Single Dose Of Rituximab Research Articles

The effect of rituximab on patient reported outcomes in the preclinical phase of rheumatoid arthritis: 2 year data from the PRAIRI study

ObjectivesEarly treatment of individuals at risk of developing rheumatoid arthritis (RA-risk) in the preclinical phase has the potential to positively impact both patients and society by preventing disease onset and...

Relapse during and after regular single-dose rituximab treatment in adult patients with steroid-dependent nephrotic syndrome.

Rituximab is widely used in patients with steroid-dependent nephrotic syndrome. However, information on the effect of long-term rituximab treatment is limited. This study examined the efficacy of rituximab during and after treatment in adult patients with steroid-dependent nephrotic syndrome. This retrospective cohort study included 30 patients with steroid-dependent nephrotic syndrome. Patients received regular single-dose rituximab (500mg) intravenously every 6months. Discontinuation of rituximab was considered after four to six doses if there was no recurrence of nephrotic syndrome. Glucocorticoid discontinuation with remission, first relapse after rituximab initiation, and relapse after regular rituximab treatment discontinuation were evaluated. The median age was 38 (range 18-67) years. Of 30 patients, 13 and 17 were men and women, respectively. Prior to rituximab treatment, the median number of nephrotic syndrome relapses in the patients was 5 (range 2- > 20). The 1year discontinuation rate of glucocorticoids with remission was 83%. All patients discontinued glucocorticoid treatment at least once until 3years and 7months. The 1 and 2year relapse rates after initiation of rituximab treatment were 0% and 3%, respectively. 25 patients discontinued regular rituximab treatment after a median number of six (4-12) doses. Six patients relapsed after discontinuing rituximab, and the 1 and 2year relapse rates after the last regular rituximab treatment were 9% and 25%, respectively. All patients with steroid-dependent nephrotic syndrome who received rituximab could discontinue glucocorticoid treatment with remission, and three-fourths of the patients remained in remission for > 2years after discontinuing rituximab treatment.

Comparison of estimated blood loss during living kidney transplantation according to the number of double-filtration plasmapheresis

BackgroundPlasmapheresis is an important preoperative desensitization treatment for ABO-incompatible living kidney transplantation. However, in cases with plasma exchange therapy (PET), it is necessary to consider the risks of perioperative bleeding and healthcare economic costs. This study investigated the association between intraoperative blood loss and the frequency of preoperative double-filtration plasmapheresis (DFPP) and explored the correlation between DFPP frequency and coagulation factors. Furthermore, the study examined the incidence of perioperative bleeding complications.MethodsWe enrolled 294 patients (205 men and 89 women) who underwent living kidney transplantation at our institution between January 2020 and March 2023, without PET or with only DFPP performed as PET. A single dose of rituximab (200 mg) was administered to ABO-incompatible living kidney transplant patients within 7 days before transplantation. In these patients, PET was performed until anti-blood group IgG and IgM antibody titers were reduced to 32 times or less.ResultsThe intraoperative blood loss increased in accordance with the DFPP sessions. The amount of bleeding significantly increased when DFPP was performed ≥ 2 sessions. Considering this, we initiated serum fibrinogen level measurements from the middle of the study and observed that serum fibrinogen levels decreased in correlation with the number of DFPP sessions. Fibrinogen levels dropped to critical levels (< 100 mg/dL) after three sessions of DFPP. Within the entire cohort, four patients (1.4%) underwent post-transplantation hematoma removal surgery, and among them, three had received DFPP before transplantation.ConclusionsThe number of DFPP procedures was associated with the amount of bleeding and serum fibrinogen levels during living kidney transplantation.

Single-Dose Rituximab Plus Glucocorticoid Versus Cyclophosphamide Plus Glucocorticoid in Patients with Newly Diagnosed Acquired Hemophilia a: A Multicenter, Open-Label, Randomized Clinical Trial

