硼替佐米和沙利度胺治疗对多发性骨髓瘤患者外周血T细胞亚群及相关细胞因子的影响

目的探讨分析硼替佐米和沙利度胺治疗对多发性骨髓瘤(MM)患者外周血T细胞亚群及相关细胞因子的影响。方法选择2016年3月-2018年3月本院收治的初发MM患者78例,随机分为硼替佐米组40例、沙利度胺组38例,再选择50例健康志愿者作为对照组。硼替佐米组患者给予硼替佐米联合地塞米松治疗,沙利度胺组患者给予沙利度胺、长春新碱、表柔比星联合地塞米松治疗。比较2组治疗疗效,检测2组MM患者治疗前后及对照组外周血Th17、Treg细胞比例以及IL-6、IL-17、TGF-β水平。结果 2组MM患者治疗后Treg显著升高(P 0.05),Th17细胞比例显著降低(P 0.05),且硼替佐米组改善程度更优(P 0.05)。2组MM患者治疗后血清IL-6、IL-17以及TGF-β水平较治疗前显著降低(P 0.05),且治疗后硼替佐米组血清IL-6、IL-17以及TGF-β水平显著低于沙利度胺组(P 0.05)。结论硼替佐米和沙利度胺治疗多发性骨髓瘤均具有一定的疗效,可有效改善机体Treg、Th17细胞比例,降低血清IL-6、IL-17以及TGF-β细胞因子表达,且以硼替佐米联合地塞米松治疗方案效果更佳。     

硼替佐米地塞米松沙利度安联合治疗伴肾功能不全的初治多发性骨髓瘤的疗效观察

目的 用硼替佐米地塞米松沙利度安联合治疗伴肾功能不全的初治多发性骨髓瘤,以探讨治疗多发性骨髓瘤并肾功能不全患者有效安全的方法;方法硼替佐米1.0-1.3mg/m2,静脉注射,d1、d4、d8、d11;地塞米松20-40mg/d,静脉注射,d1-4.沙利度安100mg/d,晚服.28天一疗程.结果 12例患者中获完全缓解5例,部分缓解4例,总有效率85%,患者肾功能得到逆转,不良反应可耐受;结论硼替佐米地塞米松沙利度安联合治疗伴肾功能不全的初治多发性骨髓瘤是安全有效的治疗方法.     

自体周血干细胞移植治疗多发性骨髓瘤研究进展

与传统化疗相比,自体干细胞移植患者完全缓解（CR）、非常好的部分缓解（VGPR）、无进展生存期及总生存期均明显提高,已成为65岁以下初治多发性骨髓瘤患者一线治疗。新药沙利度胺、来那度胺和硼替佐米联合地塞米松用于移植前的诱导化疗、预处理和维持治疗,显示出良好疗效,已逐步取代传统化疗方案,在复发和进展患者中亦显示出明显的疗效。初步研究提示来那度胺和硼替佐米可克服不利遗传学异常影响。     

硼替佐米与雷利度胺联合地塞米松治疗多发性骨髓瘤的疗效及感染分析

目的对比硼替佐米与雷利度胺联合地塞米松治疗对多发性骨髓瘤(MM)的疗效,为MM的临床治疗方案选择提供理论依据。方法选取医院2008年6月-2010年6月收治的190例MM患者,按照随机数字表分为A、B两组,各95例,分别实施硼替佐米联合地塞米松方案与雷利度胺联合地塞米松方案进行治疗,比较两组患者治疗前后血红蛋白、血清肌酐、血清M蛋白及骨髓浆细胞等指标,分析疗效。结果两组治疗后血红蛋白显著上升,血清肌酐、血清M蛋白及骨髓浆细胞均显著下降,且B组改变程度较A组更为显著;A组完全缓解10例,非常好的部分缓解24例,部分缓解25例,总有效率61.1%,B组分别为16、31、28例,总有效率78.9%,B组治疗效果显著优于A组;A组及B组患者不良反应发生率分别为23.2%及7.4%,A组患者出现4例肺部感染,B组出现2例医院感染。结论硼替佐米联合地塞米松方案与雷利度胺联合地塞米松方案均可有效改善MM患者临床症状,使其预后和生活质量得到提高,而雷利度胺联合地塞米松方案具有更好的疗效及减少肺部感染机会,是治疗以中老年患者为主的MM的黄金方案,值得临床广泛推广。     

