多发性骨髓瘤伴肾功能不全15例临床特征与疗效分析

多发性骨髓瘤是浆细胞的肿瘤,患者有20%～40%合并不同程度的肾功能损害,此类患者预后较差.我们对我院血液科经治的15例伴肾功能不全多发性骨髓瘤患者的临床资料进行回顾性分析.     

多发性骨髓瘤合并肾功能不全38例临床和预后分析

目的研究多发性骨髓瘤合并肾功能不全的临床特点及肾功能可逆性的相关因素和生存相关因素。方法回顾性分析1999-01~2003-12北京协和医院收治的91例初治多发性骨髓瘤及其中38例多发性骨髓瘤合并肾功能不全患者的临床资料。结果91例初治多发性骨髓瘤中有38例(41·8%)合并肾功能不全。合并肾功能不全的患者病程进展更快,贫血更严重,血乳酸脱氢酶(LDH)和β2-微球蛋白(β2-MG)质量浓度更高,以及尿蛋白量更多,同时对化疗的反应更差及生存时间更短。其中34·2%的患者肾功能不全是可逆的,血肌酐和LDH是肾功能可逆的独立预测因素。肾功能可逆患者的生存时间与肾功能正常患者的生存时间比较差异无显著性意义。Cox生存多因素分析发现肾功能可逆性(B=1·294,EXP(B)=3·647,P=0·001)是与生存惟一相关的因素。结论肾功能不全是多发性骨髓瘤常见并发症,相当一部分患者的肾功能可以恢复正常,血肌酐水平和LDH水平是肾功能可逆的重要因素,肾功能可逆性是独立的生存预后因素。     

硼替佐米和沙利度胺为主的化疗方案对伴有肾功能不全的多发性骨髓瘤患者的疗效比较

目的:观察以硼替佐米为主和沙利度胺为主的化疗方案治疗伴有肾功能不全的多发性骨髓瘤(MM)患者的疗效,探讨对伴有肾功能不全的MM治疗的最佳方案.方法:40例伴有肾功能不全的MM患者,其中初治20例,复发(难治)20例.选择20例使用以硼替佐米为主的化疗方案作为试验组,以同期20例接受沙利度胺为基础的联合化疗方案治疗的MM...     

老年多发性骨髓瘤肾损害103例的临床特点

目的 探讨老年多发性骨髓瘤(MM)患者的临床特点及其发生肾功能不全的危险因素.方法 对103例MM患者的临床及实验室资料进行回顾性分析,比较老年MM患者特别是发生了肾功能不全的患者与中年MM患者的临床不同点,并用Logistic回归分析老年MM患者发生肾功能不全的危险因素.结果 老年MM患者的肾功能不全(发生率为55%)及尿检异常(发生率为75%)的发生率高于中年MM患者(P＜0.05).老年MM患者的男女比例为2.2∶1,其中有肾功能不全的MM患者的男女比例为4.5∶1高于肾功能正常患者(P＜0.05).老年MM患者中83.3%的临床分期为Ⅲ期,老年MM有肾功能不全患者中93.9%为Ⅲ期.与肾功能正常患者相比,老年MM有肾功能不全患者的溶骨性骨质破坏更严重,浆细胞比例更高.老年MM有肾功能不全的患者的血尿酸、血钙、血磷以及β2-微球蛋白(β2-MG)水平比中年MM患者高,且老年MM有肾功能不全患者的血红蛋白及血清白蛋白水平更低.Logistic回归分析发现性别、血尿酸、血红蛋白、血钙、血磷、白蛋白、血和尿β2-MG的水平与老年MM患者发生肾功能不全有关.结论 老年MM有肾功能不全患者以男性多见,溶骨性损害更严重,代谢紊乱如高尿酸血症、高钙血症、贫血更明显,同时男性、高尿酸血症、高钙血症、低白蛋白血症、贫血为老年MM患者发生肾功能不全的危险因素.     

