Low-dose Rituximab Research Articles

Successful treatment pure red cell aplasia after ABO major mismatched allogeneic hematopoietic stem cell transplantation with avatrombopag and low dose rituximab.

Pure red cell aplasia (PRCA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with ABO major incompatibility is characterized by transfusion dependent anemia. No standard treatment existed for PRCA following allo-HSCT yet. We conducted a retrospective study, and reported our experience with the use of avatrombopag and lower dose rituximab to treat five patients with PRCA subsequent to major ABO-incompatible allo-HSCT. Five cases of PRCA were identified from 72 patients who underwent allo-HSCT with major or bidirectional ABO mismatch. Cumulative incidence at Day +60 was 6.9% (5/72) at our center. All donor and recipient blood groups were A+ and O+ , respectively. In the first three cases we reported, patients received erythropoietin, plasma exchange, and donor lymphocyte infusion, but none of them had any effect. After 4 weeks of treatment with low dose rituximab (100 mg/week) combined with avatrombopag (40 mg/day), favorable outcomes were obtained. According to the aforementioned experience, Cases 4 and 5 were administered low-dose rituximab and avatrombopag in 3 months after transplantation, and erythroid response was observed on 3 weeks after treatment. Our patients tolerated low-dose rituximab and avatrombopag well and experienced rapid efficacy, with a median duration of 3 weeks. Furthermore, no severe infection or thrombocytosis necessitated a dose adjustment. Low-dose rituximab and avatrombopag may be an effective treatment for patients with PRCA after major ABO-incompatible allo-HSCT. The patients should be treated at least 90 days post transplantation if conventional erythropoietin therapy fails.

The efficacy and safety of low-dose rituximab in the treatment of pemphigus vulgaris: a cohort study

Background Rituximab (RTX) is considered the first-line treatment for pemphigus vulgaris (PV), which is a B-cell-mediated acquired autoimmune disease. However, no consensus on the optimum dosage has been achieved. Objectives To investigate the efficacy and safety of low-dose RTX (a single infusion of 500 mg) for the treatment of PV, a cohort study was conducted for patients with PV, along with a 12-month follow-up following the administration of RTX. Methods Patients with moderate or severe PV were divided into group A (low-dose RTX combined with corticosteroids) and group B (corticosteroids alone). Data on complete remission (CR) rates, doses of corticosteroids, cumulative doses of corticosteroids at the third, sixth, and twelfth months, pemphigus disease area index and adverse effects (AEs) were collected. Results Forty-four patients with moderate or severe PV were enrolled in this study (19 in group A and 25 in group B). Patients treated with low-dose RTX had higher CR rates, lower doses of corticosteroids at the third, sixth, and twelfth months, lower cumulative doses of corticosteroids at the sixth and twelfth months, and fewer AEs than those who received corticosteroids alone. Conclusions This study indicated that low-dose RTX may be a beneficial and secure therapy option for patients with moderate to severe PV.

Case Report: Acquired hemophilia A following COVID-19 vaccine

Background: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and has subsequently been responsible for immense morbidity and mortality. This resulted in the development of vaccines in record time, potentially posing safety issues. Several cases of acquired hemophilia A (AHA) following coronavirus disease 2019 (COVID-19) vaccines have been described in the literature. AHA is a rare autoimmune disease due to the production of IgG autoantibodies to coagulation FVIII that burdens high morbidity and mortality. It is presumed mainly on identifying an increased activated partial thromboplastin time (aPTT), even without bleeding and is confirmed by determining a FVIII inhibitor. To the best of our knowledge, this is the first report of AHA after inactivated virus COVID-19 treated with low dose rituximab (RTX). Lower RTX doses may lead to shorter infusion duration, lower risk of adverse events and lower costs. Case presentation: We report a case of AHA occurring in a 69-year-old man 60 days after an inactivated Sinovac-coronavac COVID-19 vaccine. Diagnosis of AHA was based on clinical presentation and confirmed with prolonged activated partial thromboplastin time, Factor VIII deficiency and the presence of an FVIII inhibitor. Follow-up showed a significant clinical and biological improvement, aPTT was normalized as of 18 days of treatment with corticosteroids along with low dose rituximab. Conclusions: In the literature, the reported cases of AHA following COVID-19 vaccination occurred after Adenoviral Vector DNA- and SARS-CoV-2 mRNA-based COVID-19 vaccines. Here, AHA was presented following inactivated virus COVID-19 vaccine. AHA treated with low dose rituximab can limit occurrence of side effects and the cost of treatment.