Introduction Cyclophosphamide plus glucocorticoid is a first-line immunosuppressive therapy for acquired hemophilia A (AHA), a serious bleeding disorder, but brings risks of myelosuppression, secondary tumor, and reproductive toxicity. Rituximab plus glucocorticoid therapy shows comparable efficacy but lacks results from randomized controlled trials. We aimed to establish whether the single-dose rituximab regimen was non-inferior to the cyclophosphamide regimen. Methods This study was the first noninferiority, multicenter, open-label, randomized controlled clinical trial comparing these two combination therapies in AHA patients (ClinicalTrails.gov number, NCT03384277). Adult patients (18-80 years) with newly diagnosed AHA from five centers in China were randomly assigned 1:1 to receive glucocorticoid (methylprednisolone 0.8 mg/kg per day for the first 3 weeks and then tapered) plus single-dose rituximab (375 mg/m 2) or plus cyclophosphamide (2 mg/kg per day until inhibitor becomes negative, for a maximum of 5 weeks). The primary outcome was complete remission (CR, defined as FVIII activity ≥ 50 IU/dL, FVIII inhibitor undetectable, immunosuppression tapered and no bleeding for 24 hours without bypassing agents) rate measured within 8 weeks. The noninferiority margin was an absolute difference of 20%. The secondary outcomes included partial remission (PR) rate, time to PR, time to CR, time for inhibitor titer to decrease by 50% of baseline, relapse rate, time to relapse and so on. Safety was assessed in all patients. Results Between December 29, 2017 and June 9, 2022, 67 patients were screened, of whom 63 (33 female and 30 male) were assigned: 31 to single-dose rituximab group and 32 to cyclophosphamide group. The baseline characteristics of these patients were balanced between the single-dose rituximab group and cyclophosphamide group. Twenty-four (77.4%) patients in the rituximab group and twenty-two (68.8%) patients in the cyclophosphamide group achieved CR, which showed the noninferiority of the single-dose rituximab-based regimen (absolute difference=-8.67%, lower limit of the 95% confidence interval=-13.11%; P noninferiority=0.005). PR was observed in 25 (80.6%) of 31 patients in the single-dose rituximab group and 26 (81.3%) of 32 patients in the cyclophosphamide group (P=0.95). The median time to PR was similar between two groups (23.0 days for rituximab group vs. 25.5 days for cyclophosphamide group, P=0.47). The median time to CR was 8 days shorter in the single-dose rituximab group than in the cyclophosphamide group, but with no statistically significant difference (28.0 days vs. 36.0 days, P=0.41). The median time for inhibitor titer to decrease by 50% of baseline also showed a shorter trend in the single-dose rituximab plus glucocorticoid group (8.0 days vs. 11.0 days, P=0.39). Subgroup analysis showed patients with high FVIII inhibitor titer (&amp;gt;20 BU/ml) were less likely and slower to achieve both CR and PR. The percentage of patients who experienced treatment-related adverse events (TRAEs) or grade 3 or 4 TRAEs were comparable between the rituximab and cyclophosphamide groups (58.1% vs. 37.5%, P=0.10 and 12.9% vs. 6.3%, P=0.43 respectively). Conclusion Single-dose rituximab plus glucocorticoid regimen showed similar efficacy and safety in this trial, without a reported risk of secondary malignancies or reproductive toxicity seen in cyclophosphamide, it might be recommended as a first-line therapy for AHA, especially in China where there is a young age trend in AHA patients.

Efficacy and Safety of Single-Dose Rituximab Biosimilar in the Initial Episode of Paediatric Steroid-Sensitive Nephrotic Syndrome

Efficacy and Safety of Single-Dose Rituximab Biosimilar in the Initial Episode of Paediatric Steroid-Sensitive Nephrotic Syndrome

#5386 ONCO-NEPHROLOGY: THE ROLE OF KIDNEY BIOPSY IN THE MANAGEMENT OF SIDE EFFECTS OF TARGETED THERAPIES

Abstract Background and Aims The introduction of innovative therapies, resulting from revisiting cancer as a disease of the immune system, has changed the scenario of complications. These new classes of drugs, such as targeted therapies and immune checkpoint inhibitors, assure substantial advantages in cancer therapy, despite some side affecting various organs, including the kidney. Histological evaluations of kidney disorders induced by targeted/immunotherapy are limited. Method In this study we examined the histological features of patients treated with new cancer agents who underwent kidney biopsy for new onset kidney failure and/or urinary abnormalities. Results The cohort included 30 adult patients. The most frequently administered therapies were immunotherapy (30%), targeted therapy (26.7%), immunotherapy plus targeted therapy (13.3%), immunotherapy plus chemotherapy (13.3%), targeted therapy plus chemotherapy (16.7%). The most common histological finding was tubular interstitial nephritis (30%) that was associated with acute tubular necrosis in 4 cases, and thrombotic microangiopathy (23.3%). After kidney biopsy, 16 of the 30 patients were treated according to the histological diagnosis. Fourteen patients were treated with steroids. One patient with membranous nephropathy was treated with a single dose of rituximab. A patient with severe thrombotic microangiopathy requiring dialysis received a treatment with eculizumab for 3 months. Overall some renal response was obtained in all patients treated with glucocorticoids, while complete kidney response was achieved in the patient treated with rituximab. Cancer treatment was resumed without change in 21 out of 30 patients. Conclusion Kidney biopsy is critical for the management of kidney toxicities and should be strongly encouraged for patients showing adverse kidney effects of novel cancer agents.