以硼替佐米为基础的化疗方案对多发性骨髓瘤的疗效及预后

目的观察以硼替佐米为基础的化疗方案治疗多发性骨髓瘤(MM)的疗效及预后效果。方法随机选取本院于2016年10月至2017年10月收治的46例多发性骨髓瘤患者,将其中23例初治疗者纳入A组,其余23例复发、难治者纳入B组。A照组患者采取硼替佐米联合地塞米松化疗方案(PD),B组患者则采取硼替佐米联合吡柔比星及地塞米松化疗方案(PAD)。两组均进行1～6疗程治疗,之后口服沙利度胺维持治疗,观察两组疗效、不良反应及预后情况。结果两组患者均随访4～35个月,平均随访时间为17个月。随访中发现A组总体缓解率为86.96%,高于B组的60.87%,差异有统计学意义(P0.05)。两组MM患者在采取以硼替佐米为基础的化疗方案治疗中,主要毒副反应包括17例胃肠道反应,22例血小板减少,15例白细胞减少,11例周围神经病变,15例感染。A组发生胃肠道反应7例(30.43%),白细胞减少7例(30.43%),周围神经病变5例(21.74%),感染6例(26.09%)。B组发生胃肠道反应10例(43.48%),白细胞减少8例(34.78%),周围神经病变6例(26.09%),感染9例(39.13%)。两组患者不良反应发生例次率比较差异无统计学意义(P0.05),两组均未发生严重反应,患者经对应处理或停药后多数有改善,部分为不可逆改变。结论对初治多发性骨髓瘤患者应用硼替佐米与地塞米松联合化疗方案具有迅速减小肿瘤、整体反应率低、完全缓解率高的优点,但对于复发难治性患者虽然治疗反应率较好,但疗效低于初治者。该治疗方案不良反应例次率较高,但均能够预测和控制,患者整体耐受性较好。     

沙利度胺联合地塞米松治疗多发性骨髓瘤临床观察

目的 观察低剂量(200mg·d-1)沙制度胺联合地塞米松松(TD)治疗初发多发性骨髓瘤(MM)的临床疗效和不良反应.方法 14例初治MM患者,给予沙利度胺100mg/d起,每周增加50mg至200mg·d-1,28d为一疗程,至少3个疗程.同时TD静脉注射10mg·d-1,每月第1～7天,每月重复.结果 14例初发多发性MM中部分缓解7例,平均缓解时间46.3d,4例进步,3例无效,总有效率为78.6％.14例患者不同程度的便秘、嗜睡、皮疹,但不良反应轻微,均可耐受.结论 低剂量沙利度胺联合TD治疗初发MM安全有效,且副作用轻.     

地塞米松联合沙利度胺治疗多发骨髓瘤18例疗效分析

目的 地塞米松联合沙利度胺治疗多发骨髓瘤(MM)的临床疗效及其患者不良反应.方法 MM患者18例,其中包括10例难治复发和8例初发,地塞米松20 mg/d静脉点滴,第1～4天,第15～18天,每28 d为1个周期,治疗4个周期;同时沙利度胺100～200 mg/d口服,每28 d为1个周期,共4个周期.结果 完全缓解9例,部分缓解5例,进步3例,无效1例;不良反应可以耐受,轻度便秘及嗜睡多见,2例肺部感染,1例深静脉血栓.结论 地塞米松联合沙利度胺治疗MM安全、有效,患者耐受性好.     

常规化疗联合硼替佐米、沙利度胺治疗对新发骨髓瘤患者肾功能的影响

目的:分析常规化疗联合硼替佐米、沙利度胺治疗新发骨髓瘤患者的效果,探讨其对肾功能的影响.方法:随机将88例患者分成对照组、观察组,对照组利用常规方法治疗,观察组联合使用常规化疗、硼替佐米及沙利度胺进行治疗,对比两组患者的病情缓解与肾功能改善情况.结果:观察组患者肾功能逆转与肾功能好转均高于对照组,差异对比不存在统计学意义,P>0.05;观察组总有效率、总体有效率明显高于对照组,差异明显,具有统计学意义,P<0.05.结论:联合利用常规化疗、沙利度胺及硼替佐米对新发骨髓瘤患者进行治疗,可以获得较为明显的临床效果,有效逆转患者肾功能,值得在临床治疗中进行进一步推广     