Efficacy and safety of low- and ultralow-dose rituximab in neuromyelitis optica spectrum disorder

BackgroundRituximab effectively targets B cells and reduces relapses in neuromyelitis optica spectrum disorder (NMOSD). But the ideal dosage and treatment intervals remain unanswered. We aimed to assess the efficacy and safety of low and ultralow-dose rituximab in NMOSD. MethodsWe conducted a retrospective analysis of NMOSD patients treated with rituximab at two Chinese tertiary hospitals. Patients received either a low-dose regimen (500 mg reinfusion every 6 months) or an ultralow-dose regimen: 100 to 300 mg rituximab based on CD19+B cells (100 mg for 1–1.5% of peripheral blood mononuclear cells, 200 mg for 1.5–5%, and 300 mg for over 5%). ResultsWe analyzed data from 136 patients (41 in the low-dose group, 95 in the ultralow-dose group) with median follow-up durations of 43 and 34.2 months, respectively. Both groups exhibited similar sex distribution, age at disease onset, annual relapse rate, and baseline disease duration. Survival analysis showed that ultralow-dose rituximab was noninferior to low-dose rituximab in preventing relapses. Infusion reactions occurred in 20 of 173 (11.6%) low-dose treatments and 9 of 533 (1.7%) ultralow-dose treatments. B-cell re-emergence was observed in 137 of 236 (58.1%) monitors in the low-dose group and 367 of 1136 (32.3%) monitors in the ultralow-dose group. ConclusionUltralow dose rituximab was noninferior to low-dose rituximab in preventing NMOSD relapses. A randomized controlled trial is essential to validate these findings.

Comparing the Impact of Rituximab Dosing on Longitudinal ADAMTS13 Parameters in TTP

Introduction The use of rituximab to prevent clinical TTP relapse is widely accepted practice. However, the optimal dosing and regimen remains unclear with a variety used across treating centres. ‘Standard’ dosing is extrapolated from dosing for lymphoproliferative diseases: an equally efficacious lower dose would be time & cost-saving. We are investigating the impact of low dose (4 x 200mg weekly) vs standard dose rituximab (4 x 375mg/m 2 weekly) on ADAMTS13 response utilising prospectively collected samples from 69 ADAMTS13 relapse episodes from 4 UK sites who received elective treatment between 2017-2022 (REC: 17/LO/1055). A subset analysis of the cohort was performed, investigating open/closed ADAMTS13 conformation from time of elective rituximab treatment to subsequent rituximab retreatment. Method ADAMTS13 activity was measured at fixed timepoints from first day of elective rituximab on days 1, 8, 15 & 22, month 1, 3, 6 and then 6 monthly until retreatment. Open/closed ADAMTS13 conformation was analysed in a subset of 31 episodes with the 1C4 ELISA and ADAMTS13 antigen ELISA at 4 different timepoints (ADAMTS13 activity <15IU/dL or %; peak ADAMTS13 activity; interim follow-up sample after peak ADAMTS13 and at next ADAMTS13 relapse). Results Median time from one elective rituximab treatment to the next was 16 months (range: 2 - 64, IQR: 9 - 24) for the subset. Time to ADAMTS13 activity normalization was compared in 26 episodes: 5 episodes were excluded as they failed to achieve ADAMTS13 normalization. 17/31 had low dose and 14/31 standard dose. There was no significant difference in the rate of ADAMTS13 normalization in the low dose compared to standard dose rituximab regime, with median 34 days ( IQR: 18 - 99, range: 14 - 266) and 21 days (IQR: 15 - 65, range: 14 - 94) respectively. 13 patients remained in an open ADAMTS13 conformation at all four timepoints, of which 9 had received low dose rituximab. 5 of 13 patients did not achieve a normal ADAMTS13 activity (i.e. >60IU/dL) at any timepoint, with 3 having received low dose & 2 standard dose rituximab. These 13 patients had a slightly shorter time period between elective rituximab treatment episodes with a median of 8 months (range: 2 - 25, IQR: 6 - 15). In 3 patients, ADAMTS13 remained closed on the follow up sample 3 months after peak ADAMTS13 activity (mean 100IU/dL), despite subsequently relapsing 2, 8 & 12 months later. Two had received standard dose rituximab. 14 patients had a closed conformation at peak ADAMTS13 activity, but a subsequent open conformation on follow up sample testing, despite a normal ADAMTS13 activity (median: 82IU/dL, IQR: 72-86). The 7 patients receiving standard dose rituximab converted to an open conformation in 6 months (IQR: 3 - 12) compared to the 7 low dose patients who switched at 4 months (IQR: 3 - 12). Subsequent ADAMTS13 relapse after detection of an open conformation occurred at a median of 6 months later (range: 4 - 8) in the standard dose group and 8 months (range: 4 - 19) in the low dose group. Lastly, 1 patient had no follow up sample after peak ADAMTS13 activity (& closed confirmation), presented with ADAMTS13 relapse (<15IU/dL) and open conformation 7 months later. Of the 31 episodes, ADAMTS13 activity & antigen results were not significantly different between the two rituximab groups for both peak ADAMTS13 activity and follow up timepoints. At peak ADAMTS13 activity, approximately 31% of patients had an open conformation in the standard dose group compared to 69% in the low dose group. In the follow up samples, this increased to 85% open conformation in the standard dose group and 93% open in the low dose group. For two of the patients, with more than one episode of elective rituximab treatment during the study, a closed ADAMTS13 conformation was again achieved after subsequent rituximab treatment. Conclusion We studied the impact of low dose and standard dose rituximab on longitudinal parameters in ADAMTS13 relapse in TTP. Overall, there were no significant differences between open vs. closed conformation at peak ADAMTS13 activity and an interim follow up timepoint between low dose and standard dose rituximab. A higher proportion of patients on low dose rituximab failed to achieve closed conformation at any timepoint but numbers are small. Importantly, our data suggests that regardless of rituximab dose, the open conformation is not indicative of imminent ADAMTS13 relapse as patients required retreatment after a further 7 months on average.

