ABO 혈액형 부적합 신장이식에서 Rituximab의 고용량 투여군과 저용량 투여군의 효과 및 안전성 비교 분석

문정은,김효진,김재송,손은선 한국병원약사회 2017 병원약사회지 Vol.34 No.2

Background : ABO incompatible (ABOi) kidney transplantation has become an effective option to resolve organ shortage. In Korea, in 2015, the number of patients who received kidney transplantation was 1,891; among them, the number of ABOi kidney transplantation was 450. To ensure successful ABOi kidney transplantation, rituximab is used to reduce acute antibody-mediated rejection (AMR). However, the adequate rituximab dosage in ABOi kidney transplantation remains undetermined; therefore, this study aimed to evaluate the effective dose of rituximab. Methods : From July 2012 to June 2015, we conducted a chart review in a total of 53 ABOi kidney transplantation recipients, who took rituximab before the transplantation at Severance Hospital. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, and corticosteroids. The pre-conditioning protocol included double-filtration plasmapheresis and a single dose of rituximab. We classified the study population into two groups, i.e., the high dose rituximab group (375 mg/m2 rituximab, n=27) and the low dose rituximab group (200 mg/body rituximab, n=26). Information on the incidence of AMR, infection and neutropenia, reduction of anti A/B antibody titer, peripheral CD19 and CD20 levels, and population characteristic were collected from the medical records. Results : The incidence of AMR was 7.4% in the high dose rituximab group vs. 15.4% in the low dose rituximab group (P=0.42). Effective reduction of the anti A/B antibody titer and elimination of the peripheral blood CD19 and CD20 levels were observed in both groups. However, the infectious complications and incidence of late onset neutropenia (LON) were more common in the high dose rituximab group (29.6% vs. 15.4%, P=0.22; 40.7% vs. 0.0%, P 0.001). Conclusion : The results were similar in patients in the low dose rituximab group as compared to patients in the high dose rituximab group. These results suggested that the low dose of rituximab(200 mg/body) is sufficient in cases with ABOi kidney transplantation.

Real world data on follicular lymphoma patients treated by rituximab-containing immunochemotherapy and rituximab maintenance

( Hee Kyung Kim ),( Wonseok Kang ),( Dong Hyun Sinn ),( Joon Hyeok Lee ),( Won Seog Kim ),( Seok Jin Kim ) 대한내과학회 2020 The Korean Journal of Internal Medicine Vol.35 No.1

Background/Aims: Real-world data about the treatment outcomes of patients receiving rituximab-containing immunochemotherapy followed by rituximab maintenance are required to understand better the treatment for follicular lymphoma (FL). Methods: A cross-sectional study analyzed FL patients who were treated with R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and rituximab maintenance. Results: Of 139 patients, 85 patients received R-CVP and 54 received R-CHOP. The characteristics did not differ significantly between the groups. Only grade 3 of FL was more common in R-CHOP. The complete response rate did not differ significantly between R-CHOP (50/54, 92.6%) and R-CVP (77/85, 90.6%). The number of disease relapses during rituximab maintenance did not differ significantly between the groups (p = 0.798). Therefore, the comparison of progression-free survival (PFS) showed no significant difference: the 3-year PFS rates for R-CVP and R-CHOP were 77% and 85%, respectively (p = 0.567). Although five of 56 hepatitis B virus (HBV) core antibody (anti-HBc)-positive patients experienced HBV reactivation, all cases of HBV reactivation were identified during regular monitoring for HBV DNA in blood, and were successfully managed with antiviral treatment. Conclusions: The survival outcomes of FL patients on rituximab maintenance after responding to R-CVP or R-CHOP were similar. Rituximab-containing immunochemotherapy followed by rituximab maintenance can be safely used for anti-HBc-positive patients if HBV DNA titer in blood can be regularly monitored.

