Disseminated Enteroviral Infection Associated with Obinutuzumab

Two cases of disseminated enteroviral infection occurred in patients who received the CD20 monoclonal antibody obinutuzumab. Clinical features included hepatitis, edema, and a dermatomyositis-like syndrome. These manifestations may be unfamiliar to clinicians and are possibly responsive to intravenous immunoglobulin. Clinicians should remain vigilant for enteroviral infections in patients receiving obinutuzumab.     

1例重症幼年皮肌炎患儿的药学监护

目的探讨临床药师在重症幼年皮肌炎患儿药学监护中的作用。方法临床药师参与1例重症幼年皮肌炎患儿治疗方案的制定,对患儿幼年皮肌炎治疗、抗感染治疗进行疗效监护,并监护患儿的肝肾功能、电解质和感染情况,根据患儿病情提供个体化给药方案建议。结果与结论患儿病情稳定,皮肌炎治疗有效,抗感染治疗有效,等渗脱水、低钙血症、低钾血症得到纠正,肝肾功能损害没有进一步加重。临床药师参与个体化治疗方案的制定,为医护和患儿提供药学服务,促进了临床用药的安全性、有效性和合理性。     

Persistent viral shedding of severe acute respiratory syndrome coronavirus 2 after treatment with bendamustine and rituximab: A case report

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is detectable in nasopharyngeal specimens for up to 12–20 days regardless of the presence of chronic diseases in patients. We report a case of prolonged SARS-CoV-2 infection that lasted for more than eight weeks. The patient had persistent lymphopenia after receiving six cycles of bendamustine and rituximab (BR) therapy for follicular lymphoma; the last chemotherapy session was completed nine months before admission. The first nasopharyngeal specimen (NPS) for the SARS-CoV-2 polymerase chain reaction assay tested positive for the N501Y variant five weeks before admission. The patient's general and respiratory conditions gradually worsened; therefore, he was admitted to our hospital, and the same SARS-CoV-2 variant was subsequently identified on admission. Treatment for coronavirus disease was initiated, and the patient's condition improved; however, the NPS tested positive on day 15. The patient was discharged on day 28 and was instructed to isolate at home for a month. Hence, possible prolonged SARS-CoV-2 shedding should be considered in patients who receive BR therapy.     

The promising role of monoclonal antibodies for immunotherapy of the HIV-associated cancer,non-Hodgkin lymphoma

Association between HIV/AIDS and some of the cancers such as lymphomais is well known. Relative risk for developing non-Hodgkin lymphoma (NHL) increases 60–200 folds in HIV-infected individuals. Diffuse large B cell lymphoma (DLBCL), primary effusion lymphoma (PEL), Burkitt's lymphoma (BL) and Plasmablastic Lymphoma (PBL) are among the most frequent subtypes. During the last century, scientists found that the immune system could potentially detect and destroy cancer cells. Therefore, they started a new field of study, which is named immunotherapy. There are different immunotherapeutic methods, among which therapeutic antibodies, such as Brentuximabvedotin (Adcetris), Ibritumomabtiuxetan (Zevalin) and rituximab (Rituxan), used for treatment of NHLs showed promising results. In this article, we will review the immunotherapeutic option, monoclonal antibodies, for treatment of HIV-associated NHLs as well as their recent clinical status. We will also discuss the selective monoclonal antibody for each subtype of NHLs.     

Preformed donor-reactive T cells that persist after ABO desensitization predict severe T cell-mediated rejection after living donor kidney transplantation – a retrospective study

Preformed donor-reactive T cells are relatively resistant to standard immunosuppression and account for an increased incidence of T cell-mediated rejection (TCMR) and inferior kidney allograft outcomes. We analyzed 150 living donor kidney transplant recipients (KTRs) of a first kidney allograft. Ninety-eight ABO-compatible (ABOc) and 52 ABO-incompatible (ABOi) KTRs were included. Samples were collected at 6 time points, before rituximab, before immunoadsorption and pretransplantation, at +1, +2, and +3 months posttransplantation, and donor-reactive T cells were measured by interferon-γ ELISPOT assay. Twenty of 98 ABOc (20%) and 12 of 52 ABOi KTRs (23%) showed positive pretransplant ELISPOT. Eight of 20 ABOc-KTRs (40%) with positive pretransplant ELISPOT showed TCMR, whereas 17 of 78 ABOc-KTRs (22%) with negative pretransplant ELISPOT did (P = 0.148). Seven of 12 ABOi KTRs (57%) with positive pretransplant ELISPOT showed TCMR, whereas only 3 of 40 ABOi KTRs (8%) with negative pretransplant ELISPOT did (P < 0.001). Interestingly, 6 of 7 ABOi KTRs with positive pretransplant ELISPOT that persists after ABO desensitization developed TCMR. Among 118 KTRs with negative pretransplant ELISPOT, 10 of 72 ABOc-KTRs (14%), but 0 of 46 ABOi KTRs, developed positive posttransplant ELISPOT (P = 0.006). Preformed donor-reactive T cells that persist despite ABO desensitization identify KTRs at highest risk of TCMR. Less de-novo donor-reactive T cells after ABO desensitization may account for less TCMR. Both, the use of rituximab and early initiation of calcineurin inhibitor-based maintenance immunosuppression may contribute to these findings.     