Promising efficacy of Low-Dose rituximab in Muscle specific kinase antibody positive Myasthenia Gravis

AimsThe study aims to evaluate the efficacy of low dose rituximab (RTX) in patients with muscle-specific kinase antibody positive myasthenia gravis (MuSK-MG). MethodsThis is a single-center, retrospective study. A total of 10 patients with MuSK-MG were admitted to the Department of Neurology, First Hospital, Shanxi Medical University, between April 2021 to April 2023. Of them, 9 patients had been treated with low dose RTX (500 mg every 6 month) and recruited in this study. The clinical information, including the severity before and after RTX treatment, were collected from the medical records. Clinical effectiveness was assessed by Myasthenia Gravis Foundation of America (MGFA)-postintervention status (PIS), MG-related activities of daily living (MG-ADL), Quantitative Myasthenia Gravis (QMG) scores, Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r), dosage of steroid at the end of follow up. ResultsAll nine patients showed clinical improvement at the final follow-up after low-dose RTX treatment. The mean dose of prednisolone decreased significantly from 50 mg at baseline to 18.33 mg at the last follow-up (z = -3.417, p = 0.001). The administration of low-dose RTX treatment led to significant improvements in ADL levels (Z = -2.675, P < 0.01), QMG score levels (Z = -2.371, P < 0.05) and QOL-15r levels (Z = -2.547, P < 0.01) at last visit. ConclusionLow-dose RTX is effective for treating MuSK-MG patients. Longer-term follow-up and larger-scale studies are needed to provide further evidence.

Low-dose rituximab in steroid-refractory chronic graft-versus-host disease

BackgroundChronic graft-versus-host disease (cGvHD) is a major complication that puts patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at risk of death or infection. Currently, there is no gold standard for the first-line treatment of patients who do not respond to steroids, and there are several therapeutic options being evaluated in clinical trials for this disease to be used even in the first-line treatment for GvHD. There is evidence of the benefit of rituximab, an anti-CD20 antibody, at a standard dose of 375 mg/m2 weekly in the treatment of steroid-refractory chronic graft-versus disease (SR-cGvHD). ObjectiveTo demonstrate the safety and efficacy of low-dose rituximab in a middle-income center in northeastern Mexico Study designWe report the experience of 26 patients with chronic graft-versus-graft disease who received low-dose rituximab (100 mg weekly for 4 weeks). We utilized the advances in the National Institutes of Health (NIH) criteria for diagnosis, scoring, trial design, and assessment of treatment response. ResultsWe obtained a 5-year overall survival of 23.6%, including four patients with complete response. The 1-year event-free survival was 70% for patients with rituximab. During the treatment, there were 3 hospitalizations, and the causes were: immune thrombocytopenia, a parapneumonic effusion, and a cerebral vascular event. The median length of hospital stay was twelve days. ConclusionA low dose of rituximab is an available and cost-effective option for patients with steroid-refractory cGvHD.

Low Dose Rituximab Efficiently Clears Circulating CLL Cells and Maintains Sensitivity to Antibody Dependent Cellular Phagocytosis (ADCP)