#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.

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.

Outcomes of ABO-incompatible liver transplantation in end-stage liver disease patients co-infected with hepatitis B and human immunodeficiency virus

Human immunodeficiency virus (HIV)-positive patients coinfected with hepatitis B virus (HBV) are eligible for liver transplantation (LT) in Africa and Southeast Asia, particularly China. However, the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT (ABOi-LT) is unknown. To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with end-stage liver disease (ESLD). We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT. The pretransplantation HIV viral load was undetectable, with no active opportunistic infections. Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses, followed by an intraoperative regimen of intravenous immunoglobulin, methylprednisolone, and basiliximab. Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil, and prednisone. At the intermediate-term follow-up, patients showed undetectable HIV viral load, CD4(+) T cell counts greater than 150 cells/μL, no HBV recurrence, and stable liver function. A liver allograft biopsy showed no evidence of acute cellular rejection. Both patients survived at 36-42 mo of follow-up. This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes, suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.

The need for kidney biopsy in the management of side effects of target and immunotherapy.

The introduction of innovative therapies, resulting from revisiting cancer as a disease of the immune system, has changed the scenario of complications. These new classes of drugs, such as targeted therapies and immune checkpoint inhibitors, assure substantial advantages in cancer therapy, despite some side effects affecting various organs, including the kidney. Histological evaluations of kidney disorders induced by targeted/immunotherapy are limited. In this study we examined the histological features of patients treated with new cancer agents who underwent a kidney biopsy for new onset kidney failure and/or urinary abnormalities. The cohort included 30 adult patients. The most frequently administered therapies were immunotherapy (30%), targeted therapy (26.7%), immunotherapy plus targeted therapy (13.3%), immunotherapy plus chemotherapy (13.3%), targeted therapy plus chemotherapy (16.7%). The most common histological finding was tubular interstitial nephritis (30%) that was associated with acute tubular necrosis in 4 cases, and thrombotic microangiopathy (23.3%). After kidney biopsy, 16 of the 30 patients were treated according to the histological diagnosis. Fourteen patients were treated with steroids. One patient with membranous nephropathy was treated with a single dose of rituximab. A patient with severe thrombotic microangiopathy requiring dialysis received a treatment with eculizumab for 3 months. Overall some renal response was obtained in all patients treated with glucocorticoids, while complete kidney response was achieved in the patient treated with rituximab. Cancer treatment was resumed without change in 21 out of 30 patients. Kidney biopsy is critical for the management of kidney toxicities and should be strongly encouraged for patients showing adverse kidney effects of novel cancer agents.

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

Double Filtration Plasmapheresis for Desensitization during Haploidentical Stem Cell Transplantation in Patients with Positive Donor-Specific Anti-HLA Antibodies

Background:Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. Plasma exchange (PE) is an effective treatment widely used for DSA desensitization. However, a large volume of plasma is required. Double filtration plasmapheresis (DFPP) is a semi-selective blood purification modality derived from the PE modality. DFPP avoids the unnecessary loss of plasma proteins, reduces the need for plasma and increases the efficiency of purification. To define the efficacy of DFPP for DSA-positive patients in HaploSCT, we conducted a nested case-control study. Methods: Patients who underwent HaploSCT in the Bone Marrow Transplantation Center of the First Affiliated Hospital of Zhejiang University School of Medicine from March 2017 to November 2021 were enrolled in the study cohort. Thirty-two patients with positive DSA (MFI≥2000) were treated with desensitization protocol including DFPP. Ninety-six patients (1:3) with negative DSA were randomly matched according to gender, age and transplantation time as the control group. DSA positive patients were given alternate-day DFPP twice before starting one week before the beginning of transplant conditioning. DSA was retested after DFPP treatment. A single dose of rituximab (375 mg/m2) was administrated after completion of DFPP. Results: A total of 32 HaploSCT patients with DSAs were included in the study. The majority of patients in the DSA group were female (75%) and a mean age of 41 (13-63) years . 96 DSA negative patients were selected as controls. The two groups had equivalent subject and donor characteristics, including age, gender, underlying diseases, conditioning regimens and GVHD prophylaxis.20 (62.5%) patients presented anti-HLA class I DSAs (4 of them with > 10000 MFI), 9 (28.1%) presented anti-HLA class II DSA (2 with > 10000 MFI) and 3 (9.3%) presented both anti-HLA class I and II DSA (1 with > 10000 MFI). After DFPP treatment, levels of DSA decreased significantly. The mean MFI values before and after treatment were 7189.56 ±4294.01 vs. 2869.57±3454.55 (P < 0.001), respectively. All patients in DSA group achieved hematopoietic reconstitution within 28 day of transplantation. The mean neutrophils and platelets engraftment time was 13.44±2.42 days and 14.03±3.78 days respectively, which were comparable to control group. In the DSA and control groups, the incidence of grade III-IV aGVHD was 9.37% vs. 10.41% (P < 0.05), the 2-year cumulative recurrence rate was 26.35% vs. 15.62% (P < 0.05) and the overall survival (OS) was 77.20% vs. 81.20% (P < 0.05), respectively. Conclusion: DFPP can significantly reduce the level of DSA in patients before transplantation. Treatment with DFPP and rituximab is effective in promoting engraftment for DSA-positive patients in HaploSCT.

