利妥昔单抗治疗温抗体自身免疫性溶血性贫血的疗效评价

目的评价利妥昔单抗治疗温抗体自身免疫性溶血性贫血(WAIHA)的临床疗效。方法选择2012年1月10日至2013年12月30日在我院被诊断为WAIHA的160例患者为研究对象,随机分为试验组(80例)和对照组(80例)。试验组接受375 mg/m2利妥昔单抗,1次/周,连续4周,对照组接受同等体积的生理盐水进行治疗。随访12个月后进行数据统计分析。结果试验组的完全缓解率(65%)高于对照组(35%),1年复发率(10%)低于对照组(50%),两组比较差异有统计学意义(P<0.05)。结论利妥昔单抗治疗WAIHA可以提高患者的完全缓解率,降低患者的复发率。     

Recent advances in the management of autoimmune pancreatitis in the era of artificial intelligence

Autoimmune pancreatitis (AIP) is a type of immune-mediated pancreatitis subdivided into two subtypes, type 1 and type 2 AIP. Furthermore, type 1 AIP is considered to be the pancreatic manifestation of the immunoglobulin G4 (IgG4)-related disease. Nowadays, AIP is increasingly researched and recognized, although its diagnosis represents a challenge for several reasons: False positive ultrasound-guided cytological samples for a neoplastic process, difficult to interpret levels of IgG4, the absence of biological markers to diagnose type 2 AIP, and the challenging clinical identification of atypical forms. Furthermore, 60% and 78% of type 1 and type 2 AIP, respectively, are retrospectively diagnosed on surgical specimens of resected pancreas for suspected cancer. As distinguishing AIP from pancreatic ductal adenocarcinoma can be challenging, obtaining a definitive diagnosis can therefore prove difficult, since endoscopic ultrasound fine-needle aspiration or biopsy of the pancreas are suboptimal. This paper focuses on recent innovations in the management of AIP with regard to the use of artificial intelligence, new serum markers, and new therapeutic approaches, while it also outlines the current management recommendations. A better knowledge of AIP can reduce the recourse to surgery and avoid its overuse, although such an approach requires close collaboration between gastroenterologists, surgeons and radiologists. Better knowledge on AIP and IgG4-related disease remains necessary to diagnose and manage patients.     

Spontaneous bacterial peritonitis from Salmonella: an unusual bacterium with unusual presentation

Spontaneous bacterial peritonitis (SBP) is a common cause of morbidity and mortality in patients with advanced cirrhosis and portal hypertension. While gram-negative rods and Enterococcus species are the common offending organisms, Salmonella has also been recognized as a rare and atypical offending organism. Atypical features of Salmonella SBP include both its occurrence in cirrhotic patients with immunosuppressive state and its lack of typical neutroascitic response. Diagnosis is often delayed as it requires confirmation from ascitic fluid culture. We report a case of Salmonella SBP occurring in a patient with decompensated cryptogenic cirrhosis with concurrent low-grade non-Hodgkin lymphoma and prior treatment with rituximab. Physicians should be aware of the atypical presentation, especially in cirrhotic patients who are immunosuppressed.     

Białaczka włochatokomórkowa oporna na standardową terapię analogiem puryn – opis przypadku i przegląd piśmiennictwa

Hairy cell leukemia (HCL) is a rare, chronic lymphoproliferative disorder. Currently, purine nucleoside analogs (PNA) constitute the first line treatment of HCL. Cladribine could induce long lasting remission in majority of patients with only a single cycle of therapy. In fact the relapsed patients could be treated successfully with cladribine too. Sometimes we observe the resistance to PNA. Rituximab and chemoimmunotherapy (rituximab plus cladribine) are effective in treatment of refractory HCL.We present a case of a 64-year-old man who was treated with rituximab after second progression of HCL. In March 2011, rituximab was given at a dose of 375 mg/m² i.v. once a week for eight weeks, with result of achievement of PR. During the last hospitalization in March 2013 the persistence of PR was confirmed.     

HLA-C Matching Status Does Not Affect Rituximab-Mediated Antibody-Dependent Cellular Cytotoxicity by Allogeneic Natural Killer Cells

Risk of leukemia relapse after T cell-depleted hematopoietic stem cell transplantation is lower in the “HLA-C mismatched” recipient-donor combinations. This might be attributable to increased natural killing by allogeneic NK cells carrying a KIR that does not bind to HLA-C on target cells (HLA-C-uncoupled KIR). Considering a new strategy of allogeneic NK cell transfer with rituximab to treat B-cell lymphomas, however, it is unknown whether the HLA-C matching status also affects rituximab-mediated antibody-dependent cellular cytotoxicity (ADCC). To address this issue, we investigated the levels of ADCC by purified NK cells carrying an HLA-C-uncoupled KIR, where the NK cell donors had either matched or mismatched HLA-C combination with target cells. Purified NK cells carrying an HLA-C-uncoupled KIR consistently showed enhanced ADCC against target cells when NK cell donors had an HLA-C-mismatch. When NK cell donors did not have an HLA-C mismatch, it was inconsistent whether HLA-C-uncoupled KIR caused ADCC enhancement. When the levels of ADCC by whole NK cells were compared, there were substantial differences among the donors regardless of the HLA-C matching status. Subjects with HLA-C mismatch may not have an advantage when cytoimmunotherapy using allogeneic NK cells is considered in combination with rituximab.     

