naive Paraneoplastic Anti-HMGCR Antibody–Associated Myopathy to Single Dose of Rituximab and Persistent Remission With Management of Underlying Lung Cancer

Anti-HMGCR myopathy is a subtype of immune-mediated necrotizing myopathy, typically associated with exposure to statins, although a sizable minority in some cohorts are statin-naive. Although the clinical features of acute- or subacute-onset symmetrical proximal muscle weakness mimic those of other idiopathic inflammatory myopathies, necrotizing myopathy is distinguished by the histopathological findings of muscle fiber necrosis and regeneration with little to no accompanying inflammation. Several recent studies of patients with anti-HMGCR myopathy have identified a slightly increased risk of cancer. Most patients require aggressive immunotherapy, usually as a combination of 2 or 3 immunosuppressant drugs. We report a case of a statin-naive paraneoplastic anti-HMGCR myopathy, who unlike other reported cases, responded to a single dose of 1000 mg of intravenous rituximab and subsequent chemoradiation therapy for an underlying lung cancer, despite failing to completely respond to prior high-dose oral prednisone and methotrexate.

Comparative Efficacy of Bortezomib and Carfilzomib Desensitization Protocols in Highly Sensitized Cardiac Transplant Candidates

Purpose At our center, patients who are deemed highly sensitized may undergo a proteasome inhibitor-based desensitization protocol to shorten organ wait time and improve the probability of finding an acceptable donor. The purpose of this study is to evaluate the comparative effects on detectable anti-HLA antibodies between our center's bortezomib-based and carfilzomib-based protocol in sensitized patients awaiting heart transplantation. Methods This was a retrospective cohort study. Highly sensitized patients awaiting cardiac transplant who underwent the desensitization protocol between April 2013 and February 2017 were included in the study. Protocol included either a bortezomib or carfilzomib-based regimen with multiple plasmapheresis sessions and a single dose of rituximab. Efficacy of these two desensitization regimens was evaluated by comparing trends in pre- and post-protocol positive (mean fluorescence intensity (MFI) greater than 500) anti-HLA antibody allele specificities. Results Of the 19 patients who underwent a desensitization protocol, 8 patients received a bortezomib-based regimen and 11 patients a carfilzomib-based regimen. When comparing trends in both HLA class I and class II antibodies pre- and post- desensitization protocol, patients who received a bortezomib-based regimen experienced a greater reduction (p Conclusion In our observed cohort, bortezomib-based desensitization protocol was associated with a greater percent reduction of anti-HLA antibody alleles with MFI>500 compared to the carfilzomib-based desensitization protocol. Larger, prospective randomized studies are needed to confirm these results.

Cardiac Transplantation across Preformed HLA-Antibody Barriers: Results of a Peritransplant Desensitization Protocol