Introduction: We have recently shown that high frequency (2 x week) low dose (50 mg)(HFLD) rituximab (RTX) and acalabrutinib is highly effective initial therapy for patients (n=38) with progressive CLL (ClinicalTrials.gov NCT03788291, PMID:36689726). The first dose of 50 mg of IV rituximab administered at 25 mg/h decreased the median circulating CLL cell count by 84% from pre-treatment baseline at 1h with no further decrease in the count during the remainder of the infusion (PMID:37003030). During the first hour of infusion, median CLL cell membrane CD20 levels decreased to 65% of baseline and were 41% of baseline at the end of the infusion. Median serum rituximab concentration was 2 mcg/ml at 1h and 10 mcg/ml at the end of the infusion. Median complement (CH50) concentration decreased to 91% of baseline at 1 h and to 81% of baseline at the end of the infusion. The cessation of clearance of CLL cells from the circulation within 1h of starting rituximab therapy is thus unlikely to be caused by low rituximab levels, decreased CLL cell CD20 expression or low serum complement levels. We and others have previously shown that ADCP is the primary mechanism of clearance of anti-CD20 mAb opsonized B cells in both humans and mice. We hypothesized that clearance of circulating CLL cells decreases because residual circulating CLL cells are resistant to mAb induced ADCP. To test this hypothesis, we measured in vitro ADCP sensitivity of CLL cells sampled from patients before and after rituximab treatment. Methods: Blood specimens were collected from 13 patients prior to starting therapy (C1D1_pre), 1h after start of IV rituximab infusion (C1D1_1h), at end of rituximab infusion (C1D1_post), and 48 h after initiation of therapy (C1D3_pre). Sensitivity of circulating CLL cells to in vitro ADCP was measured using live cell time-lapse high-content microscopy imaging of phagocytosis of CLL cells by human monocyte derived macrophages (hMDM) as previously described (PMID:32005699). Phagocytosis was quantified using a void index and sensitivity of samples was compared using the area under the curve of the 2h void index plot (AUC). Experiments were done in triplicate with co-cultures of hMDM and CLL cells without mAb as controls. Rituximab (10 mcg/ml) was used to test CD20 mAb mediated ADCP and alemtuzumab (10 mcg/ml) to test non-CD20 mediated ADCP. Results: Figure (median and 95% confidence intervals) shows that neither rituximab nor alemtuzumab induced ex-vivo ADCP as measured by median void index AUC was significantly altered by prior in vivo exposure of CLL cells to rituximab (Wilcoxon Match-Paired Sign test; all p&amp;gt;0.05). Discussion: The rapid decrease in circulating CLL cells induced by IV rituximab occurred only within the first hour after initiation of mAb infusion. Our measurements show that serum rituximab and complement concentrations and CLL cell membrane CD20 levels should be adequate to support additional CLL cell clearance after 1h. We now demonstrate that residual circulating CLL cells remain sensitive to in vitro ADCP by both rituximab and alemtuzumab. This suggests that despite reduced levels of surface antigen, circulating cells remain sensitive to mAb mediated clearance. Alternative explanations for the limited clearance of circulating CLL cells include: 1. Saturation of the limited cytotoxic capacity of the innate immune effector cells (Kupffer cells and splenic macrophages) compatible with our previously reported data on finite macrophage ADCP capacity (PMID:32556153); 2. Mobilization of CLL cells from lymphoid tissue; and 3. Temporary sequestration of rituximab opsonized CLL cells in tissue (e.g. spleen or lungs), which is unlikely given the observed decrease in lymph node size following initiation of therapy. Ongoing research is testing these hypotheses.

Long-Term Efficacy and Safety of Low-Dose Rituximab in Patients with Refractory Myasthenia Gravis

Introduction: Rituximab is a monoclonal chimeric antibody against CD20+ B cells. We aimed to assess the long-term efficacy and safety of CD20+ B cell-guided treatment with low-dose rituximab in refractory myasthenia gravis patients. Methods: Patients with refractory myasthenia gravis treated with rituximab for more than 2 years were included. Rituximab was administered when CD20+ B cells were greater than 1%. We analysed the efficacy of rituximab, treatment interval, side effects, prognosis, and treatment course. Results: A total of 22 patients were included. All patients received 2–12 doses of rituximab, and the median follow-up time was 48.5 months. The scores of the Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Composite were significantly lower than those at baseline (p < 0.05). MGFA-PIS was significantly improved in 21 (95.45%) patients and 14 (63.64%) patients have reached MGFA-PIS minimal manifestations. The average daily dose of prednisone and pyridostigmine bromide and the proportion of immunosuppressants were significantly lower (p < 0.05). Seven patients suffered from 14 worsenings. Eight patients terminated rituximab due to good efficacy. Most patients tolerated rituximab well, although 1 patient had opportunistic infection and hypogammaglobulinemia, 1 patient had an intracranial mass. Conclusion: Long-term CD20+ B-cell-guided low-dose rituximab showed good efficacy and tolerance in patients with refractory myasthenia gravis.