Comparison of the efficacy and safety of 2 low-dose rituximab regimens in the second-line treatment of primary immune thrombocytopenia in children

Objective: To compare the efficacy and safety of 2 low-dose rituximab regimens in the treatment of children with primary immune thrombocytopenia (ITP). Methods: A total of 90 ITP children admitted to the Hematology Oncology Center of Beijing Children's Hospital from January 2018 to March 2021 were enrolled in this prospective cohort study. In the single-dose group, rituximab was given with a single dose of 375 mg/m2 (maximum dose 600 mg). In the 4-dose group, rituximab was given with a dose of 100 mg weekly (if body weight of the patient ≥ 30 kg, increase dosage to 200 mg weekly) for 4 weeks. Wilcoxon Mann-Whitney test, Chi-square test and Fisher's exact test were used to analyze the difference in efficacy, safety and treatment burden between two groups. Results: Among the 90 children, 41 were male and 49 were female, and the age of medication was 6.8 (4.1,10.0) years. There were 27 cases in the single-dose group and 63 cases in the 4-dose group.There were no significant differences in overall response rate, complete response rate and partial response rate between the single-dose group and 4-dose group (41% (11/27) vs. 33% (21/63), 26% (7/27) vs. 19% (12/63), 15% (4/27) vs. 14%(9/63), χ2=0.45, 0.54, 0.00, all P>0.05). The single-dose group was earlier to get overall response than the 4-dose group (1 (1, 1) vs. 3 (2, 6) weeks, Z=-3.24, P=0.001). There were no significant differences in the sustained response rate, the overall response rate in 1 year, the complete response rate in 1 year, and the partial response rate in 1 year between the single-dose group and the 4-dose group (33% (9/27) vs. 30% (19/63), 30% (8/27) vs. 24% (15/63), 19% (5/27) vs. 14% (9/63), 11% (3/27) vs. 10% (6/63), χ2=0.09, 0.34, 0.04, 0.00, all P>0.05). There were no significant differences in the duration of overall response, recurrence rate within half a year and one year, recurrence time and rate of adverse events between the single-dose group and 4-dose group (all P>0.05). The number of hospitalizations, the duration of hospital stays and the dosage of the single-dose group were significantly lower than those of the 4-dose group (1 (1, 1) vs. 4 (4, 4) times, 5 (4, 7) vs. 8 (5, 8) d, 400 (250, 500) vs. 400 (400, 800) mg, Z=-8.67, -3.03, -4.05, all P<0.05). Conclusions: The single-dose rituximab regimen is comparable to 4-dose rituximab regimen in effectiveness and safety for treatment of children ITP, but more economical and convenient. The single-dose rituximab regimen is more suitable for the second-line treatment of children ITP.

POS-138 COMPARATIVE STUDY BETWEEN SINGLE DOSE RITUXIMAB THERAPY VERSUS MULTIPLE DOSE REGIMEN IN IDIOPATHIC MEMBRANOUS NEPHROPATHY AND ITS CORRELATION WITH PERIPHERAL BLOOD CD19 COUNT

Idiopathic membranous nephropathy is a common cause of nephrotic syndrome in adult population and can lead to CKD if not treated properly. Conventional therapeutic options like Cyclophosphamide & CNI associated with significant toxicity & relapse rate. Though Rituximab is relatively safe multiple dose protocol leads to high cost burden. In this trial single dose Rituximab therapy has been compared with multiple dose regimen for this which will significantly cut down cost and drug related adverse effects.