非霍奇金淋巴瘤患者利妥昔单抗化疗后肺部并发症的特点及对生存率的影响

目的:探讨非霍奇金淋巴瘤（non-Hodgkin' s lymphoma,NHL）患者接受利妥昔单抗化疗后肺部并发症的发生率、发病特点及对生存率的影响。方法:收集2011年1月至2016年6月在我院接受含利妥昔单抗方案化疗的163例NHL患者作为研究对象,观察患者肺部并发症的发生率、发病特点,采用单因素与多因素分析观察肺部并发症与患者3年死亡率的相关性。结果:163例患者中共37例患者发生64例次呼吸系统并发症,并发症发生率为22.70％。肺部并发症和无肺部并发症患者性别、年龄、体质量指数、NHL类型、NHL分期、左心室射血分数、利妥昔单抗总剂量相比较差异均无统计学意义（P＞0.05）,肺部并发症患者肺/胸膜受累患者百分率高于无肺部并发症患者,差异有统计学意义（P＜0.05）。患者3年生存率为80.98％。单因素和多因素分析均显示,肺部并发症是影响NHL患者预后的风险因素（P＜0.05）。结论:NHL接受利妥昔单抗化疗后肺部并发症与患者3年死亡风险增加相关。     

A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B-cell lymphoma

Polatuzumab vedotin (pola) is a CD79b-targeted antibody-drug conjugate delivering a potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open-label, single-arm study of pola 1.8 mg/kg, bendamustine 90 mg/m², rituximab 375 mg/m² (pola + BR) Q3W for up to six cycles in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who received ≥1 prior line of therapy and were ineligible for autologous stem cell transplantation (ASCT) or experienced treatment failure with prior ASCT. Primary endpoint was complete response rate (CRR) at the end of the treatment (EOT) by positron emission tomography–computed tomography (PET-CT) using modified Lugano Response Criteria. Secondary endpoints included efficacy, safety, and pharmacokinetics. Thirty-five patients (median age 71 [range 46-86] years) were enrolled. Twenty-three (66%) patients had refractory disease, and 23 (66%) had ≥2 prior lines of therapy. At a median follow-up of 5.4 (0.7-11.9) months, patients received a median of five treatment cycles. CRR was 34.3% (95% confidence interval [CI] 19.1-52.2) at EOT. Overall response rate was 42.9% at EOT, and median progression-free survival was 5.2 months (95% CI 3.6-not evaluable). Median overall survival was not reached. No fatal adverse events (AEs) were observed. Grade 3-4 AEs were mainly hematological: anemia (37%), neutropenia (31%), white blood cell count decreased (23%), thrombocytopenia/platelet count decreased/neutrophil count decreased (20% each), and febrile neutropenia (11%). Grade 1-2 peripheral neuropathy (PN; sensory and/or motor) was reported in 14% of patients; there were no ≥grade 3 PN events. This study (JapicCTI-184048) demonstrated the efficacy and safety of pola + BR in Japanese patients with R/R DLBCL who were ineligible for ASCT.     

Consolidation with 90Yttrium‐ibritumomab tiuxetan after bendamustine and rituximab for relapsed follicular lymphoma

Bendamustine and rituximab (BR) are widely used in patients with follicular lymphoma (FL) previously treated with conventional immunochemotherapy, but the role of consolidation radioimmunotherapy in these patients is unknown. This study evaluated the efficacy and safety of consolidation with ⁹⁰Yttrium‐ibritumomab tiuxetan (⁹⁰Y‐IT) after re‐induction therapy with BR in patients with previously treated FL. This study included adult patients with relapsed FL who had undergone one or two prior therapies. Re‐induction therapy with BR was administered every 4 weeks up to 4–6 cycles. If patients achieved at least partial response, ⁹⁰Y‐IT was administered as consolidation therapy. The primary endpoint was 2‐year progression‐free survival (PFS) after consolidation. A total of 24 FL patients (median age 60 years) who had undergone one (n = 17) or two (n = 7) prior treatments received BR. After BR therapy, 22 patients proceeded to consolidation with ⁹⁰Y‐IT, resulting in an overall 88% response rate to the protocol treatment. Within a median observation period of 46.8 months, the estimated 2‐year PFS rate after the consolidation among the 22 patients receiving ⁹⁰Y‐IT was 59% (95% confidence interval [CI], 38%–77%). Patients whose remission after previous treatment had lasted ≥2 years had a significantly higher 2‐year PFS rate than patients whose remission after previous treatment had been <2 years (68% vs. 33%, Wilcoxon p = 0.0211). Major adverse events during the protocol treatment and within 2 years after the consolidation were hematological toxicities, but they were generally acceptable. Consequently, the estimated 2‐year overall survival after the consolidation was 95% (95% CI, 74%–99%). In conclusion, in a subset of patients with previously treated FL, ⁹⁰Y‐IT consolidation after BR re‐induction conferred a durable remission, indicating that consolidation therapy using ⁹⁰Y‐IT may be a novel therapeutic option for patients with relapsed FL (UMIN000008793).     

Successful treatment of relapsing autoimmune thrombotic thrombocytopenic purpura with rituximab

Thrombotic thrombocytopenic purpura (TTP) is a rare but life‐threatening condition characterized by thrombotic microangiopathy. The standard treatment for TTP is plasmapheresis. For refractory or relapsing cases, various immunosuppressive agents have been tried, and among them rituximab has shown promising results. TTP is rarer in the pediatric age group and the use of rituximab in children with TTP is limited. Reported herein is the successful treatment of relapsing autoimmune TTP with rituximab in a 12‐year‐old girl.