硼替佐米对多发性骨髓瘤患者联合化疗安全性及预后的影响

目的分析硼替佐米对多发性骨髓瘤(MM)患者联合化疗安全性及预后的影响,探讨其临床价值。方法选取宿州市立医院2014年1月～2016年1月收治的86例MM患者,使用随机数表法,纳入观察组和对照组,每组43例。对照组接受长春新碱+阿霉素+地塞米松(VAD±T)联合化疗方案治疗,联合或不联合沙利度胺;观察组在对照组治疗方案的基础上,加用硼替佐米治疗。评价两组患者治疗效果、不良反应及3年总生存期(OS)、无进展生存期(PFS),分析硼替佐米在MM联合化疗中的应用价值。结果疗程结束后,观察组总有效率为53.48%,高于对照组的30.23%,差异有统计学意义(P 0.05)。两组患者化疗期间不良反应发生情况比较,差异无统计学意义(P 0.05)。观察组随访期间失访2例,对照组失访3例,其余患者均获得有效随访,随访时间均≥3年。观察组中位PFS、OS分别为17个月、26个月,高于对照组的12个月、19个月。结论在常规联合化疗方案的基础上加用硼替佐米,能够在保证治疗安全性的前提下改善患者预后质量,延长生存时间,值得广泛应用。     

硼替佐米、地塞米松联合治疗多发性骨髓瘤的临床疗效观察

[目的]探讨硼替佐米、地塞米松联合治疗多发性骨髓瘤的临床疗效及安全性。[方法]选取2008年6月~2009年12月在我科经硼替佐米联合地塞米松(VD)治疗的多发性骨髓瘤(MM)患者16例作为VD组,并选取同期在我科经VAD(长春瑞宾+阿霉素+地塞米松)治疗的25例MM患者作为VAD组,观察两组治疗效果及安全性,并对VD治疗方案在初治和复发患者中疗效、轻链型和非轻链型患者中的疗效进行对比分析。[结果]VD组总有效率为87.50%,明显高于VAD组的48.00%,组间比较差异有统计学意义(P﹤0.05);VD组在初治和复发MM患者中疗效相当,在轻链型患者中CR率高于非轻链型患者;VD组不良反应轻微,均为可逆性。[结论]VD化疗方案治疗MM,具有疗效好、不良反应小等优点,是目前治疗MM的一种较佳化疗方案,值得临床推广应用。     

减低剂量及标准剂量硼替佐米联合疗法对不同类型多发性骨髓瘤的近期疗效对比

目的 探讨减低剂量及标准剂量硼替佐米联合阿霉素、地塞米松治疗不同类型多发性骨髓瘤（MM）的近期疗效及安全性.方法 对52例初诊、复发及难治MM患者给予硼替佐米1.3 mg/m2（标准剂量组,26例）或1.0～1.1 mg/m2（减低剂量组,26例）,第1,4,8,11天快速静脉注射,阿霉素10 mg/m2,第1～4天静脉注射,地塞米松40mg/d,第1～4天静脉滴注,治疗1～6个疗程.比较两组患者的疗效和不良反应.结果 标准剂量组治疗总反应率为80.8％（21/26）,与减低剂量组的88.5％（23/26）比较差异无统计学意义（P=0.739）;两组白细胞、血小板减少发生率比较差异均无统计学意义[23.1％（6/26）比15.4％（4/26）,P=0.281;11.5％（3/26）比7.7％（2/26）,P=0.620];标准剂量组与减低剂量组比较,由硼替佐米诱导的Ⅲ～Ⅳ级周围神经病[15.4％（4/26）比3.8％（1/26）,P=0.038）]、带状疱疹[26.9％（7/26）比7.7％（2/26）,P=0.029]、乏力[38.5％（10/26）比15.4％（4/26）,P=0.045]及腹胀发生率[19.2％（5/26）比3.8％（1/26）,P=0.028]前者均高于后者,差异有统计学意义.结论 减低剂量联合疗法治疗初诊和复发、难治MM患者的疗效反应与标准剂量类似,但患者对减低剂量联合方案具有更好的耐受性.     

诱导期初治多发性骨髓瘤患者医院感染的临床特征

目的探索初诊多发性骨髓瘤(MM)患者诱导治疗期间医院感染发生情况及临床特征。方法收集某医院接受PAD(硼替佐米+阿霉素+地塞米松)与PDD(硼替佐米+脂质体阿霉素+地塞米松)方案治疗的116例初治有症状的MM患者临床资料,统计诱导治疗期间感染率及临床特点。结果 116例MM患者其中69例接受PAD方案治疗,47例接受PDD方案治疗,两组的感染发生率分别为79.7%和89.4%。73例为皮下注射硼替佐米,43例接受静脉注射,皮下注射组感染发生率为78.1%,静脉注射组为93.0%,各组比较差异有统计学意义(P0.05)。诱导期间医院感染发病率为83.6%(97例),其中第一疗程81例出现感染,3例外院治疗具体感染不详,实际感染发病率为71.7%(81/113);第二疗程感染发病率为56.6%(64/113);共98例患者完成三个疗程治疗,感染发病率为43.9%(43/98);共66例患者完成四个疗程治疗,感染发病率为28.8%(19/66)。随着疗程的推进,感染率呈下降趋势。感染的部位从高到低依次是呼吸系统、皮肤及黏膜、口腔及胃肠道、血液、泌尿道。化疗期间是否预防性应用抗真菌药物的两组患者临床诊断构成比较,差异无统计学意义(P=0.063)。结论诱导期间感染发病率极高,主要的感染部位是呼吸系统,临床医生与患者均需加强呼吸系统感染的防治。     