213.4: Single-dose Rituximab Induction May Prevent EBV Viremia in Paediatric Kidney Recipients Long-term: An Investigation From the Nordic Paediatric Renal Transplantatioinn Study Group

213.4: Single-dose Rituximab Induction May Prevent EBV Viremia in Paediatric Kidney Recipients Long-term: An Investigation From the Nordic Paediatric Renal Transplantatioinn Study Group

P1333: PLASMA EXCHANGE, IMMUNOGLOBULIN &amp; PRE-TRANSPLANT IMMUNOSUPPRESSION: AN EFFECTIVE DESENSITISATION STRATEGY FOR DSA ALLOANTIBODIES IN HAPLOIDENTICAL HCT FOR PAEDIATRIC RED CELL DISORDERS

Background: Near universal availability of HCT is possible due to the feasibility of haploidentical transplantation [haplo HCT] with the use of post-transplantation cyclophosphamide or TCRαβ CD+19 depletion, enabling HCT for haemoglobinopathies and rare inherited anaemias for whom donors are underrepresented in registries. Patients with these disorders are at increased risk of developing anti-HLA antibodies having often received multiple transfusions pre-transplantation. HLA antibodies constituting donor specific antigens [DSA] affect approximately 15% of haplo HCT [Leffel, 2013] representing a significant cause of primary graft failure [Ciurea, 2009]. An effective desensitisation strategy is necessary as alternative donors for haploidentical HCT are often lacking. Several desensitisation approaches have been developed based on strategies used for solid organ transplantation, yet there exists no consensus in their application to haplo HCT for paediatric haemoglobinopathies where there is a particularly high risk of graft failure [de la Fuente, BBMT 2019, de la Fuente, ASH 2020]. Aims: To assess the efficacy of plasma exchange, high dose immunoglobulin and pre-transplant immunosuppression as a desensitisation strategy for DSA alloantibodies in paediatric patients undergoing haploidentical HCT for red cell disorders. Methods: Seven [17.5%] patients were found to have HLA class I DSA in 40 consecutive related reduced-intensity conditioning haplo HCT with post-transplant cyclophosphamide for red cell disorders performed at St Mary’s Hospital from 2013 to December 2021. The MFI cut off used was 2,000U. Transplant indications included homozygous sickle cell disease [n=5], HbSβ0 thalassaemia [n=1] and Diamond-Blackfan anaemia [n=1]. Median age was eight years [range 3-15 years]. Five children were female. Two patients had two different DSA. Each patient received a regimen based on the John Hopkins protocol [Leffel, 2013], comprising a single dose of rituximab 375mg/kg, four alternate day cycles of single volume plasmapheresis [replacing 100% volume with 5% albumin] and anti-CMV hyperimmune immunoglobulin 100mg/kg on days -16, -14, -12 and -10 before the initiation of the conditioning regimen and a further cycle of single volume plasmapheresis on D -1 and anti-CMV hyperimmune immunoglobulin 100mg/kg, and immunosuppression with tacrolimus and MMF to Day 0. HLA antibodies were measured on Day 0 prior to HSC infusion. If the MFI had not decreased <2000U, two further cycles of single volume plasmapheresis and anti-CMV hyperimmune immunoglobulin 100mg/kg were given on D+1 and D+2. Results: The median MFI at baseline was 5,974 U [range 1,544-22806U]. The protocol was well tolerated and completed without serious adverse events in all patients. Four patients required additional cycles on days +1 and +2. Median MFI at protocol completion was 230U [range 0-769U]. No patient suffered primary graft failure. Median time to neutrophil engraftment was 21 days [range 15-24]. All patients achieved full donor whole blood chimerism on D+28 and wheras there was mixed chimerism in the T cell fraction in three of the patients, this improved over time in all patients and no patient suffered secondary graft failure. Summary/Conclusion: The use of a desensitisation protocol comprising the combination of plasma exchange, high dose immunoglobulin and pre transplant immunosuppression constitutes an effective desensitisation strategy for DSA and abrogates the risk of graft failure in multiply transfused paediatric patients undergoing haploidentical HCT for red cell disorders, enabling HCT where no alternative donor exists.