Purpose A growing number of patients awaiting heart transplantation presents with preformed anti-HLA antibodies. This allosensitization prolongs waiting times and increases morbidity and mortality. In 2017, we designed aprotocol for peritransplant desensitization of heart-transplanted patients showing preformed anti-HLA donor specific antibodies (pfDSA), i.e. a positive virtual crossmatch. The protocol included: an intraoperative single dose of the IL-6 receptor antibody Tocilizumab (10mg/kg) just before releasing the aortic clamp; 5 sessions of plasmapheresis (PE, 1 before transplantation, 1 during transplantation and 3 thereafter); an infusion (2g/kg) of IgA and IgM-enriched human immunoglobulins G (IgGAM) after the last PE; and a single Rituximab dose (375mg/m2) after IgGAM. IgGAM are repeated every 4 weeks (0.5g/kg) for a maximum of 6 months, if DSA are still positive. Aim of this study was to present the preliminary results of this peritransplant desensitization protocol. Methods Records of heart-transplanted patients at our institution between 01/2017 and 10/2018 were reviewed. Patients with pfDSA (positive virtual crossmatch) formed the case group, remaining patients the control group. Median (IQR) follow-up amounted to 9 (5, 16) months. Results During the study period, among the 42 transplanted patients, 9 (21%) patients formed the case group and the remaining 33 (79%) the control group. All 9 case patients showed pfDSA with >50% pre-transplant panel reactive antibodies (PRA). Pretransplant recipient and donor characteristics did not differ between groups. Post-transplant, no case patients showed severe primary graft dysfunction, but 6 (19%) control patients did (p=0.19). At treatment end, pfDSA were cleared in 4 (44%) patients. At 1-year follow-up, survival was 100% vs. 75% in case and control patients (p=0.18); freedom from biopsy-confirmed rejection (Grade >1R) was 89% vs. 92% in case (n=1) and control (n=2) patients (p=0.78); and from steroid-pulsed therapy 89% vs. 82% in case (n=1) and control (n=5) patients (p=0.76), respectively. One case patient showed minimal AMR (pAMR 1+). Conclusion The present study showed that heart transplantation across positive crossmatch barriers can be feasible and safe. The present peritransplant desensitization protocol yielded good survival and rejection-free survival.

Are only pre-transplant rituximab and plasma exchange sufficient for desensitization protocol of ABO incompatible LDLT?

Introduction: ABO incompatible living donor liver transplantation (ABOi LDLT) has become a feasible option because of improved outcomes by various desensitization strategies. However, the protocol of ABOi LDLT has not been established worldwide. Nevertheless, the results after transplantation are homogenous. The reports for the results of ABOi LDLT using only rituximab and plasma exchange are scarce. We present the outcomes of our desensitization protocol for ABOi LDLT. Method: From January 2015 to August 2018, we performed 117 LDLTs. Of them, 29 patients (25%) received ABOi LDLT. We used only a single dose of rituximab(300 mg/m2) and several plasma exchanges for pre-transplant desensitization in ABOi LDLT and post-transplant immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil and steroid. The target iso-agglutinin IgG titer before transplantation and during post-transplant period were 1:32 and 1:64. Result: The mean initial iso-agglutinin IgG titer was 131 (range, 4∼512) and initial iso-agglutinin IgG titer in recipient blood type O was higher than in another blood types. Pre-transplant plasma exchanges were performed in all recipients with more than target titer (mean number of sessions, 2.32 (range, 1∼5)). Post-transplant plasma exchanges were performed in 3 patients because of higher target isoaaglutinin titer (> 1:64), but none had antibody mediated rejection. Biliary complications were identified in 8 patients, but all was anastomotic site stricture. Acute cellular rejection was confirmed in one patient and resolved by steroid pulse therapy. Conclusion: Both rituximab and plasma exchange along are one of desensitization strategies to eliminate the risk of antibody mediated rejection and our results were also comparable to ABO-identical or compatible LDLT. Hence, we believe that complex protocols including splenectomy, intravenous immunoglobulin, and local infusion therapy are not necessary in most ABOi LDLT.

Adjuvant rituximab, a potential treatment for the young patient with Graves’ hyperthyroidism (RiGD): study protocol for a single-arm, single-stage, phase II trial

IntroductionGraves’ disease (Graves’ hyperthyroidism) is a challenging condition for the young person and their family. The excess thyroid hormone generated by autoimmune stimulation of the thyroid stimulating hormone receptor on...

ABO-incompatible liver transplantation using only rituximab for patients with low anti-ABO antibody titer.