Humoral response to SARS-CoV-2 mRNA vaccine on in ABO blood type incompatible kidney transplant recipients treated with low-dose rituximab

We aimed to evaluate the humoral response after the second and third doses of SARS-CoV-2 mRNA vaccine in ABO blood type incompatible kidney transplant (KT) recipients treated with rituximab. This retrospective study conducted between June 2021 and June 2022 included 131 KT recipients and 154 nontransplant controls who had received mRNA vaccines. We compared the seropositivity (anti-SARS-CoV-2 spike IgG antibody titer ≥ 0.8 U/mL) after the second and third vaccinations. Furthermore, we evaluated the impact of pretransplant vaccination for seropositivity. Of the 131 KT recipients, 50 had received the third dose of mRNA vaccine. The antibody titer was significantly increased after the third dose of mRNA vaccine. The seropositivity rate after the third dose of mRNA vaccine increased from 36 to 70%. We observed no significant difference in seropositivity after the third dose of mRNA vaccine in ABO incompatibility, rituximab use, mycophenolate mofetil use, and age at KT. Of the nine recipients who had received the second or third dose of the mRNA vaccine prior to the KT, eight of the recipients were seropositive both before and after the KT. Our results suggest that ABO incompatibility or rituximab use was not significantly associated with seropositivity.

Efficacy of Low-Dose Rituximab in Primary Immune Thrombocytopenia

Efficacy of Low-Dose Rituximab in Primary Immune Thrombocytopenia

Combination of Rituximab and Low-dose Tacrolimus in the Treatment of Refractory Membranous Nephropathy: A Retrospective Cohort Study

Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory IMN. However, whether RTX single or combined with immunosuppressive therapy is more effective and whether adverse events will increase are still inconclusive. To investigate the efficacy and safety of RTX combined with low-dose tacrolimus (TAC) versus RTX alone in the treatment of refractory IMN. A retrospective cohort study. We retrospectively studied 91 cases of refractory IMN diagnosed between January 2018 and June 2021, all of which immunosuppressive regimens had failed. Thirty-four patients received RTX combined with TAC (RTX + TAC group), and 57 patients were treated with RTX alone (RTX group). The RTX + TAC group was given RTX 1 g once every 2 weeks, two times, and TAC 0.03 mg/kg/day orally. In the RTX group, RTX was given at the same dosage as the RTX + TAC group. Clinical data were collected at 12 months of follow-up to compare the complete and partial remission rates and the incidence of adverse reactions between the two groups. The overall effectiveness rate of RTX + TAC in the treatment of refractory IMN was 87.14%, of which the partial and complete remission rates were 50.01% and 37.13%, respectively, and the median time to complete remission was 9 (interquartile range [IQR] 6.0, 12.0) months. The overall effectiveness rate of RTX was 65.87%, of which the partial and complete remission rates were 39.48% and 26.39%, respectively, and the median time to complete remission was 10.5 (IQR 6.0, 12.0) months. Adverse events occurred in 6 (17.65%) patients in the RTX + TAC group and in 11 (19.30%) in the RTX group (P = 0.473). Proteinuria and high titer of PLA2R are risk factors for non-remission. The complete and partial remission rates of RTX combined with low-dose TAC in the treatment of refractory IMN are higher than those of RTX alone, and no significant increase in adverse events was noted.

#4809 EFFECT OF RITUXIMAB DOSE ON INDUCTION THERAPY IN ABO-INCOMPATIBLE KIDNEY TRANSPLANTATION: A NETWORK META-ANALYSIS USING RECENT DATA

Abstract Background and Aims Rituximab is an essential inducible immunosuppressive agent for ABO-incompatible kidney transplantation (ABOi KT). However, studies on the dosage by country and transplant center are lacking. Therefore, we retrospectively investigated the effects of rituximab induction doses on patient mortality, transplant failure and adverse events. Method We included studies mentioning at least two of the eligible induction doses (200 mg, 200–500 mg, or 500 mg) of rituximab during ABOi KT and associated outcomes such as patient survival, graft failure, and bacterial and viral infections. We performed direct and indirect network meta-analyses using a Bayesian model and ranked different rituximab doses using generational mixed treatment comparisons. Publications from 1970 to February 2020 were searched and analyzed using the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases. GRADE of network meta-analysis approaches specified four levels of certainty for a given outcome: high, moderate, low, and very low. Results Among 5378 patients in 25 trials, glomerular filtration rate, graft loss, antibody-mediated rejection, T-cell-mediated rejection, fungal infection, bacterial infection, and CMV infection did not differ between ABOi groups treated with different doses of rituximab. The effect on mortality was significantly higher in the rituximab 200-500 mg and rituximab 500 mg groups (odds ratio [OR] 2.4, 95% CrI: 1.5-7.4 and OR 1.8.0, 95% CrI 1.2-11.2). The incidence of BK virus was significantly lower in the rituximab 200 mg group than in the other groups. Conclusion In ABO-incompatible kidney transplantation, low-dose rituximab is more effective than high-dose rituximab and reduces the risk of serious infection. Due to the small sample size, further randomized controlled trials may be needed to confirm these findings.

