利妥昔单抗联合化疗治疗弥漫大B细胞性淋巴瘤的疗效观察

目的观察利妥昔单抗联合CHOP（R—CHOP）方案治疗弥漫大B细胞性淋巴瘤的疗效和不良反应。方法弥漫大B细胞性淋巴瘤患者18例应用R—CHOP方案治疗,即利妥昔单抗、环磷酰胺、多柔比星或吡柔比星、长春新碱、泼尼松方案,每3周为1个疗程,均使用6个疗程,观察患者疗效和不良反应。结果18例患者完全缓解10例,部分缓解5例,总缓解率为83．6％。其不良反应主要是骨髓抑制,患者可耐受,不影响治疗。结论R-CHOP方案治疗弥漫大B细胞性淋巴瘤疗效显著,而且全身不良反应较轻。     

利妥昔单抗治疗老年B细胞非霍奇金淋巴瘤11例临床观察

目的观察利妥昔单抗联合化疗对老年人C020阳性B细胞非霍奇金淋巴瘤的临床疗效和不良反应。方法11例经病理及免疫组化证实的CD20阳性的B细胞非霍奇金淋巴瘤患者,每疗程化疗前即第1天给予利妥昔单抗375mg／m^2,第2天开始化疗。采用CHOP方案化疗．每21～28天重复疗程,至少4个疗程。结果总有效率为8／11,完全缓解4／11,部分缓解4／11,稳定2／11,进展1／11;主要不良反应是胃肠道反应、骨髓抑制、脱发等,少数病人出现畏寒、发热、皮肤潮红、血压升高、胸闷等利妥昔单抗输注相关反应,1例患者继发出现口唇疱疹。结论利妥昔单抗联合化疗治疗老年B细胞性淋巴瘤具有良好的临床疗效,其不良反应可为老年患者接受,利妥昔单抗联合CHOP方案适于老年淋巴瘤患者的治疗。     

非骨髓清除性HLA半相合异基因外周血干细胞移植治疗难治性恶性血液病疗效观察

近期 ,我们采用HLA半相合非骨髓清除性HLA半相合异基因外周血干细胞移植 (NSCT)治疗难治性恶性血液病患者 2例 ,取得了较好效果 ,现报告如下。1 　 资料与方法1 .1 　 病例报告例 1　男 ,2 3岁。 1 997年 5月入我院经B超及淋巴结活检等确诊为霍奇金淋巴瘤 ,以淋巴细胞为主 ,ⅢA。经 5个疗程化疗达完全缓解 (CR) ,又给予 2个疗程巩固后于 1 998年 3月行自体外周血干细胞移植 (APBSCT) ,移植后持续CR 2 4个月。 2 0 0 0年 3月左颈部再次出现淋巴结肿大 ,淋巴结活检示APBSCT后复发 ,联合化疗中于同年 1 0月出现腰骶部疼痛 ,B超示脾…     

利妥昔单抗治疗异基因造血干细胞移植后EB病毒病的疗效和安全性

 目的 了解利妥昔单抗治疗异基因造血干细胞移植（allo-HSCT）后EB病毒（EBV）病的疗效和安全性。方法 回顾性分析2006年6月—2012年3月在北京大学人民医院诊断为allo-HSCT后EBV病并应用利妥昔单抗治疗的26例患者,其中临床诊断EBV病15例,活检确诊（移植后淋巴组织增殖性疾病,PTLD）11例。利妥昔单抗静脉输注375 mg/m²,每周1次。采用非霍奇金淋巴瘤（NHL）的疗效标准判定疗效,采用通用的毒性分级标准判定输注过程中的不良反应。结果共应用利妥昔单抗78例次,中位3（1~6）例次。利妥昔单抗输注过程中无严重不良反应发生。治疗后1、2、3、4、8周的累积完全缓解（CR）率分别为（11.5±6.3）%、（42.2±10.2）%、（64.4±10.0）%、（74.6±9.4）%、（87.3±7.9）%。总有效率84.6%,CR率73.1%;单个器官受累患者的CR率高于多器官受累患者（10/10比9/16,P=0.023）,临床诊断的EBV病患者CR率高于PTLD患者(13/15比6/11,P=0.095）,但差异无统计学意义。自首剂利妥昔单抗应用后的1年和2年总生存（OS）率分别为（55.7±10.2）%和（39.6±12.4）%。单器官受累患者的存活率高于多器官受累患者（8/10比5/16,P=0.041）,临床诊断的患者存活多于PTLD患者(11/15比2/11,P=0.015）。结论 利妥昔单抗治疗EBV病安全有效,建议根据临床诊断在单器官受累时即开始治疗,同时争取尽早获取病理结果。利妥昔单抗的治疗方案需要前瞻性研究提供循证医学的证据来进一步规范。     