Backgrounds/AimsGraft survival after ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has increased due to advances in desensitization methods. We analyzed early outcomes following ABOi LDLT using only rituximab without any additional desensitization methods in recipients with low anti-ABO antibody titers (≤1:32).MethodsTen adult patients underwent ABOi LDLT between September 2014 and December 2016. All patients were administered a single dose of rituximab (300 mg/m2) prior to LDLT. Three patients with baseline anti-ABO titer >1:32 underwent multiple sessions of plasmapheresis to reduce titers to <1:32 (rituximab+plasmapheresis, RP). Seven patients with low anti-ABO titer (≤1:32) did not undergo plasmapheresis (rituximab-only, RO). ABO-compatible LDLT patients during the same period were included for comparison (n=22).ResultsPost-transplantation titers were significantly lower in the RO than in the RP and showed no rebound rise (POD7 1.14±0.38 vs 28.0±31.7, p=0.04), (POD30 1.26±0.45 vs 108±107, p=0.02). There were no significant differences in rejection, biliary complications and infection between groups. There were no significant differences in outcome between the RO group and ABO-compatible except for infection.ConclusionsThis study shows that recipients with low baseline anti-ABO antibody titer (≤1:32) can undergo ABOi LDLT using conventional immunosuppression and rituximab alone.

FEW PULMONARY MASSES CAN BE LIFE THREATENING: RAPIDLY PROGRESSING CASE OF GRANULOMATOSIS WITH POLYANGITIS

SESSION TITLE: Diffuse Lung Disease 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 pm - 02:15 pm INTRODUCTION: Granulomatosis with polyangiitis (GPA), formerly called Wegener Granulomatosis, is a necrotizing granulomatus inflammation-involving small to medium sized vessels. Early diagnosis and treatment is a key otherwise mortality and morbidity remains high from multi organ failure. Here we describe a rare case of 48 year old Hispanic male with rapidly progressing GPA who responded remarkably well to immunosuppressive therapy. CASE PRESENTATION: A 48-year-old Hispanic male was admitted for pneumonia and possible stroke symptoms. He had a 20-pound weight loss in addition to headaches, vision problems, and weakness. CT chest revealed multiple pulmonary masses. He was started on broad-spectrum antibiotics and then transferred to our facility for further care. Bronchoscopy showed predominant lymphocytes in bronchoalveolar lavage. Percutaneous biopsy of mass did not show changes of vasculitis. His respiratory status started to decline with hemoptysis. He also developed acute kidney injury that progressed to acute renal failure requiring hemodialysis. Proteinase 3 autoantibody (PR3) levels came back elevated. Based on his clinical presentation, diagnosis of GPA was suspected and he was started on IV steroids and Cyclophosphamide. He also got a single dose of Rituximab. Percutaneous renal biopsy was done which later on showed necrotizing cresentic pauci immune C-ANCA mediated glomerulonephritis. Eventually his renal function recovered and was taken off dialysis. He was discharged on oral steroids and immunosuppressive therapy to be managed by Rheumatology. DISCUSSION: Granulomatosis with polyangiitis (GPA) is usually more common in older adults especially in Caucasian population. Our case involved a Hispanic male. Studies have shown that Hispanic patients with these associated vasculitides have more severe disease and more extensive organ damage. We started immunosuppressive therapy based on clinical findings, anti-PR3 antibody without waiting for renal biopsy to save organs. CONCLUSIONS: While, the presenting symptoms of GPA can be vague and nonspecific, patient can rapidly progress to classical findings. Rapid diagnosis is a key since aggressive therapy is needed to help prevent multi-organ damage and subsequent failure. We recommend starting immunosuppressive therapy early without waiting for confirmatory biopsy if there is a threat to any of the organs and the clinical symptoms are highly suspicious for GPA. Reference #1: Flores-Suárez LF, Villa AR. Spectrum of Wegener granulomatosis in a Mexican population. Ann NY Acad Sci. 2007; 1107: 400-9. DISCLOSURES: No relevant relationships by Alexander Goldstein, source=Web Response No relevant relationships by Muhammad Malik, source=Web Response No relevant relationships by Kim Nguyen, source=Web Response No relevant relationships by Manish Patel, source=Web Response No relevant relationships by Grace Wang, source=Web Response

Cardiac transplantation across preformed HLA-antibody barriers

Cardiac transplantation across preformed HLA-antibody barriers

Therapeutic efficacy of rituximab for the management of adult-onset steroid-dependent nephrotic syndrome: a retrospective study.