Adjuvant rituximab treatment for pemphigus: a retrospective study of 45 patients in a single-center with long-term follow-up

( Seh Hyun Park ),( Tae Hyung Kim ),( Yuri Choi ),( Sang Eun Lee ),( Soo Chan Kim ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Pemphigus is a potentially life-threatening autoimmune bullous disease. Rituximab is one of the most effective therapeutic agents for treating pemphigus. Objectives: We aimed to evaluate the clinical response and relapse rate of rituximab in the treatment of pemphiguswith long-term follow-up. We also evaluated the success of repeated cycles of rituximab to treat relapse. Methods: A total of 45 patients with pemphigus who were treated with at least 1 cycle of 2 infusions of rituximab (375 mg/m2 per infusion weekly) were retrospectively studied. All the patients were followed up for more than 2 years and up to 8 years after first rituximab cycle. Results: Overall, all 45 patients (100%) achieved complete or partial remission within 8 months from the first treatment cycle. Thirty-four (76%) patients relapsed at median time of 17 months. All the patients who received additional cycles of rituximab after relapse achieved new remission. A serious adverse event attributed to rituximab treatment occurred in 1 patient who was excluded from the end-point analysis, in the form of acute respiratory distress syndrome. Conclusion: Rituximab is effective and safe for the induction and maintenance of remission in patients with pemphigus. Relapses can be frequent with long-term follow-up but can be managed with retreatment of rituximab.

Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing

Min Ji Jeon,Eun Sang Yu,Chul Won Choi,Dae Sik Kim 대한내과학회 2023 The Korean Journal of Internal Medicine Vol.38 No.6

Background/Aims: Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge. Methods: We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing. Results: In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus- PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. Conclusions: We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.

Impact of pretransplant rituximab induction on highly sensitized kidney recipients

Young Hae Song,Kyu Ha Huh,Yu Seun Kim,Hyung Soon Lee,Myoung Soo Kim,Soo Jin Kim,Hyun Jung Kim,Soon Il Kim,Dong Jin Joo 대한외과학회 2012 Annals of Surgical Treatment and Research(ASRT) Vol.82 No.6

Purpose: Highly sensitized patients with a high level of panel reactive antibody (PRA) experience more episodes of antibody-mediated rejection (AMR) and poorer graft survival than non-sensitized patients. Rituximab is a well-known monoclonal anti-CD20 antibody that causes the depletion of B lymphocytes. The aim of this study was to compare a rituximab-administered and a non-administered group of highly sensitized recipients. Methods: Forty-three kidney recipients with a PRA level of ≥50% were included. Sixteen (group R) received one dose of rituximab at 2 days prior to transplantation and 27 patients (group NR) did not. Results: Patients’ demographics, such as age, sex, dialysis duration, and type of immunosuppressive agent were not different in the two groups. No side effects due to rituximab administration were observed in group R. Class I PRA of group R (75.6 ± 37.7%) was higher than that of group NR (45.7 ± 35.8%, P = 0.013). More acute rejection episodes occurred within 1 year after transplantation in group NR but the difference between the groups was not significant (18.8% in group R vs. 29.6% in group NR, P = 0.631). However, two AMR episodes occurred only in group NR. Renal functions were not different in the two groups. In group R, CD19 and CD20 rapidly decreased 2 days after rituximab infusion. Furthermore, the administration of rituximab was not linked to acute rejection. Conclusion: To confirm the long-term anti-rejection and beneficial effects of rituximab, further studies should be performed with a larger cohort. In conclusion, rituximab administration 2 days prior to transplantation is both effective and safe.

[P137] Interstitial pneumonia in a patient with recalcitrant pemphigus vulgaris treated with rituximab

( Jae Won Lee ),( Yeong Joo Oh ),( Do Young Kim ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.1

Rituximab, an anti-CD20 B-cell depleting monoclonal antibody, has been shown to be a safe and effective treatment for refractory pemphigus vulgaris(PV). A 56-year-old man with refractory PV received rituximab(two weekly infusions of 1000mg) in combination with systemic steroids. Flow cytometry analysis followed by rituximab infusions showed complete depletion of CD20-positive cells. Although the lesions gradually improved, the patient presented fever, dyspnea and generalized weakness one month after the first infusion of rituximab. Chest CT revealed multifocal ground glass opacities in both lungs. PCR assay of whole blood showed significantly increased cytomegalovirus(CMV) DNA without other bacterial or viral pathogens detected in sputum. Fever and dyspnea resolved with intravenous antibiotics along with oral steroids and the patient is under evaluation by pulmonary department. The temporal onset of interstitial pneumonia following rituximab infusions strongly implicates exposure to rituximab as the trigger. Rituximab-induced interstitial lung diseases including acute respiratory distress syndrome, organizing pneumonia and pneumonitis are very rare with most of the knowledge coming from case reports but dermatologists should perceive this rare but potentially serious complication.