B cell elimination in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus.     

R+DA-EPOCH方案治疗弥漫大B细胞淋巴瘤的疗效

目的 探讨R+DA-EPOCH方案治疗弥漫大B细胞淋巴瘤（DLBCL）的临床疗效和安全性。方法 选择2015年5月至2018年1月中国科学技术大学附属第一医院西区（安徽省肿瘤医院）收治的30例初治DLBCL患者,采用R+DA-EPOCH方案治疗,评价临床疗效与安全性。结果 30例患者中,完全缓解（CR）14例（46.67%）,部分缓解（PR）7例（23.33%）。双重表达淋巴瘤患者治疗有效率为92.31%,非双重表达淋巴瘤患者治疗有效率为52.94%,差异具有统计学意义（P<0.05）。24个月的无进展生存期（PFS）率为86.54%,至随访终点的PFS率为78.67%。结论 R+DA-EPOCH方案对于DLBCL的有效率较高,尤其可克服双重表达对疾病预后的影响,不良反应可耐受,安全性高,值得临床推广应用。     

Monoclonal antibody therapy for B-cell lymphoma: clinical trials of an anti-CD20 monoclonal antibody for B-cell lymphoma in Japan

Twelve patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (B-NHL) were enrolled in a phase I study of rituximab; 4 received rituximab 250 mg/m2 and 8 received rituximab 375 mg/m2 once weekly for 4 weeks. Grade 1 or 2 infusion-related toxicity was observed. Of the 11 eligible patients, 2 achieved complete responses and 5 achieved partial responses. The elimination half-life (T1/2) of rituximab was 445 +/- 361 hours, and serum rituximab levels were detectable at 3 months. Thereafter, 90 relapse patients with indolent B-NHL or mantle cell lymphoma (MCL) were enrolled in a phase II study and treated with rituximab at 375 mg/m2 per infusion in 4 weekly infusions. Sixteen patients were ineligible in protocol compatible analyses. The overall response rates (ORR) in indolent B-NHL and MCL were 61% (37 of 61 patients) and 46% (6 of 13 patients), respectively. Factors affecting response and progression-free survival (PFS) were analyzed for 77 patients whose histopathology was centrally confirmed as indolent B-NHL or MCL. The ORR in patients receiving 1 prior chemotherapy regimen was higher than the ORR in those receiving > or = 2 regimens (P < .05). The median PFS was shorter in MCL patients, in those with extranodal disease, and in those receiving > or = 2 prior chemotherapy regimens (P < .01). The PFS of patients with higher serum rituximab levels (> or = 70 microg/mL) immediately before the third infusion was longer than that of other patients (P < .01). Several pretreatment factors and serum rituximab levels are useful for predicting the efficacy of rituximab monotherapy. Rituximab re-treatment was well tolerated in 13 patients with no grade 3 or 4 nonhematological toxicities. A partial response was observed in 5 patients (38%), and the median PFS after re-treatment was 5.1 months. In conclusion, rituximab is a highly effective agent in relapsed indolent and aggressive B-NHL and MCL and has acceptable toxicities.     

Durable remission induced by rituximab-containing chemotherapy in a patient with primary refractory Burkitt's lymphoma

We describe a 65-year-old man diagnosed with Burkitt's lymphoma arising from the intestine. The tumor cells had a mature B-cell immunophenotype and rearrangement of the c-myc gene. The patient was treated with intensive multiagent chemotherapy. After four courses of chemotherapy, an ileus developed due to a residual abdominal disease. We administered rituximab in combination with the same chemotherapy regimen. A dramatic clinical improvement was observed and abnormal uptake by 18F-fluorodeoxyglucose positron emission tomography disappeared. The patient experienced complete remission for 1 year. This encouraging result indicates that rituximab might be an important treatment choice in management of Burkitt's lymphoma.     

利妥昔单抗在成年人原发性免疫性血小板减少症中的应用进展

原发性免疫性血小板减少症(ITP)是临床上常见的出血性疾病,以抗体介导的血小板破坏及血小板生成不良为特征.原发性ITP的初始治疗方案包括:糖皮质激素及静脉输注丙种球蛋白,而脾切除术、利妥昔单抗、血小板生成素(TPO)受体激动剂等常被用于治疗难治性及慢性原发性ITP患者.笔者拟就利妥昔单抗在成年人原发性ITP中的临床应用及进展进行综述.