利妥昔单抗介导的肺损伤的临床特点、处理经验及危险因素

目的:总结利妥昔单抗介导肺损伤的临床特点及处理经验,探讨其可能的危险因素。方法:回顾性分析163例应用利妥昔单抗治疗的患者的临床资料。结果:利妥昔单抗介导的肺损伤发生率为10.4%,年龄是肺损伤发生的高危因素;肺损伤多发生于应用利妥昔单抗3个疗程后,临床常表现为发热、呼吸困难、低氧血症,影像学常表现为间质性肺病,大部分患者对激素治疗有效。结论:利妥昔单抗介导的肺损伤是利妥昔单抗的常见不良反应,及时诊断治疗非常关键。     

利妥昔单抗治疗系统性硬化病八例

目的:观察利妥昔单抗治疗系统性硬化病（SSc）的临床疗效及不良反应。方法:2016年11月至2020年5月就诊于上海瑞金医院风湿科8例接受利妥昔单抗治疗的SSc患者,按在0、2、4、24、48周予以利妥昔单抗治疗的方案给药,分别在治疗前、治疗4、24、48周评估患者的临床症状和实验室指标,采用SPSS 23.0软件进行...     

利妥昔单抗治疗23例狼疮肾炎的疗效与安全性

分析利妥昔单抗治疗23例狼疮肾炎的疗效与安全性, 探索半剂量利妥昔单抗治疗狼疮肾炎的前景。选2013年5月至2021年12月在解放军总医院第一医学中心风湿免疫科住院的23例狼疮肾炎患者, 18例患者于第1天和第14天给予利妥昔单抗375 mg/m2, 5例患者于第1天和第14天给予利妥昔单抗500 mg, 6个月后依病情需要按需使用。第1天和第14天同时给予80～120 mg甲泼尼龙, 后以1 mg/kg甲泼尼龙维持4周, 依病情酌情减量至维持量或停用。记录利妥昔单抗治疗后B淋巴细胞水平、肾功能、24 h尿蛋白定量、系统性红斑狼疮疾病活动指数2000评分(SLEDAI-2K)。分析疗效及不良反应。结果显示, 基线期11例患者存在肾功能不全, 利妥昔单抗诱导治疗后12个月9例患者肌酐水平恢复正常[(66.3±10.1) μmol/L 比 (162.7±58.6) μmol/L]; 12例基线期肾功能正常患者在治疗过程中未出现肾功能恶化。利妥昔单抗诱导治疗12个月后20例患者24 h尿蛋白定量显著降低[4.00(2.00, 6.80)g 比 0.10(0.08, 0.40) g]。利...     

利妥昔单抗联合甲氨蝶呤治疗重度类风湿关节炎的随机双盲安慰剂对照的临床研究

目的 观察利妥昔单抗联用甲氨蝶呤(MTX)治疗重度活动性类风湿关节炎(RA)72周后的疗效和安全性.方法 将患者按2:1:1的比例随机分为500 mg利妥者单抗治疗组、1000 mg利妥昔单抗治疗组及安慰剂组,所有患者同时服用MTX 7.5～20 mg/周,每24周为1个疗程,每疗程于第1日和第15 日输注利妥昔单抗500 mg或1000mg或安慰剂.主要疗效指标为达到ACR20的患者比例,次要疗效指标为达到ACR50、ACR70的比例,及DAS28的改善情况.结果 满足方差齐性,则采用单因素方差分析或t检验方法,如不满足方差齐性,则采用秩转换检验方法.结果 共纳入22例DAS28＞5.1的重度RA患者(女性占93%,平均年龄50岁,MTX平均服用剂量17.6 mg/周),有2例患者因疗效不佳退出,其余患者均完成了 4个疗程的利妥昔单抗治疗,症状明显缓解,在72周结束实验时,500 mg利妥昔单抗组达到ACR20的比例为80%,而1000 mg组达到ACR20的比例为60%,安慰剂+MTX组达到ACR20的比例为57%,同时各治疗组患者红细胞沉降率、DAS28均较基线显著下降.最常见的不良反应为上乎吸道感染,其次是淋巴细胞下降及肝功能异常.结论 利妥昔单抗对RA具有显著的疗效和良好的安全性.     