多发性骨髓瘤治疗

多发性骨髓瘤（MM）是浆细胞异常增殖的恶性克隆性疾病，其特点为血、尿免疫球蛋白和或其片断合成异常、骨病、肾功能不全、血钙异常、感染及贫血等。此病多见于老年人，平均发病年龄62岁。随着我国人口老龄化，近年来此病临床上也渐见增多，故也是老年较常见的肿瘤。     

老年不典型多发性骨髓瘤1例

1例72岁老年患者因胸痛发作多次就诊于亳州市人民医院心血管内科,病程持续4年余,多次行冠状动脉造影检查,提示存在冠状动脉狭窄,予植入支架,术后规则服用阿司匹林、氯吡格雷等药物,后胸痛再次发作,抗心绞痛效果差。胸部CT检查发现存在肋骨骨质破坏,考虑肿瘤转移,予肋骨穿刺活检发现异常浆细胞,后完善一系列相关检查最终确诊为多发性骨髓瘤。患者有经皮冠状动脉介入治疗术后多次胸痛发作病史,且无贫血、高钙血症、球蛋白增高等多发性骨髓瘤特点,漏诊风险较大。予硼替佐米、沙利度胺及地塞米松组成的VTD方案定期治疗后好转。     

老年肾功能不全的评价及诊治进展

随着年龄的增长、生理性老化及多种疾病的共同作用,肾脏组织结构和功能发生明显变化。资料显示,人体30-40岁后,肾脏的重量开始逐渐减轻,肾小球滤过率（glomerular filtrationrate,GFR）进行性下降,65～70岁以后肾功能下降速度加快,70-80岁肾脏的重量下降约20％～30％。     

肾功能不全老年患者臂踝脉搏波传导速度与肾功能的相关性

目的 探讨臂踝脉搏波传导速度(baPWV)在老年慢性肾功能不全患者中与肾功能相关指标之间的关系.方法 选取2011年7月至2012年9月300例60岁以上患者,行baPWV测定,并调查患者的年龄、吸烟、血压,测定空腹血糖、甘油三酯、低密度脂蛋白、高密度脂蛋白、胆固醇、血尿酸、血尿素氮(BUN)、血肌酐(Ser)、尿微球蛋白(β2-MGT)、尿白蛋白.结果 (1)300例患者中动脉硬化224例(74％),其中肾功能不全患者中动脉硬化216例(86％).(2) baPWV升高组与正常组年龄、吸烟、高血压史、空腹血糖、血尿酸有显著性差异(P＜0.05),与其他指标没有明显差异.(3) baPWV升高组与baPWV正常组相比,高血压、糖尿病、COPD发病率高(P＜0.05);两组间冠心病、高脂血症的发病率无显著性差异.(4)老年肾功能不全患者baPWV与肾BUN、Scr、β2-MGT、低蛋白血症呈正相关性,而与Ccr呈负相关.(5)肾功能损伤越严重,baPWV值越高.结论 baPWV可以早期评价老年肾病患者肾功能情况.     

硼替佐米为主的联合方案治疗复发或难治性多发性骨髓瘤

目的 观察硼替佐米为主的联合方案治疗复发、难治性多发性骨髓瘤(MM)的疗效和不良反应,探讨应用硼替佐米治疗的最佳方案、剂量及疗程.方法 复发、难治性MM患者46例,均在3～4周的疗程内,给予硼替佐米1.3 mg/m2,1、4、8、11 d,同时联合地塞米松(D)、D+沙立度胺(T)、环磷酰胺(C)+D、米托蒽醌(M)+D、DC+鬼臼乙叉甙(E)+顺铂(P)和DT-P+阿霉素(A)+CE等化疗方案.采用国际骨髓瘤工作组(IMWG)标准判断疗效,并按美国国立癌症研究院不良事件通用命名标准(NCI CTCAE)(第3版)观察不良反应.以接受沙立度胺为基础的联合方案治疗的49例复发、难治MM作历史对照研究.结果 在可评估的43例患者,中位随访时间10个月,31例获得不同程度的缓解,总有效率为72.1%(对照组为51.0%,P＜0.05).其中完全缓解(CR)5例(11.6%),很好的部分缓解(VGPR)12例(27.9%),部分缓解(PR)14例(32.6%).接受1个疗程和2个疗程的总有效率分别为30.2%、58.1%(P＜0.05).常见的不良反应为血小板减少(62.8%)、乏力(55.8%)、恶心(51.2%)及周围神经病变(30.2%)等,但均能耐受.对照组的不良反应有便秘(69.4%)、乏力(59.2%)和头昏、头晕(46.9%)等.结论 硼替佐米为主的联合方案是一种对复发、难治性MM新的治疗选择,疗效优于沙立度胺为基础的联合方案,且两者毒性谱有所不同.     