#6888 COMPARISON OF COMBINATION OF RITUXIMAB WITH LOW DOSE THYMOGLOBULIN VERSUS LOW DOSE THYMOGLOBULIN ALONE AS INDUCTION AGENT IN RENAL TRANSPLANTATION

Abstract Background and Aims Current immunosuppressive therapies and protocols have led to significant improvements in early patient and graft survival rates following kidney transplantation. However full dose rATG induction therapy (7-10 mg/kg) has been associated with increased morbidity. There is not much data available on the use of single dose low dose rATG and rituximab, a Anti CD 20 chimeric antibody in low sensitized Indian transplant recipients. To compare the efficacy of low dose single dose rATG(1–1.2mg/kg) versus combination of rituximab with low dose single dose rATG in ABO compatible low sensitization renal transplant recipients. Method Retrospective analysis of all renal transplant recipients between 2010 and 2022 in our center who received low dose rATG(1-1.2mg/kg) or a combination of single dose rituximab(375mg/m2) and low dose thymoglobulin were studied. Demographic data, donor characterstics, HLA matches, infections,rejections was collected Graft function at 3,6 and 12 months post transplant if available was collected. Data was analysed using SPSS 16. Results Of 86 patients studied, 58(67.4%) received single dose of low dose rATG(1-1.2 mg/kg/day) (Grp1) and 28 received a combination of single low dose rATG &amp; Rituximab(375mg/m2)(Grp 2)(32.5%). There was no significant difference between the Grp 1 and Grp 2 in terms of age,gender,vintage of dialysis, PRA status prior to transplant, no of HLA Matches, donor age and Donor GFR. There were 9(15%) of Acute cellular rejections (ACR) in Group1 when compared to 8 (28%) in-group 2(p = 0.263). The number of steroid resistant ACR were 2 (3%)in Grp 1 when compared to 3 (10%)in grp 2(p = 0.365) The number of ABMR were 5(8.6%) in group 1 when compared to 1(3.5%)in grp 2(p = 0.658) 15.5% had graft loss by 1 year in group 1 compared to none in grp 2(p = 0.322)CMV and BKV infections were seen in 1 and no pts and 1 patient in each group respectively.Overall infection rate was 24% when compared to 46.4% in grp 2(p = 0.03). The mean egfr(ml/min/1.73m2) at the end of 3 months, 6 months and 1 year was &amp;95.6,93,95 respectively in grp 1 when compared to 92, 89.4 &amp; 84.3 in grp 2. Conclusion The % of steroid resistant ACR and the number of infections were higher in the 1 year in the Single low dose rATG+Rituximab induction when compared to low single dose rATG alone. However ABMR was lower in the combination grp. Further prospective RCT s are required to establish the role of Rituximab in ABO Compatible transplants.

#6369 RESULTS OF KIDNEY TRANSPLANTATION IN PATIENTS WITH LOW MFI PREFORMED DONOR SPECIFIC ANTIBODIES

Abstract Background and Aims Preformed DSA at transplantation, significantly increase risk of antibody-mediated rejection (ABMR). While pre-existing positive DSA with concomitant positive cross-match is a general contra-indication to kidney transplantation, DSA presence with negative crossmatch is still a controversial topic. The presence of DSA with Mean Fluorescence Index (MFI) up to 3.000 and a negative cross-match is not valued as a contraindication to transplantation and is widely accepted. In some transplant centers the chance of transplantation is also offered to DSA positive patients, with MFI up to 5.000. Aim of this study was to analyze graft and patient survival, acute cellular rejection, humoral rejection, renal function and side effects in kidney transplant recipients (KTR) with positive DSA (MFI up to 3.000) and negative cross-match. Method Nineteen pts (age 53+/-11) with chronic renal failure on chronic hemodialysis treatment (8+/-6 years) received a kidney transplant between May 2017 and December 2020. Median PRA was 66%; 100% pts had DSA with average MFI 2122 (min 1039, max 3779). As immunosuppressive therapies all pts received induction with Thymoglobuline plus Rituximab, followed by maintenance immunosuppression with Tacrolimus, MofetilMycoFenolate and Steroids. All patients were on periodic follow up in our Transplant Clinic. Mean follow up was 26.5+/-14.4 months. Results were compared to a concomitant KTR group DSA and crossmatch negative. Results After 2y follow-up, 17/19 pts are alive (89.5%), one patient died (1/19, 5.2%) after treatment for ABMR. Three patients returned to dialysis treatment (15.8%) during the first year post-tx, because of: PNF 1pt; irreversible ABMR rejection 2 pts. One other patient had reversible ABMR. Cumulative one year graft survival was 79% and the cumulative incidence of ABMR was 15.8%. Average 2 years follow-up creatinine was 1.46+/-0.88 mg/dl, median 2 year GFR was 51+/-25 ml/min. Comparing the matched control group (19 pts DSA and cross-match negative) 2 years patient survival, graft survival, GFR, acute rejection were not significantly different. Incidence of acute rejection was higher in the DSA positive group (16% vs 0%), as well as graft loss (21% vs 12%). Conclusion Our data suggest that low dose Thymoglobuline plus Rituximab induction allow kidney transplantation in recipient with high PRA (69%) and positive DSA with low MFI (&amp;lt; 3.000), with higher risk of acute rejection, and graft loss.