利妥昔单抗对弥漫大B细胞淋巴瘤患者外周血Th17细胞的作用

目的:研究弥漫大B细胞淋巴瘤(DLBCL)患者接受利妥昔单抗治疗后,外周血Th17细胞比例的变化及其临床意义.方法:分别应用ELISA法和流式细胞术检测DLBCL患者治疗前、接受2个疗程标准RCHOP或CHOP方案诱导缓解治疗后、CHOP诱导治疗未达完全缓解再接受2个疗程RCHOP治疗后达完全缓解者的外周血中IL-17水平以及Th17阳性细胞比例,并与正常对照组比较.结果:DLBCL初治前(50例)外周血Th17细胞比例和IL-17水平较正常对照组(25例)明显升高(均P＜0.05),经RCHOP方案治疗达到完全缓解组(11例)Th17细胞比例、IL-17水平较初治前和较CHOP方案治疗后完全缓解组明显下调(均P＜0.05);CHOP治疗后完全缓解组(14例)Th17细胞比例、IL-17水平,与初治前比较无明显差异,其中8例未达完全缓解者,再接受2个疗程RCHOP达完全缓解,其Th17细胞比例、IL-17水平明显下调(均P＜0.05).结论:利妥昔单抗有下调DLBCL患者外周血Th17细胞比例及IL-17水平的作用,且与疗效有关系.     

利妥昔单抗联合CHOP方案治疗B细胞非霍奇金淋巴瘤疗效观察

对27例CD 20的B细胞非霍奇金淋巴瘤患者采用利妥昔单抗联合CHOP方案治疗4个疗程.治疗后完全缓解16例,部分缓解8例,总有效率87%.所有患者均未见严重的不良反应.认为利妥昔单抗联合CHOP方案治疗B细胞非霍奇金淋巴瘤疗效较好.     

Kidney-limited intravascular large B cell lymphoma: a distinct variant of IVLBCL?

Intravascular large B cell lymphoma (IVLBCL) is a rare type of non-Hodgkin lymphoma characterized by a disseminated intravascular proliferation of tumor cells in the lumina of small vessels. Although the kidney is one of the target organs of IVLBCL, it is extremely rare that lymphoma cells are localized only in the kidney. We report here a Japanese patient with kidney-limited IVLBCL. The patient presented with mild proteinuria and a good performance status without B symptoms at presentation. A renal biopsy showed large B cell neoplastic lymphocytes in the glomerular capillary lumina. Extensive systemic examinations showed no other organ involvement. The patient responded well to rituximab and anthracycline-based chemotherapy. A follow-up renal biopsy showed the disappearance of intraglomerular lymphoma cells with restoration of glomerular architecture. Within 20 months past the discontinuation of chemotherapy, no evidence of recurrence was observed. Although IVLBCL is commonly a fatal disease, favorable clinical courses were reported in some cases of IVLBCL, such as the cutaneous variant. To our knowledge, there are 8 reported cases of kidney-limited IVLBCL in the English literature. All 4 patients treated with intensive chemotherapy responded well to the treatment as our patient. We suggest that kidney-limited IVLBCL might be a distinct variant of IVLBCL.     

Development of Intravascular Large B-cell Lymphoma during Methotrexate Treatment for Rheumatoid Arthritis

A 56-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for six years visited our hospital with dyspnea and dizziness. Abdominal ultrasonography revealed mild splenomegaly. Laboratory examinations showed a marked elevation in soluble interleukin-2 receptor and lactate dehydrogenase levels. These abnormalities revealed a spontaneous regression after MTX discontinuation, however, they worsened again four months later. Skin biopsies revealed a diagnosis of intravascular large B-cell lymphoma (IVLBCL), and we diagnosed MTX-associated IVLBCL (MTX-IVLBCL) based on its characteristic course. Despite the recurrence of IVLBCL, it showed a good response to chemotherapy. MTX-IVLBCL should therefore be treated with consideration since it has different characteristics from that of de novo IVLBCL.     