Recent reports have described the efficacy of rituximab in treating steroid-dependent nephrotic syndrome (SDNS) in pediatric patients. However, few reports describe data regarding adult-onset SDNS. We investigated the efficacy of rituximab for the management of adult-onset SDNS. We performed a retrospective cohort study investigating eight patients with adult-onset SDNS who were treated with rituximab. Clinical data were obtained at the initiation of rituximab therapy. The primary outcomes evaluated were successful suppression of relapses and CD19+ cells after rituximab treatment. The corticosteroid- and immunosuppressant-sparing effect and adverse events were additionally evaluated. All eight patients were diagnosed with minimal change nephrotic syndrome and received immunosuppressants in addition to corticosteroid. Total number of relapses was 10.5 times as a median value. Rituximab administration was repeated in two patients, whereas six received single-dose rituximab. Three of eight (37.5%) patients showed relapse after rituximab therapy. A rituximab-induced depletion in CD19+ cells noted initially was followed by their reappearance in all patients. There were cases with no relapse after the reappearance of CD19+ cells. The median relapse time pre- and post-rituximab therapy showed a decrease from 1time/year (interquartile range [IQR] 1-3times/year) to 0time/year (IQR 0-1time/year). Rituximab treatment induced a significant reduction in the required doses of corticosteroid and cyclosporine (P < 0.01). No serious adverse events were observed. Rituximab treatment was effective not only in childhood-onset but also in adult-onset SDNS. Further studies are needed to establish optimal treatment regimens.

Post-transplant lymphoproliferative disorder presenting on post-transplant Day 35 as a pulmonary parenchymal infiltrate—a case report

Post-transplant lymphoproliferative disorder (PTLD), a rare but serious complication of solid organ transplantation, is classified into early-onset and late-onset subtypes. Early-onset PTLD occurs a median of 4–11 months after lung transplantation. It rarely presents in the first 2 months post-transplant. Early-onset PTLD usually presents as a solitary pulmonary nodule. We present a unique case of early-onset PTLD that was diagnosed on post-operative Day 35 and presented as a pulmonary parenchymal infiltrate. This case is also exceptional in that the patient had a significant clinical response to only a single dose of rituximab.

Donor Specific Antibody Shows Different IgG Subtype in Early versus Late Antibody Mediated Renal Allograft Rejection

Background Early and late antibody mediated rejection (EAMR/LAMR) are immunologically distinct entities and represent major risk factors for allograft survival in renal transplantation. The aim of this study was to describe the nature of donor-specific anti-HLA antibodies (DSA) that mediate EAMR and LAMR, and to correlate these data with DSA mean fluorescence intensity (MFI) response to proteasome-inhibitor (PI) therapy. Methods DSA levels (Day 0 and Day 50 therapy) were determined in 35 (11 EAMR + 24 LAMR) patients who received PI-based AMR therapy (1 or two bortezomib cycles +/- a single rituximab dose (375mg/m2)). All patients had at least 9 months of follow-up after AMR therapy. EAMR was defined as occurring within 6 months after transplantation. All donors and recipients had HLA-A,-B,-C,-DRB1, DRB3/4/5,-DQB1, DQA1 and DPB1 typing by molecular methods, and all cases were transplanted after negative prospective flow T- and B-cell crossmatches. AMR was diagnosed using Antibody Working Group and Banff criteria. Anti-HLA donor-specific antibody were identified by Luminex single-antigen beads (One Lambda) using both the generic IgG and IgG1-4 subtype-specific mAb (PE-conjugated, Southern Biotech). Epitope fingerprints were used to assess the therapeutic response (figures). Results 33 DSA were detected in EAMR (11 class I, 22 class II) and 52 DSA in LAMR (11 class I, 41 class II). DSA Class distribution was 43 anti-HLA class I, 27 anti-HLA DR, 50 anti-HLA DQ and 4 anti-HLA DP. Anti-HLA DQ DSAs were found in 3/11 EAMR vs 18/24 LAMR (p=0.01). IgG1 was detected in all patients, IgG2 was detected in 3/11 EAMR and 5/24 LAMR, IgG3 was present in 15/24 LAMR versus 0/11 EAMR (p=0.007), and IgG4 was detected in 2/11 EAMR vs 6/24 LAMR. There were 4/11 EAMR versus 16/24 LAMR patients with multiple IgG subtypes. The DSA MFI reduction at 50 days after PI therapy was 79±22% in EAMR versus 30±26% in LAMR (p=0.00001).. Summary Late AMR demonstrated: 1) a greater number of de novo DSAs; 2) a greater proportion of anti-HLA class II DSA, especially anti-HLA DQ; 3) a higher proportion of IgG3, the subtype with the highest affinity for complement (C1q) binding; 4) a higher degree of multiple IgG subtypes. 5) lesser response in DSA reduction with PI therapy.