Combining Low-Dose Rituximab and Bortezomib as Immunosuppressive Therapy for Acquired Hemophilia A: 6 Case Series.

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII. Persistently positive inhibitor titers increase the risk of bleeding. Upfront combined regimen with multiple mechanisms has the potential to shorten remission time to lower bleeding risk and reduce immunosuppressor exposure time. We administered lowered dose of rituximab and bortezomib in combination with corticosteroids and cyclophosphamide (rituximab: 100mg weekly × 4 or 500mg once in week 1, bortezomib: 0.65mg/m2 once in week 1, prednisone: 1mg/kg daily, cyclophosphamide: 11.5-2mg/kg daily). We retrospectively analyzed 6 cases (male = 3, female = 3, median age = 51years) treated on this therapeutic regimen. All patients achieved complete remission (range from19 to 66days); adverse event: infection (1/6). This is the first time that this regimen has been reported for treating AHA. It has shown good therapeutic efficacy and the potential to shorten the time to CR. The incidence of adverse events is within a reasonable range. This regimen is feasible and offers a new alternative treatment for AHA.

Efficacy of low-dose rituximab in minimal change disease and prevention of relapse

BackgroundMinimal change disease (MCD) is a major cause of nephrotic syndrome (NS) in children and a minority of adults. The higher tendency to relapse put patients at risk for prolonged exposure to steroids and other immunosuppressive agents. B cell depletion with rituximab (RTX) may be beneficial to the treatment and prevention of frequently relapsing MCD. Therefore, this study aimed to verify the therapeutic/preventive effects of low-dose RTX on the relapse in adult with MCD.MethodsA total of 33 adult patients were selected for the study, including 22 patients with relapsing MCD in relapse treatment group who were treated with low-dose RTX (200 mg per week × 4 following by 200 mg every 6 months) and 11 patients in relapse prevention group with complete remission (CR) after steroid therapy were treated with RTX (200 mg ×1 every 6 months) for preventing the relapse of MCD.ResultsOf the 22 patients with MCD in relapse treatment group, there were 21 cases (95.45%) of remission [2 (9.09%) partial remission (PR), 19 (86.36%) CR], 1 (4.56%) no remission (NR) and 20 (90.90%) relapse-free. The Median duration of sustained remission was 16.3 months (3, 23.5 months, inter quartile range (IQR)). 11 patients in the relapse prevention group during a follow-up of 12 months (9–31 months) had no relapse. The average dose of prednisone in two groups after RTX treatment was significantly lower than before treatment.ConclusionThe results of this study suggested low-dose RTX can significantly reduce relapse rate and steroid dose in adults with MCD with fewer side effects. Low-dose RTX regimens may be beneficial for the treatment of relapsing MCD in adults and may be the preferred regimen for patients at high risk for the development of adverse events from corticosteroids.

Case series of low dose rituximab for membranous nephropathy; a single centre experience

Introduction: Rituximab is the recent treatment of choice for primary membranous nephropathy However, dose of rituximab mentioned in literature is high and not economical in middle income countries. Low dose rituximab based on CD 19 cell count can be tried as an alternative for high dose rituximab for inducing clinical remission in appropriate clinical settings. Case Series: Four patients were administered low dose rituximab and initial CD 19 count was monitored for optimal rituximab response. Three males and one female are part of this case series. Renal biopsies showed membranous nephropathy with tissue phospholipase A2 receptor (PLA2R) positivity in two cases. Serum PLA2R was positive for the same two cases. Two patients completely remitted after one year, one male patient required additional rituximab dose based on CD19 count, one patient required single dose of rituximab for partial remission in the background of tacrolimus with steroids. One patient failed to remit on low dose rituximab protocol. Conclusion: Low dose Rituximab can be tried as a favorable alternative for high dose Rituximab in appropriate clinical settings.