小剂量沙利度胺联合VAD方案治疗多发性骨髓瘤的体会

目的：观察小剂量沙利度胺联合VAD方案（长春新碱、阿霉素、地塞米松）治疗多发性骨髓瘤的疗效和不良反应。方法：对照组20例多发性骨髓瘤采用VAD方案,每28天一个疗程;治疗组22例多发性骨髓瘤患者均采用小剂量沙利度胺（200 mg.d-1）联合VAD方案治疗。3个疗程后行疗效和不良反应评估。结果：治疗组总有效率81.8%,明显优于对照组（60.0%）;治疗组不良反应轻微,主要的不良反应为白细胞减少、胃肠道反应,与对照组相比无差异。结论：小剂量沙利度胺联合VAD方案治疗多发性骨髓瘤疗效高,不良反应轻微,值得临床推广。     

Modern treatment methods for multiple myeloma: guidelines from the Dutch Haemato-Oncology Association (HOVON)

The treatment for multiple myeloma has undergone many changes over the past decade. Intensive therapy with autologous stem-cell support has improved the clinical outcome significantly in younger patients. Reduced intensity conditioning regimens have lowered the high treatment-related mortality of myeloablative allogeneic transplantation. New effective anti-myeloma drugs such as bortezomib and thalidomide analogues have become available. These new developments have made it necessary to formulate recommendations to facilitate decisions concerning the management of myeloma patients. The Myeloma Working Party of the Dutch Haemato-Oncology Association (Stichting Haemato-Oncologie voor Volwassenen Nederland) has developed therapy guidelines based on phase-II and phase-III studies as well as the expertise of the working party. These include upfront induction therapy followed by autologous transplantation for patients aged up to 65 years and oral melphalanprednisone treatment for patients with severe co-morbidities and patients over the age of 65 years. Patients under the age of 66 with an HLA-identical (family) donor are candidates for non-myeloablative stem-cell transplantation following autologous stem-cell transplantation. For second-line treatment, thalidomide, combined with dexamethasone is recommended. Younger patients responding to second-line treatment are candidates for a second autologous transplant. Bortezomib is indicated for those patients refractory to the previous two lines of treatment. All patients should receive long-term bisphosphonates. Erythropoietin may be considered in symptomatic anaemia as well as antibiotic prophylaxis during induction therapy which includes dexamethasone.     

Proteasome inhibition: a new therapeutic approach for the treatment of multiple myeloma

Multiple myeloma is the second most common hematologic malignancy with currently no definitive treatment available. Although, therapy may include allogenic bone marrow transplantation, high-dose ablative chemotherapy followed by bone marrow or peripheral stem cell transplantation, melphalan/corticosteroid therapy, alpha-interferon treatment, and combined cytostatic chemotherapy, currently none of these alternatives offer cure for the disease. Introduction of thalidomide into the therapeutic arsenal provided a breakthrough in the treatment of refractory and/or relapsing disease, however, clinical experience indicated need for alternative treatments for thalidomide resistant disease as well as for intolerant patients. Proteasome inhibitors, hallmarked by bortezomib may represent one of the much needed therapeutic options. The results of the SUMMIT investigation that involved 202 heavily pretreated patients were convincing enough to prompt the FDA to register this drug for the treatment of multiple myeloma. Its European registration is also underway. In this review, the proteasome and its inhibition as a pharmacotherapeutic avenue are introduced. The most important clinical studies employing bortezomib and its combinations are also detailed. It is the hope of the authors that bortezomib and its derivatives will soon belong to the clinical armory against multiple myeloma.     