Occult Diffuse Neoplasm in the Lungs: Intravascular Large B-Cell Lymphoma

BackgroundIntrathoracic involvement with lymphomas is common and manifests lymphadenopathy as well as a wide spectrum of imaging abnormalities in the lungs. Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal subtype of large B-cell lymphoma that typically involves small blood vessels and is difficult to detect.MethodsUsing a computer-assisted search, we identified patients with histopathologically proven IVLBCL in the lungs at Mayo Clinic from 2001 through 2018. Medical records, imaging studies, and pathologic specimens were reviewed.ResultsA total of 5 patients were diagnosed with a median age at diagnosis of 68 years (range, 44-73); 4 patients were male. The diagnosis of IVLBCL was achieved by surgical lung biopsy in 3 and at autopsy in 2. At presentation, all 5 patients had dyspnea and systemic symptoms including fever, fatigue, night sweats, and/or weight loss. Chest radiography and computed tomography (CT) failed to demonstrate the diffuse infiltrative process; positron emission tomography (PET) scan performed in 2 patients did not show fluorodeoxyglucose (FDG) uptake in the lungs. Pulmonary function tests obtained in 3 patients showed reduced diffusing capacity in all; transthoracic echocardiography yielded evidence of pulmonary hypertension in 2 of 4 patients. All 3 patients diagnosed antemortem underwent chemotherapy with 1 patient remaining alive at 4 years after diagnosis.ConclusionsIVLBCL is difficult to diagnose given variable and nonspecific clinical presentations. Microvascular disease processes such as IVLBCL should be kept in mind in cases of undiagnosed progressive dyspnea accompanied by systemic symptoms even when imaging studies are unrevealing.     

Successful treatment of intravascular large B-cell lymphoma diagnosed by bone marrow biopsy and FDG-PET scan

Early diagnosis of intravascular large B-cell lymphoma (IVLBCL) is difficult, but is critical for longer survival for the patients. We report a case of IVLBCL that was diagnosed with the help of FDG-PET. A 76-year-old woman was referred to us for the evaluation of her elevated serum LDH. She presented with general malaise and high fever. There were no skin lesions or neurological involvement. FDG-PET imaging showed increased uptake of FDG in the vertebra, bilateral femurs, sternum, and iliac bones. A diagnosis of IVLBCL was made by bone marrow biopsy. She was successfully treated with rituximab and modified CHOP therapy.     

Sustained complete remission of intravascular large B-cell lymphoma with recurrent CNS involvement by autologous peripheral blood stem cell transplantation preconditioned with TBC regimen

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal large B-cell lymphoma characterized by the growth of lymphoma cells only within the lumina of small vessels in various organs. IVLBCL is an intractable hematological disease, in particular, the high incidence of central nervous system (CNS) involvement is one of the causes of the poor prognosis of IVLBCL. Autologous stem cell transplantation (ASCT) is an effective therapeutic option for refractory or high-risk aggressive lymphoma. However, it is unknown whether ASCT is an effective treatment for CNS involvement of aggressive lymphoma including IVLBCL. We show a case of a 39-year-old woman with recurrent CNS involvement of IVLBCL receiving autologous peripheral blood stem cell transplantation (auto-PBSCT) preconditioned with high-dose thiotepa, busulfan, cyclophosphamide (TBC regimen). Culture-negative febrile neutropenia developed requiring antimicrobial therapy, but nonhematological adverse effects including stomatitis and neurotoxicity, with grade ≥ 3, were not observed. The patient achieved and has maintained complete remission (CR) for 24 months after TBC/auto-PBSCT and has survived for around 30 months from the diagnosis of the CNS recurrence. The clinical course of this case suggests that auto-PBSCT preconditioned with TBC could be one of the therapeutic options for the treatment of CNS involvement of IVLBCL.     

Intravascular large B-cell lymphoma presenting as rapidly progressive dementia and stroke: A case report

Rationale:Intravascular large B-cell lymphoma (IVLBCL) is a rare form of large B-cell non-Hodgkin lymphoma. The diagnosis is challenging and frequently made at biopsy. Here we reported a case of IVLBCL limited to the central nervous system (CNS) presenting with progressive dementia and acute stroke, who was diagnosed by brain biopsy.Patient concerns:A 47-year-old woman was transferred to our hospital with a 6-month history of rapidly progressive dementia, and left limb weakness and numbness for 3 days. She was successively misdiagnosed with inflammatory demyelinating disease and stroke. Her condition deteriorated with elevated lactate dehydrogenase and multiple hyperintense lesions on the brain.Diagnosis:She was diagnosed with IVLBCL limited to the CNS by brain biopsy.Interventions:Bone marrow puncture and incisional random skin biopsy were not found neoplastic cells. Computed tomography scans were normal with no evidence of disease outside the CNS.Outcomes:The patient died due to rapid clinical aggravation.Lessons:IVLBCL limited to the CNS is an aggressive disease with high mortality. Making a timely and correct diagnosis is crucial for early appropriate treatment in IVLBCL patients.     