Are only Pre-Transplant Rituximab and Plasma Exchange Sufficient for Pre-Transplantation Desensitization Protocol of ABO incompatible LDLT?

Backgrounds ABO incompatible living donor liver transplantation (ABOi LDLT) has become a feasible option because of improved outcomes by various desensitization strategies. However, the protocol of ABOi LDLT has not been established worldwide. Nevertheless, the results after transplantation are homogenous. The reports for the results of ABOi LDLT using only rituximab and plasma exchange are scarce. We present the outcomes of our desensitization protocol for ABOi LDLT. Methods From January 2015 to December 2016, we performed 61 LDLTs. Of them, 14 patients received ABOi LDLT. We used only a single dose of rituximab (375 mg/m2) and several plasma exchanges for pre-transplant desensitization in ABOi LDLT and post-transplant immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil and steroid. The target iso-agglutinin IgG titer for transplantation was 1:32. Results The mean initial ranges of iso-agglutinin IgG titers were 124 (range, 4~256). We performed pre-transplant plasma exchange in all recipients (mean number of sessions, 3 (range, 2~5)). The mean peak iso-agglutinin IgG titer after transplantation was 19.5 (range, 0~64). Post-transplant plasma exchange for antibody mediated rejection and rebound elevation of iso-agglutinin titer was not required. One patients received splenectomy with transplantation to prevent small for size graft syndrome. Biliary complications were identified in 5 patients and resolved by biliary stent via percutaneous or endoscopic approach. But, diffuse intra-hepatic biliary stricture was not found in all recipients during short-term follow-up period. The other complications were not identified. Conclusions Both rituximab and plasma exchange along are one of desensitization strategies to eliminate the risk of antibody mediated rejection. And, we believe that complex protocols with splenectomy, intravenous immunoglobulin, and local infusion therapy are not necessary in most ABOi LDLT.

ABO-Incompatible Liver Transplantation Using only Rituximab for Patients with Low Anti-ABO Antibody Titer

Background Graft survival after ABO-incompatible living donor liver transplantation (LDLT) has increased due to advances in desensitization methods. We analyzed early outcomes following ABO-incompatible LDLT without plasmapheresis in recipients with low anti-ABO antibody titers (1:32). Methods Ten adult patients underwent ABO-incompatible LDLT between September 2014 and December 2016. All patients were administered a single dose of rituximab (300 mg/m2) prior to LDLT. Three patients with baseline anti-ABO titer >1:32 also underwent multiple sessions of plasmapheresis to reduce titers to 1:32 or lower (rituximab + plasmapheresis, RP). Seven patients with low anti-ABO titer (1:32) did not undergo plasmapheresis (rituximab-only, RO). Adult ABO-compatible LDLT patients during the same period were included for comparison (n=22). Results Post-transplantation titers were significantly lower in the RO than in the RP and showed no rebound rise (POD7 1.14±0.38 vs 28.0±31.7, p=0.04), (POD30 1.26±0.45 vs 108±107, p=0.02). There were no significant differences in rejection, biliary complications, or infection between the RO and RP group. There were no significant differences in outcome between the RO group and ABO-compatible except for rate of infection (RO: 57.1%; ABO-compatible: 9.1%; p=0.02). Conclusions This study shows that recipients with low baseline anti-ABO antibody titer (≤1:32) can undergo ABO-incompatible LDLT using conventional immunosuppression and rituximab alone.