硼替佐米治疗多发性骨髓瘤致周围神经感觉异常的护理体会

通过对6例多发性骨髓瘤患者在接受硼替佐米联合地塞米松治疗的观察,研究B族维生素的镇痛作用,实施有效的护理措施,对患者进行心理干预,提高生活质量,积极地影响硼替佐米对治疗多发性骨髓瘤的效果。     

多发性骨髓瘤合并股骨颈骨折的治疗

目的 探讨外科手术干预联合药物治疗多发性骨髓瘤合并股骨颈骨折的疗效.方法 多发性骨髓瘤合并股骨颈骨折12例患者,采用骨水泥型长柄股骨头全髋关节置换术,术后所有患者接受唑来膦酸治疗及针对原发病治疗,其中7例行MPT(美法仑、甲泼尼龙、沙利度胺)方案化疗,3例采用硼替佐米联合地塞米松治疗,1例行自体外周血造血干细胞移植.结果 12例患者均能耐受手术,术后疼痛明显减轻.术后6个月Harris评分优2例,良7例,一般3例,优良率为75％(9/12).术后随访8个月至3年,1例13个月后局部复发,1年总生存率100％,2年总生存率83％,3年总生存率67％.结论 多发性骨髓瘤合并股骨颈骨折患者采用骨水泥型长柄股骨头全髋关节置换术可清除局部肿瘤病灶,重建功能,术后恢复快,缓解疼痛,为进一步综合治疗争取机会.术后接受双膦酸盐治疗可促进新骨形成,预防再次骨折发生;外科手术干预局部处理的同时应标本兼治,针对原发病多发性骨髓瘤积极治疗,降低肿瘤细胞负荷,提高患者生活质量,延长生存时间.     

多发性骨髓瘤X线摄影体位的探讨

目的 探讨多发性骨髓瘤平片检查的首选体位.方法 以回顾性研究的方法对101例经骨穿确诊的多发骨髓瘤患者临床资料进行分析,并对颅骨、腰椎、胸部和骨盆四组常用摄影体位片进行比较.结果 在多发性骨髓瘤患者中头颅、腰椎、肋骨和骨盆阳性率分别为86%、28%、20%和19%,以头颅最高;头颅平片能够显示＂纱布眼＂样细微骨质破坏;头颅平片多发＂穿凿样＂,＂油滴样＂骨质破坏具有典型性.结论 头颅平片可作为多发性骨髓瘤溶骨性病变诊断的首选体位.     

Estimating the Costs of Therapy in Patients with Relapsed and/or Refractory Multiple Myeloma: A Model Framework

Background

Multiple myeloma is a progressive cancer for which there is no cure. Despite treatment, almost all patients eventually experience periods of disease relapse and remission. With the increasing use of novel therapies, including bortezomib, lenalidomide, carfilzomib, pomalidomide, and panobinostat, benchmarks for assessing the value of these therapies in treating patients with relapsed or refractory multiple myeloma (RRMM) are needed for physicians and payers alike.

Objectives

To develop a model framework and to calculate an annual estimate of the total costs per patient for the treatment of patients with RRMM using 7 common treatment regimens, including bortezomib plus dexamethasone; panobinostat, bortezomib, and dexamethasone; lenalidomide plus dexamethasone; lenalidomide, bortezomib, and dexamethasone; carfilzomib; carfilzomib, lenalidomide, and dexamethasone; and pomalidomide plus dexamethasone.

Methods

The expenditures for drugs and their administration, for prophylaxis and adverse event monitoring, and for the treatment of grade 3 or 4 adverse events were included in the calculations of the total pharmacy and medical costs. The drug costs were based on published pricing and labeled dosing schedules; the adverse event prophylaxis and monitoring costs were obtained from peer-reviewed publications; and the adverse event incidence rates were obtained from each regimen''s prescribing information and from clinical trials. All the costs were summed over the duration of therapy for which the drugs were administered and were calculated separately for commercial and Medicare plans. The duration of therapy for each regimen was the time for which a patient had to be receiving the regimen to obtain 12 months of progression-free survival based on the duration-of-therapy to progression-free survival ratio observed from published clinical trials and/or the drug''s labeling.

Results

The pharmacy costs were highest for pomalidomide plus dexamethasone, whereas the medical costs were highest for the combination of carfilzomib, lenalidomide, and dexamethasone. The total cost associated with available treatments for RRMM was highest for regimens that included lenalidomide (approximate range, $126,000-$256,000). Only bortezomib plus dexamethasone and the combination of panobinostat, bortezomib, and dexamethasone had total costs that were lower than $125,000 per patient.

Conclusion

This study represents the first model developed to comprehensively estimate the costs of managing RRMM with all currently approved and guideline-recommended regimens in the United States. As such, it provides the framework and basis for further budget impact analyses and for cost-effectiveness comparisons with these regimens.