Progressive non-infectious anterior vertebral fusion

Four cases of progressive non-infectious anterior vertebral fusion are described. Three cases remain relatively asymptomatic, but one has developed spinal cord compression secondary to an acute angled kyphosis. The clinical, radiological, and pathological features are reviewed and some comparisons with the spinal changes in thalidomide embryopathy are made.     

沙利度胺联合三氧化二砷对急性非淋巴细胞白血病细胞血管内皮生长因子表达的影响

目的 研究沙利度胺和三氧化二砷(As2O3)对急性非淋巴细胞白血病(ANLL)细胞分泌血管内皮生长因子(VEGF)的影响,并研究两者是否有协同作用.方法 收集23例ANLL患者的骨髓液,用Ficoll淋巴细胞分离液分离单个核细胞(MNC),于37℃、5%二氧化碳CO2饱和湿度条件下于RPMI1640培养液中传代培养.取对数生长期细胞以2×106/mL的细胞浓度加入24孔培养板上,沙利度胺以75、150和300μg/mL的浓度加入培养体系中,As2O3以12.5,25和50μmoL/L的浓度加入培养体系中,并将300μg/mL的沙利度胺和50μmol/L的As2O3联合加入培养体系中,同时设空白对照.上述各组分别培养48、72、96和120 h.用ELISA法检测上清液VEGF浓度.结果 沙利度胺和As2O3均可抑制ANLL细胞分泌VEGF,其抑制程度具有剂量-时间依赖性.两药联用的抑制作用更加明显.结论 白血病细胞能自分泌VEGF;沙利度胺和As2O3均能抑制ANLL细胞分泌VEGF;两者联合应用起协同作用.     

反应停治疗恶性浆细胞疾病时的罕见不良反应

目的　进一步认识反应停在治疗恶性浆细胞疾病时可能出现的不良反应。方法　总结应用反应停治疗恶性浆细胞疾病时见到的 4例罕见不良反应的患者 ,并进行相关文献复习。结果　 4例患者出现了几种治疗相关的罕见不良反应 ,包括骨髓抑制、牛皮癣样皮疹、多饮、夜尿增多及高热 ,在停用反应停治疗后其症状逐渐消失。结论　应用反应停治疗恶性血液病的过程中 ,可出现一些少见的不良反应 ,其症状复杂多变 ,临床医生应提高对其警惕性 ,以免误诊。     

Phase II study of topotecan and thalidomide in patients with high-risk myelodysplastic syndromes

This phase II trial investigated the safety and preliminary efficacy of a topotecan/thalidomide combination therapy in patients with myelodysplastic syndrome who had refractory anemia with excess blasts (RAEB), RAEB with transformation, or chronic myelomonocytic anemia. Patients received three 21-day cycles of topotecan 1.25 mg/m² on days 1-5, which was repeated for two additional cycles in patients whose bone marrow blast percentages did not decrease. Oral thalidomide was then started at 100 mg/day (with the dose escalated up to 300 mg/day if well tolerated) for up to 1 year. Patients were monitored throughout the trial for hematologic and clinical adverse events, and efficacy was assessed using International Working Group (IWG) criteria. Forty-five patients, mostly elderly (median age 68 years; range 52-79 years), were enrolled. Therapy was generally well tolerated compared to high-dose chemotherapy. Three patients died from disease progression/infections during topotecan therapy, and four patients discontinued topotecan because of high-grade neutropenia (two patients), syncope (one patient), or hip surgery (one patient). Of 24 patients who received thalidomide, three discontinued because of treatment-related toxicity. Thirty-eight patients were evaluable for response: nine (24%) had hematologic improvement and 13 (34%) had stable disease. Responses occurred in patients with all disease subtypes. Six patients achieved transfusion independence, and one patient had a trilineage response. Approximately one-third of the patients had decreases in bone marrow blasts of ≥50%. Therefore, a topotecan and thalidomide combination therapy is promising, although further studies are needed to determine the optimum doses and schedule.     