FCT 8 : Adjuvant Rituximab Therapy of Pemphigus: A retrospective study of 56 patients in a single-center

( Yuri Choi ),( Hye Rang On ),( Soo Chan Kim ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: Pemphigus is an acquired, rare, chronic, debilitating, and potentially life-threatening autoimmune vesiculobullous disorder that is characterized by mucocutaneous erosions or blisters. Without treatment, such blistering eventually leads to erosions in the skin, resulting in significant mortality. Objectives: This study was conducted to evaluate the efficacy and safety of repeated and prolonged B cell depletion with rituximab for the induction and maintenance of long-term remission in patients with pemphigus vulgaris(PV) or pemphigus foliaceus(PF). Methods: We conducted a single-center observational study of all patients with pemphigus treated with at least 2 courses of Rituximab between January 1, 2006 and July 31, 2013. Results: Fifty-six patients (median age 46 years (22-82 years) with PV (n=47) or PF (n=9) received at least 2 courses of Rituximab to achieve remission or to treat relapses. Overall, 55(98%) of 56 patients achieved remissions at some point during their follow-up. Of 55 patients with complete or partial remission after the initial infusions, 23(42%) patients had one more relapses during a follow-up time of 11 to 56 months. Of 23 patients with relapse, 13 patients received the second infusions of rituximab but 10 patients were treated without rituximab. Conclusion: Rituximab appeared to be effective and safe for the induction and maintenance of remission in patients with pemphigus. Patients treated with additional rituximab may have earlier remission after relapse.

Long-term survival of patients with bullous pemphigoid after rituximab treatment

( Dae San Yoo ),( Ji Hye Lee ),( Soo-chan Kim ),( Jong Hoon Kim ) 대한피부과학회 2020 대한피부과학회 학술발표대회집 Vol.72 No.1

Background: Bullous pemphigoid (BP) is one of the most common autoimmune bullous diseases. Rituximab, a monoclonal antibody targeting CD20, has been used in patients with refractory BP and has been demonstrated to be effective in rapidly achieving remission. However, long-term survival of BP patients receiving rituximab remains unknown. Objectives: To evaluate long-term survival and clinical outcome of BP patients treated with rituximab and to identify prognostic factors associated with survival. Methods: A retrospective cohort study was conducted on 52 patients diagnosed with BP treated with rituximab therapy between 2017 and 2020 at Gangnam Severance Hospital. We compared this cohort with our previous cohort from the published study in BP patients treated with conventional therapy without rituximab. Results: Of 52 patients, 37 patients have been given two doses of rituximab with 1,000 mg at 2-week intervals. Remission rate is 75.7% and the median time to remission was 5.4 months. The 1-, 2-, and 5-year mortality rates were 11%, 18%, and 35% which were lower than the previous cohort showing 19%, 29%, and 58%, respectively, but statistical significance of mortality between two cohorts was not seen. Dementia, neurologic diseases and failure of remission were associated with increased mortality in multivariate analysis. Conclusion: Rituximab can increase long-term survival and clinical efficacy in patients with BP.

Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study

( Dong Won Baek ),( Han-seung Park ),( Sang Kyun Sohn ),( Dae Young Kim ),( Inho Kim ),( Jae-sook Ahn ),( Young Rok Do ),( Se Ryeon Lee ),( Hyeon-seok Eom ),( Won-sik Lee ),( Sung-hyun Kim ),( Ho Sup 대한내과학회 2023 The Korean Journal of Internal Medicine Vol.38 No.5

Background/Aims: We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). Methods: Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. Results: In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. Conclusions: The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials.gov NCT01429610).

Rituximab 지연성과민반응에 대한 신속 탈감작 적용 1예

이수호,이재하,김남희,강동윤,이주연,정수지,오지현,강혜련 대한 소아알레르기 호흡기학회 2019 Allergy Asthma & Respiratory Disease Vol.7 No.2

Rituximab is a monoclonal antibody used for the treatment of B-cell malignancies, including diffuse large B-cell lymphoma. Infusion-related hypersensitivity reactions to rituximab is well known, and delayed hypersensitivity reactions to rituximab are also reported. Desensitization is commonly used to prevent immediate hypersensitivity reactions, but recently there have been cases of successful desensitization therapy for delayed hypersensitivity reactions. A 66-year-old patient who underwent rituximab treatment for diffuse large B-cell lymphoma showed repeated rituximab-induced delayed hypersensitivity reactions with whole body rashes. Intravenous rapid desensitization was performed by using a 1-bottle, 11-step protocol for 6 cycles and thereafter hypersensitivity reaction did not recur. We herein reported a case of delayed hypersensitivity reaction caused by rituximab, which was successfully desensitized using our 11-step protocol.