MP31-17 LOW-DOSE RITUXIMAB INDUCTION THERAPY IN IMMUNOLOGIC HIGH-RISK RENAL TRANSPLANTATION PROVIDES FAVORABLE GRAFT OUTCOMES WITHOUT INCREASING CYTOMEGALOVIRUS INFECTION: A 5-YEAR FOLLOW-UP

You have accessJournal of UrologyCME1 Apr 2023MP31-17 LOW-DOSE RITUXIMAB INDUCTION THERAPY IN IMMUNOLOGIC HIGH-RISK RENAL TRANSPLANTATION PROVIDES FAVORABLE GRAFT OUTCOMES WITHOUT INCREASING CYTOMEGALOVIRUS INFECTION: A 5-YEAR FOLLOW-UP Kasumi Yoshinaga, Yuki Maruyama, Tomoaki Yamanoi, Shingo Nishimura, Yusuke Tominaga, Satoshi Katayama, Takehiro Iwata, Kohei Edamura, Tomoko Kobayashi, Yasuyuki Kobayashi, Toyohiko Watanabe, and Motoo Araki Kasumi YoshinagaKasumi Yoshinaga More articles by this author , Yuki MaruyamaYuki Maruyama More articles by this author , Tomoaki YamanoiTomoaki Yamanoi More articles by this author , Shingo NishimuraShingo Nishimura More articles by this author , Yusuke TominagaYusuke Tominaga More articles by this author , Satoshi KatayamaSatoshi Katayama More articles by this author , Takehiro IwataTakehiro Iwata More articles by this author , Kohei EdamuraKohei Edamura More articles by this author , Tomoko KobayashiTomoko Kobayashi More articles by this author , Yasuyuki KobayashiYasuyuki Kobayashi More articles by this author , Toyohiko WatanabeToyohiko Watanabe More articles by this author , and Motoo ArakiMotoo Araki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003264.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We previously reported that low-dose rituximab induction therapy in immunologic high-risk patients for living donor renal transplantation did not increase CMV infections when preemptive therapy was performed. We now report additional long-term outcomes. METHODS: One-hundred thirty-one recipients undergoing living-donor renal transplantation in our institution from May 2009 to September 2021 were evaluated retrospectively. Indications for preoperative rituximab (200 mg/body) were the following: 1. ABO major mismatch, 2. ABO minor mismatch, 3. donor-specific anti-human leukocyte antigen antibody (DSA)-positive, 4. Focal segmental glomerulosclerosis (FSGS). RESULTS: There were 83 patients in the rituximab group and 34 in the non-rituximab group. Groups differed significantly in age (median age, 51 vs 42 years, respectively; P=0.03), but not in sex (male, 66% vs 68% P=1.00), FSGS (4% vs 0%, P=0.56). Estimated glomerular filtration rate did not differ significantly between groups until 5 years after transplantation (Figure 1). CMV clinical symptoms (14% vs 26%, P=0.18), including fever over 38 degrees (8% vs 12%, P=0.73) and gastrointestinal symptoms (7% vs 12%, P=0.06), and the 5-year survival rates of death-censored graft loss (95% vs 96%, P=0.52) did not differ significantly between two groups (Figure 2). CONCLUSIONS: As in our previous study, low-dose rituximab induction therapy was effective in immunologically high-risk recipients without increasing CMV infection without valganciclovir prophylaxis. Furthermore, the graft survival rate and renal function at 5 years after transplantation were equivalent to those in the non-rituximab group. Source of Funding: No © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e436 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kasumi Yoshinaga More articles by this author Yuki Maruyama More articles by this author Tomoaki Yamanoi More articles by this author Shingo Nishimura More articles by this author Yusuke Tominaga More articles by this author Satoshi Katayama More articles by this author Takehiro Iwata More articles by this author Kohei Edamura More articles by this author Tomoko Kobayashi More articles by this author Yasuyuki Kobayashi More articles by this author Toyohiko Watanabe More articles by this author Motoo Araki More articles by this author Expand All Advertisement PDF downloadLoading ...

Can Kunxian Capsule, a Novel Tripterygium Preparation be Used as an Adjuvant Treatment of Early Recurrent Focal Segmental Glomerular Sclerosis After Renal Transplantation? A Case Report

Focal segmental glomerular sclerosis (FSGS) tends to recur after kidney transplantation, particularly when genetic testing is negative. Once the recurrence happens, the renal graft function can rapidly become impaired, following a massive urine protein loss. Despite intensive plasmapheresis and high-dose rituximab treatment, the complete remission rate remains below 50%. The Kunxian capsule, representing a new generation of tripterygium preparation, has shown promising results in controlling proteinuria in patients with IgA nephropathy. It is unclear whether Kunxian capsule treatment would also produce a favorable response in cases of FSGS recurrence. Here we report favorable results with this approach in a patient with early recurrent FSGS after kidney transplantation; we treated this patient successfully with a Kunxian capsule, a low dose of rituximab (200 mg), and reduced sessions of plasmapheresis. Complete remission, with a 90% reduction in total urine protein (0.81 g/24 h vs 8.3 g/24 h), was achieved within 2 weeks post-treatment. Of interest, the complete remission state in this patient has been maintained over 20 months with continuous administration of Kunxian capsules after the cessation of plasmapheresis. The potential mechanisms involved here include direct podocyte protection and the anti-inflammatory and immunosuppressive properties of triptolide in the Kunxian capsule. Our case may offer a new reference option for treating recurrent FSGS in the future.