Deep vein thrombosis in patients with multiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation

A group of 256 newly diagnosed myeloma patients were enrolled in a phase III study that included 4 monthly cycles of induction chemotherapy and tandem transplant. All patients were randomized to either receive or not receive thalidomide. A total of 221 patients (86%) received no prophylactic anticoagulation (cohort I); 35 patients received low dose coumadin (cohort II). The incidence of deep vein thrombosis (DVT) was significantly higher in the thalidomide arm hazard ratio: 4.5; P < 0.0001). As low dose coumadin (1 mg/d) failed to decrease thrombotic complications in 35 patients (cohort II), low molecular weight heparin (LMWH, enoxaparin 40 mg s.c. q.d.) was instituted as DVT prophylaxis in the thalidomide-treated patients (n = 68) of the subsequent cohort (n = 130, cohort III). This intervention eliminated the difference in DVT incidence between the two arms (thalidomide and no thalidomide). Within cohorts I and II, 36 patients, in whom thalidomide was discontinued after experiencing a thrombotic episode during chemotherapy, subsequently resumed the drug on full anticoagulation; with a median follow-up of 22 months, DVT recurred in four patients (11%). After completing induction and tandem transplantation, 55 patients were re-exposed to thalidomide and chemotherapy during consolidation treatment. Thrombotic complications were observed in 4%. Our experience, although not based on a randomized study, suggests that the excess frequency of thrombosis in patients treated with chemotherapy and thalidomide can be safely reduced by the prophylactic use of LMWH. The rate of DVT recurrence observed in our study upon thalidomide resumption was sufficiently low to allow its continuation in patients who may benefit from this therapeutic intervention.     

门静脉高压大鼠腹膜血管内皮生长因子的表达及意义

目的探讨门静脉高压大鼠腹膜血管内皮生长因子(VEGF)的表达及意义。方法雄性SD大鼠随机分为3组:门静脉结扎(PVL)组32只,假手术(SO)组16只,门静脉结扎联合沙利度安治疗(PVL-T)组8只。为诱导腹水形成,于手术后第1,3,5,7天分批给予每只大鼠腹腔注射33.33%葡萄糖溶液1mL,30min后收集腹水标本并测总量,同时采用ELISA测定腹水中VEGF含量;留取腹膜组织做VEGF免疫组化染色和实时RT-PCR。结果术后第1、3天PVL组大鼠腹水总量和VEGF含量显著大于SO组(P<0.05),术后第5、7天大鼠腹水总量和VEGF含量在PVL组和SO组之间无显著性差异(P>0.05),术后第3天PVL-T组腹水总量显著低于PVL组(3.4±0.27mLvs4.92±1.53mL,P<0.05)。免疫组化结果显示PVL组VEGF呈强阳性表达,而SO组VEGF则呈弱阳性表达,且表达部位多在腹膜间皮细胞、巨噬细胞胞浆;实时RT-PCR结果表明PVL组腹膜VEGFmRNA表达显著高于SO组(P<0.05)。结论门静脉高压可增加由于渗透性改变所致大鼠腹水形成,腹膜VEGF高表达可能与大鼠腹水形成有关,抑制VEGF活性可能是治疗门静脉高压所致腹水的一种新的治疗策略。     

Bortezomib and thalidomide, a steroid free regimen in newly diagnosed patients with multiple myeloma

Despite their efficacy in myeloma, corticosteroids have acute and chronic toxicities. Newer agents with significant anti-myeloma activity permit the development of steroid-free regimens. We designed a Phase II clinical trial to study the toxicity and efficacy of a steroid-free combination of bortezomib and thalidomide as a first-line treatment in patients with symptomatic myeloma. Patients received bortezomib 1·3 mg/m(2) on days 1, 4, 8 and 11 every 21 d and thalidomide 150 mg/d for a maximum of eight cycles. Amongst 27 evaluable patients, the overall response was 81·5% with 25·8% near complete response or greater. The response rate was comparable to most other two drug combinations for upfront therapy but lower than that obtained with the use of three drugs. The most common grade 3 toxicities were peripheral neuropathy (22%), pneumonia (15%), fatigue (7%) and anaemia (7%). Peripheral neuropathy completely resolved in 80% of the patients upon completion of therapy, but not in the remaining 20% of patients. No venous thromboembolic events were observed even in the absence of prophylactic anticoagulation. The median progression-free survival was 16·8 months (95% confidence interval 8·7-21·6 months). Median overall survival has not yet been reached at a median follow up of 39 months. The 3-year overall survival was 74%. This study demonstrates: (i) the efficacy of a steroid-free regimen; (ii) mostly reversible treatment-related peripheral neuropathy; and (iii) the absence of venous thrombotic events.