Impact of Positive Donor-Specific HLA Antibodies Crossmatch on Graft Survival in ABO-Incompatible Liver-Kidney Transplantation: A Case Report

We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.

A comparison of desensitization methods: Rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation

BackgroundPlasmapheresis is a desensitization method used prior to ABO-incompatible (ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking. MethodsFifty-six adult patients underwent ABO-I living donor liver transplantation between January 2012 and October 2015. A single dose of rituximab (300 mg/m2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014 (RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015 (RO group, n = 30). ResultsThe 6-, 12- and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively (P = 0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications. ConclusionsSufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.

Capillary leak syndrome as a complication of antibody-mediated rejection treatment: a case report.

We report a case of capillary leak that developed during treatment of antibody-mediated rejection in a kidney transplant recipient. A 53-year-old female transplant recipient experienced an increase in serum creatinine from 1.1 to 1.8mg/dL. Antibody-mediated rejection was diagnosed by graft biopsy. She was treated with five plasmapheresis sessions (on alternate days with albumin replacement), five doses of immunoglobulin (5g/dose at 100mg/kg), a single dose of rituximab (500mg), and four doses of bortezomib on days 1, 4, 7, and 10 (1.72mg/dose at 1.3mg/m2 body surface area). During treatment, edema, slight diarrhea, pancytopenia, hypoalbuminemia, peripheral neuropathy, and postural hypotension were noted. Despite control of liquids, she presented with edema progressing to an increase of more than 10kg body weight. Prerenal acute graft dysfunction associated with hypotension was diagnosed on day 12, heart failure or other infectious complications being discounted. On day 13, daily hemodialysis was prescribed, and a stable volume status was reached after five hemodialysis sessions. On day 20, the patient recovered diuresis and the edema and diarrhea abated, but she remained on chronic hemodialysis. After excluding other causes of distributive shock, the diagnosis of capillary leak syndrome was based on the presence of hypotension, generalized edema, and hypoalbuminemia in the absence of significant proteinuria. The concomitant presence of diarrhea, peripheral neuropathy, and pancytopenia, suggest a possible causal role for bortezomib. Awareness by clinicians of capillary leak syndrome associated with bortezomib-based treatment of AMR is paramount, despite its rarity.

Incidence of Hepatitis B Viral Reactivation After Kidney Transplantation With Low-Dose Rituximab Administration.

In hematological malignancy patients intended to receive rituximab, hepatitis B virus (HBV) serology screening, viral reactivation monitoring, are recommended. However, the effect of single-dose rituximab (RIT) on HBV reactivation in kidney transplant patients with previous HBV infection is still unclear. In this retrospective cohort study consisting of 1294 kidney transplant patients, we identified 76 patients showing preoperative hepatitis B surface antigen-negative, hepatitis B core antibody-positive, and HBV-DNA-negative results. A rituximab dose of 200 mg/body was administered to 48 patients, 46 of whom did not receive prophylaxis (RIT+ group). Twenty-eight patients received neither rituximab nor prophylaxis (RIT- group). We monitored HBV-DNA by polymerase chain reaction every 1 to 3 months, and HBV reactivation was defined as detectable HBV-DNA. HBV reactivation was found in 1 patient in the RIT+ group (2.2%) and 1 patient in the RIT- group (3.6%) at 6 weeks and 5.5 years posttransplant, respectively, but spontaneously cleared. Both patients showed positive hepatitis B surface antibody preoperatively. HBV reactivation was not found in 6 patients lacking anti-hepatitis B surface preoperatively. Low-dose RIT administration in kidney transplant patients without prophylaxis is associated with low incidence of HBV reactivation. However, the comparisons among standard-dose RIT, low-dose RIT, and controls with high-quality study design is necessary.