血管内大B细胞淋巴瘤4例临床报告

目的:探讨血管内大B细胞淋巴瘤(IVLBCL)患者的临床特点及治疗方法。方法:回顾性分析华中科技大学同济医学院附属同济医院收治确诊的4例IVLBCL患者的临床特征、影像学资料、组织活检及免疫组织化学染色、并发症及治疗和预后。结果:4例病例典型临床表现包括不明原因的持续高热,常规抗生素、抗病毒、抗真菌治疗无效,有不同程度的贫血、肝功能不良、低蛋白血症,血清铁蛋白、乳酸脱氢酶(LDH)显著升高。4例免疫表型均表达CD20、CD79a、CD5、Bcl-2、PAX-5、MUM-1、ki67,血管内CD34阳性。病例2、4并发嗜血细胞综合征,称为血管内淋巴瘤病亚洲变异型(AIVL)。IVLBCL目前首选化疗方案为R-CHOP,除病例3外均接受了此方案化疗。病例4随后进行了自体造血干细胞移植+Car-T治疗,目前已完全缓解生存14个月,余3例分别在确诊后18、15、2个月死亡。结论:对于不明原因持续发热的患者,应详细体检,尽早行正电子发射型计算机断层显像(PET-CT)检查,对代谢异常增高的组织行病理学检查,并进行免疫组化染色及流式免疫分型,以便早期诊断或排除IVLBCL。自体造血干细胞移植+Car-T治疗有一定疗效。     

Long-term remission of blastic natural killer-cell lymphoma after autologous peripheral blood stem-cell transplantation

We report here a case of blastic natural killer (NK)-cell lymphoma treated successfully with autologous peripheral blood stem-cell transplantation (APBSCT). A 57-year-old man had skin tumors and was diagnosed as having blastic NK-cell lymphoma by tumor biopsy. Skin, lymph nodes, left tonsil, and bone marrow were involved at presentation. Chemotherapy led to complete remission (CR). To sustain CR, the patient underwent high-dose chemotherapy in combination with 12 Gy of total-body irradiation (TBI) followed by autologous peripheral blood stem-cell rescue. He showed rapid recovery of hematopoiesis and could tolerate regimen-related toxicity after APBSCT. He has maintained long-term remission for 20 months after APBSCT. From this case, we concluded that APBSCT with preconditioning by TBI-containing regimens might be a cure-attaining treatment for disseminated blastic NK-cell lymphoma and should be considered as a choice of treatment in cases where no suitable donors for allogeneic transplantation are available.     

Lymphome à grandes cellules B intravasculaire : trois cas et mise au point

Purpose

Intravascular large B cell lymphoma (IVLBCL) is a rare and aggressive variant of non-Hodgkin's lymphoma, characterized by multifocal proliferation of lymphoma cells exclusively within small and medium blood vessels. IVLBCL can be systemic and quite polymorphic, which often makes it difficult to diagnose, thus delaying appropriate treatment.

Patients and methods

We report three patients of atypical IVLBCL, through the study of which we overview recent knowledge about IVLBCL.

Results

The first patient initially presented with peripheral thrombocytopenia and splenic destruction of platelets, later completed with an interstitial pulmonary syndrome. The second patient, of African origin, we believe is the first case of a black patient with IVLBCL described in the medical literature. The third belongs to the rare group of occidental patients that present an IVLBCL associated with a hemophagocytic syndrome.

Conclusion

Intravascular large B cell lymphoma is a systemic and polymorphic disease. Awareness of this entitiy should allow rapid and appropriate management.     

Intravascular large B-cell lymphoma diagnosed by FDG-PET/CT and endometrial biopsy

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin's lymphoma characterized by a proliferation of tumor cells within the lumina of small to medium-sized vessels. Because there are few or no concomitant solid lesions, a diagnosis of IVLBCL usually cannot be established by CT or MR imaging. Herein, we describe a case of IVLBCL involving the uterus, in which (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was useful for diagnosis. A 47-year-old woman was referred to our hospital because of fever and anemia. Laboratory examination demonstrated anemia and thrombocytopenia. Bone marrow aspiration and biopsy showed hemophagocytosis without involvement of lymphoma cells. Random skin biopsy did not demonstrate lymphoma involvement. FDG-PET/CT imaging showed FDG accumulation in the uterus. MR imaging demonstrated uterine leiomyoma only. Based on these findings, uterine endometrial biopsy was performed and histological diagnosis of IVLBCL involving the uterus was established. She received 6 courses of R-CHOP therapy and high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. At present, she remains in complete remission after 33 months.