Use of rituximab in SARS-CoV-2-positive renal transplant recipient with EBV reactivation and probable haemophagocytic lymphohistiocytosis

We present a case of a rapid clinical recovery in a critically ill kidney transplant recipient with SARS-CoV-2 positivity, Epstein–Barr virus (EBV) reactivation and probable secondary hemophagocytic lymphohistiocytosis (HLH) treated with etoposide-free regimen, based on dexamethasone and a single dose of rituximab. Although rituximab is often a part of EBV-HLH treatment strategy, its use in simultaneous Coronavirus 2019 disease (COVID-19) and solid-organ transplantation has not been reported yet. We review the current evidence for the potential of SARS-CoV-2 to trigger EBV reactivation, leading to a severe clinical illness. Finally, we compare the clinical features of hyper-inflammatory response typical for severe COVID-19 and classical secondary HLH and discuss the benefits of therapeutic B-cell depletion in both conditions.

Low-dose rituximab in immune thrombocytopenia: One and done.

Rituximab is a widely-used medication for many years, important in management of immune thrombocytopenia (ITP); however, the optimal rituximab dose remains unknown. Ni and colleagues report a clinical trial comparing 2 doses of rituximab: a single dose of 375 mg/m2 versus 100 mg/m2 weekly for four weeks. The authors report similar efficacy and safety profile with both strategies. However, single-dose rituximab offered substantial benefits in quality-of-life and decrease in treatment costs. The study by Ni and colleagues adds a new option for management of ITP with rituximab. This article is protected by copyright. All rights reserved.

Hepatocellular carcinoma and cancer-related mortality after kidney transplantation with rituximab treatment.

PurposeThere are increased therapeutic usages of rituximab in kidney transplantation (KT). However, few studies have evaluated the effect of rituximab on cancer development following KT. This study aimed to evaluate the effect of rituximab on the cancer occurrence and mortality rate according to each type of cancer.MethodsFive thousand consecutive recipients who underwent KT at our center were divided into era1 (1990–2007) and era2-rit– (2008–2018), and era2-rit+ (2008–2018) groups. The era2-rit+ group included patients who received single-dose rituximab (200–500 mg) as a desensitization treatment 1–2 weeks before KT.ResultsThe 5-year incidence rates of malignant tumors after KT were 3.1%, 4.3%, and 3.5% in the era1, era2-rit–, and era2-rit+ group, respectively. The overall incidence rate of cancer after transplantation among the 3 study groups showed no significant difference (P = 0.340). The overall cancer-related mortality rate was 17.1% (53 of 310). Hepatocellular carcinoma (HCC) had the highest mortality rate (61.5%) and relative risk of cancer-related death (hazard ratio, 8.29; 95% confidence interval, 2.40–28.69; P = 0.001). However, we found no significant association between rituximab and the incidence of any malignancy.ConclusionOur results suggest that single-dose rituximab for desensitization may not increase the risk of malignant disease or cancer-related mortality in KT recipients. HCC was associated with the highest risk of cancer-related mortality in an endemic area of HBV infection.

Incidence and risk factors of rituximab-associated hypogammaglobulinemia in patients with complicated nephrotic syndrome.

Hypogammaglobulinemia is a major adverse event after rituximab treatment; however, the precise incidence and risk factors are unclear in complicated steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS) patients. This was a single-center, retrospective, observational study. Patients who received a single dose of rituximab for complicated SDNS or FRNS between February 2007 and May 2019 were enrolled. Serum IgG levels were plotted, and their trends were evaluated after rituximab treatment. The incidence of transient and persistent hypogammaglobulinemia was examined, and risk factors were calculated by multivariate analysis using logistic regression. We enrolled 103 patients who received 238 single doses of rituximab. Hypogammaglobulinemia was observed in 58.4% of the patients at least once after a single dose of rituximab treatment and 22.3% developed persistent hypogammaglobulinemia. Serum IgG levels gradually increased during B-cell depletion, and patients with low serum IgG levels at rituximab treatment had persistent hypogammaglobulinemia. Repeated courses of rituximab treatment increased the incidence of hypogammaglobulinemia. A past history of steroid-resistant nephrotic syndrome (SRNS) (odds ratio [OR] = 10.02; 95% confidence interval [CI] = 2.65-37.81; P < 0.001) and low serum IgG levels at rituximab treatment (OR = 7.63; 95% CI = 2.10-27.71; P = 0.002) was significantly associated with hypogammaglobulinemia in multivariate analysis. Hypogammaglobulinemia is a frequent adverse event after rituximab treatment, although IgG levels slightly increase during B-cell depletion. Low serum IgG levels at rituximab treatment and a past history of SRNS are significant risk factors for the development of hypogammaglobulinemia after rituximab treatment.