Rituximab as a Therapeutic Option for Steroid-Sensitive Minimal Change Nephrotic Syndrome in Adults.

Minimal change nephrotic syndrome (MCNS) usually responds to steroids but frequently relapses, requiring additional treatment with immunosuppressive agents. Rituximab is a chimeric murine/human monoclonal immunoglobulin G1 antibody that targets CD20, a B-cell differentiation marker. B-cell recovery begins at approximately 6 months following the completion of treatment. Rituximab has a beneficial effect, with the sustained remission or reduction of proteinuria in patients with steroid-dependent MCNS. Relapses are thought to be associated with an increase in CD19 cells. The mean serum half-life of rituximab was reported to be 10-15 days in patients with steroid-dependent MCNS. Only infusion reactions, such as rash and chills, occurred after single-dose rituximab infusion and can be managed by pre-medication or infusion rate adjustments. Even though severe adverse effects of rituximab are not expected, we must be aware of potentially life-threatening adverse effects. Controlled randomized trials that include adult patients with steroid-dependent MCNS are required to prove the efficacy and safety of rituximab and to evaluate the cost-effectiveness of rituximab treatment. In this review, we highlight recent studies and discuss the effects of these studies on the management of patients with MCNS in adults.

Low-dose Rituximab therapy in resistant idiopathic membranous nephropathy: single-center experience.

ABSTRACTBackgroundPersistent significant proteinuria has been associated with increased risk of progression to end-stage kidney disease in patients with idiopathic membranous nephropathy (IMN). Rituximab (RTX) therapy has given encouraging results in IMN, but most of the studies have used a higher dose, which is limited by the high cost as well as a potential increased risk of infections. Our study aimed to assess the efficacy and safety of low-dose RTX in patients with immunosuppression-resistant IMN.MethodsA total of 21 patients with treatment-resistant IMN treated with RTX from 2015 to 2016 at our center were included in the study. They received two doses of RTX (500 mg each) infusion 7 days apart. CD19 count was performed after 4 weeks. A single dose of RTX was repeated after 4–6 weeks if CD19 count was not depleted.ResultsThe mean standard deviation age of patients was 33.3 ± 12.3 years and 33.3% were females. Mean proteinuria before RTX therapy was 6.2 ± 2.2 g/day, serum creatinine was 0.9 ± 0.3 mg/dL and estimated glomerular filtration rate (eGFR) was 95.8 ± 26.9 mL/min/1.73 m2. All the patients were non-responders to prior immunosuppressive treatment. Twenty (95.2%) patients achieved targeted CD19 depletion with two doses of RTX. One patient required one additional RTX dose due to inadequate B-cell suppression. A total of 13 (61.9%) patients achieved remission with RTX therapy: 4 (19.0%) complete and 9 (42.9%) partial remission. Patients who did not respond to RTX had a significantly lower baseline eGFR compared with those who achieved remission (P = 0.022). One patient developed respiratory tract infection following RTX during the follow-up, which responded to a course of oral antibiotics. During median follow-up of 13.1 (10–23.9) months, four (19%) patients had deterioration in renal function and one patient relapsed after achieving partial remission. Renal survival was significantly better in patients who responded to RTX therapy as compared with those who did not achieve remission (P = 0.0037).ConclusionLow-dose RTX therapy is effective and safe in immunosuppression-resistant IMN.