硼替佐米联合地塞米松治疗多发性骨髓瘤的临床研究

目的观察硼替佐米联合地塞米松治疗多发性骨髓瘤(MM)的疗效和不良反应。方法2005年6月至2007年7月收集温州医学院附属第一医院14例MM患者,其中男11例,女3例;年龄52~77岁,平均年龄为65.1岁。第1,4,8和11天给予静脉推注硼替佐米1.3mg/m2;第1~4天,8~11天给予地塞米松20~40mg静脉滴注,每例患者接受1~8个疗程的治疗。采用欧洲骨髓移植协作组(EBMT)标准观察疗效,并按美国国立癌症研究所(NCI)(第3版)CTCAE标准判断不良反应。结果中位随访时间为3.5(1.3~10)个月,12例(86%)患者对治疗有效,其中2例完全缓解,6例患者接近完全缓解,3例部分缓解,1例轻微反应;2例进展。14例患者中10例出现不同程度的乏力,7例出现周围神经病变,腓肠肌酸痛2例,4例出现胃肠道症状,5例血小板减少,1例播散型带状疱疹,1例顽固性低钠血症。均经对症治疗基本缓解。结论硼替佐米联合地塞米松是治疗MM的新的有效治疗方法,不良反应稍多,但经对症治疗及调整用药剂量后均能改善。     

Safety and efficacy of bortezomib‐based regimens for multiple myeloma patients with renal impairment: a retrospective study of Italian Myeloma Network GIMEMA

Renal impairment (RI) is a severe complication throughout the course of multiple myeloma (MM). Bortezomib has been shown to be highly active in MM patients with RI. We designed this retrospective analysis to investigate the safety and efficacy of bortezomib‐based therapy in 117 MM patients with RI, 14 cases required dialysis. A total of 603 cycles of bortezomib were administered (median number, five cycles/patient). Ten patients required early discontinuation of bortezomib because of WHO grade IV toxicity. The rate of bortezomib discontinuation in cases with severe, moderate and mild RI was 11%, 5% and 0%, respectively (P = NS). Overall, 91 episodes of WHO grade III/IV toxicity were observed. At least a partial response was documented in 83/113 evaluable patients (73%), including complete response (19%) and near complete response (8%). The overall response rate was similar across RI subgroups. Reversal of RI was documented in 41% of patients after a median of 2.3 months (range 0.4–7.9). In three of 14 patients on dialysis, renal replacement therapy was discontinued after 1, 1 and 4 months. The 2‐yr estimate of response duration and overall survival was 70% and 51%, respectively. In conclusion, bortezomib‐based regimens are safe and effective and should be considered as appropriate treatment options for MM patients with any degree of RI.     

Bortezomib in multiple myeloma

Multiple myeloma (MM) remains an incurable disease, and novel agents are therefore needed to improve outcome. Bortezomib is the first proteasome inhibitor to be approved by the US Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products for the treatment of refractory/relapsed MM. Bortezomib has demonstrated significant anti-myeloma activity as a single agent in refractory/relapsed MM. When used in combination with other agents, responses have suggested the possibility of chemosensitization and synergy. All these facts have been the rationale for the use of bortezomib-based regimens as upfront treatment in young and elderly newly diagnosed MM patients. Furthermore, bortezomib does not appear to have an adverse effect on subsequent stem-cell collection. Bortezomib is well tolerated; most side-effects are only mild to moderate and manageable. Practical management of these side-effects is given so that they can be recognized and minimized by dose modification or concomitant therapy.     

Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma

Adverse prognostic factors in multiple myeloma include advanced age, number of prior therapies, and higher International Staging System (ISS) disease stage. In the international, randomised, phase-3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study, bortezomib demonstrated significantly longer time to progression (TTP), higher response rates and improved survival compared with high-dose dexamethasone in patients with relapsed multiple myeloma following one to three prior therapies. In this APEX subgroup analysis, efficacy of bortezomib and dexamethasone was compared in elderly (age > or =65 years) and high-risk (>1 prior line of therapy; ISS stage II/III; refractory to prior therapy) patients. Bortezomib demonstrated substantial clinical activity in these patients. Response rate (34-40% vs. 13-19%), including complete response rate (5-8% vs. 0-1%), was significantly higher with bortezomib versus dexamethasone in all four subgroups. Similarly, median TTP was significantly longer with bortezomib versus dexamethasone, and 1-year survival probability was significantly higher in all subgroups. As in the total APEX population, rates of grade 3/4 adverse events were higher in bortezomib- versus dexamethasone-treated patients aged > or =65 years and with >1 prior line, while rates of serious adverse events were similar; toxicities generally proved manageable. Bortezomib should be considered an appropriate treatment for elderly and high-risk patients with relapsed multiple myeloma.     

Community experience with bortezomib in patients with multiple myeloma

Community practice experience allows a nonselective care of patient using information derived from a more controlled clinical trial environment. We present our community experience with multiple myeloma patients with advanced age, long disease duration since diagnosis, advanced stage, multiple prior therapies including stem cell transplantation, co-morbidities, and other poor prognostic features, such as low albumin, high B-2 microglobulin, renal failure, and the presence of poor risk chromosomal abnormalities. Our response rates are comparable to those from clinical trials. Bortezomib is well tolerated in this population of multiple myeloma patients with the exception of infection adverse events that are generally mild grade 1-2.     

Bone scan images reveal increased osteoblastic function after bortezomib treatment in patients with multiple myeloma

Osteolytic lesions with activated osteoclast (OC) and suppressed osteoblast (OB) activity are characteristics of myeloma bone lesion. Recently, it has been shown that bortezomib treatment enhances OB function. To evaluate the effect of bortezomib on myeloma bone lesions, we performed bone scans, where increased uptake of the radiopharmaceutical by OBs is associated with re-building activity. Bortezomib treatment markedly enhanced bone metabolic activity and increased alkaline phosphatase levels, and decreased monoclonal protein levels. These findings suggest that bortezomib has potent anti-myeloma activity and bone-protecting effects, with enhanced OB function.     

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.     

High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program

Phase 2 trials have demonstrated that bortezomib ± dexamethasone is safe and effective in relapsed multiple myeloma (MM). In this multicentre, open-label, phase 3b trial, 638 patients with relapsed or refractory MM (median 3 prior therapies) received bortezomib 1·3 mg/m² on days 1, 4, 8, and 11 of a maximum of eight 3-week cycles (median 5 cycles). Dexamethasone 20 mg/d was added the day of and day after each bortezomib dose for progressive disease after ≥2 cycles or for stable disease after ≥4 cycles. Responses were assessed based on M-protein changes. Overall response rate was 67%, including 11% complete (100% M-protein reduction), 22% very good partial (75–99% reduction), 18% partial (50–74% reduction), and 16% minimal response (25–49% reduction). Dexamethasone was added in 208 patients (33%), of whom 70 (34%) showed improved response. Median time to best response of minimal response or better was 84 d. Most common grade 3/4 adverse events were thrombocytopenia (39%), neutropenia (16%), anaemia (12%), diarrhoea (7%), and peripheral neuropathy (6%). Neuropathy (any grade) was seen in 25% of the patients and led to discontinuation in 5%. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM.