沙利度胺联合化疗治疗难治性多发性骨髓瘤

目的：观察沙利度胺联合化疗治疗难治性多发性骨髓瘤(MM)的疗效及其副作用。方法：5例患者均给予沙利度胺联合化疗,沙利度胺的剂量为400mg／d～800mg／d,根据血清M蛋白和骨髓瘤细胞的减少判断疗效。结果：总有效率为80%无不能耐受的毒副作用。结论：沙利度胺联合化疗可作为难活性多发性骨髓瘤有效的治疗方法。     

沙利度胺联合干扰素治疗复发难治T细胞淋巴瘤二例并文献复习

目的 探讨沙利度胺联合干扰素治疗复发难治T细胞淋巴瘤(TCL)的效果及患者不良反应.方法 观察使用沙利度胺联合干扰素治疗2例复发难治TCL患者的效果及不良反应,并复习相关文献.结果 2例患者均达部分缓解(PR),无明显不良反应.结论 沙利度胺联合干扰素治疗复发难治TCL有一定的疗效,可作为治疗复发难治TCL的一种新的选择.     

小剂量沙利度胺治疗多发性骨髓瘤的临床观察

 目的 观察小剂量沙利度胺联合地塞米松和化疗治疗多发性骨髓瘤（MM）的疗效和毒副作用。方法 7例MM患者予沙利度胺口服,起始剂量50 mg／d ,至最大剂量50 ~ 300 mg,联合地塞米松或VAD方案化疗。结果 4例患者部分缓解（PR）,2例患者进步,1例患者无效,总有效率达85 %。毒副作用有嗜睡、乏力、便秘、皮疹、手足麻木,毒副反应轻。结论 小剂量沙利度胺联合地塞米松和化疗治疗MM是安全有效的。     

沙利度胺联合地塞米松治疗多发性骨髓瘤的临床疗效

目的观察沙利度胺联合地塞米松治疗多发性骨髓瘤(MM)的临床疗效及毒副反应。方法 50例MM患者随机分为2组,对照组采用VAD方案化疗,观察组采用地塞米松联合沙利度胺方案化疗,对比2组的临床疗效和毒副反应。结果观察组有效率76.0%,高于对照组的48.0%(P<0.05)。毒副反应发生率观察组低于对照组(P<0.05)。结论地塞米松联合沙利度胺治疗MM的疗效显著,患者耐受性好。     

改良VAD方案联合沙利度胺治疗多发性骨髓瘤

目的:观察改良VAD方案联合沙利度胺治疗多发性骨髓瘤的临床疗效和不良反应。方法:12例多发性骨髓瘤均采用改良VAD方案联合沙利度胺治疗。沙利度胺的起始剂量为100mg/天,每周增加100mg,直至剂量增加至300mg/天。28天为1周期。治疗2个周期后,根据血象、血清M蛋白、血清肌酐、骨髓瘤细胞等指标来判断疗效,分为部分缓解、改善和无效。结果:部分缓解6例,改善4例,总有效率为83·3%。主要不良反应有嗜睡(75%)、便秘(50%)、头晕(25%)和感染(25%),但都能耐受。结论:改良VAD方案联合沙利度胺治疗多发性骨髓瘤具有疗效高和耐受性好的优点,尤其是对于有合并症的老年患者是安全的,值得进一步的临床观察和推广。     

地塞米松联合沙利度胺治疗14例多发性骨髓瘤疗效观察

目的：观察大剂量地塞米松联合沙利度胺治疗多发性骨髓瘤（multiplemyeloma，MM）的疗效及不良反应。方法：地塞米松20mg／d-40mg／d，奇数月d1-4，d9-12，d17-20，偶数月d1-4，28天／疗程，联合或不联合沙利度胺100mg／d-200mg／d。判断疗效，同时观察血常规、肾功能、Ca^2＋、影像学等变化。结果：14例患者的总有效率（CR＋PR＋进步）为85．71％，总缓解率（CR＋PR）57．14％（8／14例），初发患者中总有效率达100％（8／8例），总缓解率达75．00％（6／8例），复发难治患者中总有效率66．67％（4／6例），总缓解率33．33％（2／6例）。主要副作用为感染、血压升高、血糖升高。结论：大剂量地塞米松联合沙利度胺是治疗多发性骨髓瘤的有效方案，毒性较轻。     

沙利度胺联合地塞米松治疗初发多发性骨髓瘤的临床观察

 目的 观察沙利度胺联合地塞米松治疗初发多发性骨髓瘤（MM）的疗效。方法 沙利度胺100 mg／d,每周增加50 ~ 100 mg／d,直到200 ~ 300 mg／d,维持治疗。地塞米松40 mg／d,第1 ~ 4天,第9 ~ 12天,第17 ~ 20天,28 d为1疗程。获完全缓解或部分缓解的患者,应用沙利度胺100 ~ 200 mg／d维持,每2个月应用地塞米松40 mg／d,第1 ~ 4天,冲击治疗1次。结果 21例初发MM 5例达完全缓解,12例获部分缓解,总有效率80.9 %。结论 沙利度胺联合地塞米松治疗初发MM疗效较好     

沙利度胺联合VAD方案治疗多发性骨髓瘤13例

目的探讨沙利度胺联合VAD方案治疗多发性骨髓瘤(MM)的疗效和毒副反应。方法回顾性分析13例初治MM患者的临床资料。结果全组13例患者的总有效率76.92%;1例头昏乏力,3例轻微胃肠道反应,1例骨髓抑制,患者均可耐受。结论沙利度胺联合VAD治疗初治MM患者有效,毒副反应轻。     

沙利度胺对难治、复发多发性骨髓瘤患者骨髓微环境的影响

背景与目的:越来越多的研究表明,骨髓瘤细胞的生长、生存以及耐药的产生与骨髓微环境密切相关。沙利度胺(thalidomide,Thal)是作用于骨髓微环境的药物之一,我们通过观察沙利度胺对难治、复发多发性骨髓瘤(multiplemyeloma,MM)患者骨髓微环境的影响,进一步了解Thal的作用机制。方法:用流式细胞仪检测沙利度胺治疗前后难治、复发的MM患者骨髓基质细胞膜表面的细胞间粘附分子(ICAM-1)和血管细胞粘附分子(VCAM-1)的表达强度,半定量RT-PCR法检测骨髓基质细胞IL-1βmRNA、IL-6mRNA、TNF-αmRNA的表达,采用酶联免疫吸附法(ELISA)测定其血清VEGF、bFGF水平。结果:难治、复发MM患者骨髓基质细胞(BMSC)膜表面ICAM-1、VCAM-1平均荧光强度分别为13.28±4.26、10.35±2.47,用Thal治疗有效的难治、复发MM患者BMSC膜表面ICAM-1、VCAM-1平均荧光强度分别为4.29±0.98、3.54±0.62,明显受抑制(P<0.05)。难治、复发MM患者BMSCIL-1βmRNA、IL-6mRNA、TNF-αmRNA与β-actin的比值分别为1.83±0.64、24.52±11.46、3.42±1.83,用Thal后有效的难治、复发MM患者BMSCIL-1βmRNA、IL-6mRNA、TNF-αmRNA与β-actin的比值分别为0.58±0.11、13.47±14.31、1.25±0.76,明显受抑制(P<0.05)。而治疗无效的难治、复发MM患者BMSC膜表面IC     

沙利度胺治疗难治性复发性多发性骨髓瘤的临床研究

目的：观察沙利度胺(Thalidomide，国内商品名：反应停)单药或联合地塞米松治疗多发性骨髓瘤(Multiple Myeloma，MM)的疗效及副作用。方法：单药组：男性13例，女性2例，中位年龄58岁。其中2例为初发的MM；1例为原发性浆细胞白血病(PCL)；12例为难治性MM，其中3例为自体外周血干细胞移植(AutoPBSCT)术后复发。反应停治疗起始剂量为100mg／d，根据患者耐受情况，逐渐加量，最高达800mg／d。联合组：男性20例，女性7例，中位年龄56岁。其中初发1例；1例为原发性PCL；25例为难治MM，其中2例为自体外周血干细胞移植(AutoPBSCT)术后复发。反应停剂量为400mg／d左右加用地塞米松40mg／天，第1～4天，第9～12天，第17～20天，1个月为一个疗程。结果：单药组42．9％(6／14)的患者对治疗有效，其中3例为完全缓解(CR)或接近完全缓解(Near-CR)，1例有明显治疗反应(Major response)，1例为部分缓解(PR)。12例难治性MM中4例有效(33．3％)；联合组有效率为57．7％(15／26)，其中4例为CR或Near-CR，2例有明显治疗反应，9例为PR。25例难治性MM中11例有效(44．0％)。两组间在总有效率及难治病例的有效率方面均无显著差异。两组患者均出现不同程度的便秘、皮疹等副作用，但均可耐受。结论：沙利度胺单药或联合地塞米松对难治性复发性MM均有效。     

Randomized Phase II trial of thalidomide alone versus thalidomide plus interferon alpha in patients with refractory multiple myeloma

The potential synergistic anti-myeloma effect for thalidomide combining with interferon alpha was not yet clear clinically. From March 2001 to January 2004, a total of 28 heavily pretreated multiple myleoma (MM) patients were enrolled in this open-labeled, randomized Phase II study. Patients with refractory MM were randomized to receive either thalidomide alone (200 mg/day up to the maximum dose 800 mg/day, arm B) or the combination of thalidomide and interferon alpha (3 MIU/m² subcutaneous injection 3 times weekly, arm A). The objective of this study was to compare the safety and efficacy of thalidomide alone to combined regimen. The patients' characteristics were similar between the 2 arms. However, the average treatment duration was significantly longer in the arm B than the arm A (236 days versus 101 days, p = 0.029). Serum levels of paraprotein decline ≥ 25 percent were obtained in 6 of 12 patients (50.0 percent) treated with arm B and 3 of the 16 patients (18.8 percent) treated with arm A. The estimated time to event was 7.9 months (95 percent confidence interval [95%CI], 0.5-15.4) for arm B and 1.5 months (95%CI, 0.0-3.4) for arm A (log-rank test, p = 0.0193). The major adverse events in both arms consisted of neutropenia, anemia, thrombocytopenia, constipation, somnolence, and skin rash. Our study showed that thalidomide alone was effective and tolerated in patients with relapsed or refractory MM. The thalidomide combined with interferon alpha resulted in a lower frequency of paraprotein response, shorter treatment-duration and 25 percent of patients' refusing rate. It may be concluded that the combined regimen is not well tolerated in our patients and needed to be further evaluated in the future.     

砷剂在复发难治多发性骨髓瘤中的应用

目的 探讨砷剂在复发难治多发性骨髓瘤(MM)中的治疗价值及不良反应.方法 回顾性分析21例复发难治MM患者临床资料,其中10例采用砷剂治疗(亚砷酸组),11例接受既往未使用过的方案治疗或应用含有新药(如硼替佐米)方案治疗(对照组).亚砷酸组中,男性5例,女性5例,平均年龄(62±5)岁;对照组中,男性7例,女性4例,平均年龄(59±9)岁.每2个疗程观察总有效率和总生存(OS)时间.结果 亚砷酸组与对照组的中位显效时间分别为8.00个月(6.00~9.00个月)和3.50个月(1.00~24.00个月),总有效分别为3例(3/10)和6例(6/11),两组总有效率差异无统计学意义(P=0.245);两组不良反应发生率差异无统计学意义(P>0.05).亚砷酸组中位OS时间10.00个月(8.00~24.00个月),对照组为6.00个月(1.00~69.00个月),两组差异无统计学意义(P=0.900).结论 亚砷酸方案治疗复发难治MM不良反应未增加,性价比高.     

亚砷酸联合沙利度胺治疗难治性复发性多发性骨髓瘤的疗效

 【摘要】　目的　观察亚砷酸（ATO）联合沙利度胺治疗难治性复发性多发性骨髓瘤（MM）的疗效和安全性。方法　35例难治性复发性MM患者,给予ATO（10 mg／d）及维生素C（2 g／d）静脉滴注,连续应用14 d,每28 d为1个疗程;同时给予沙利度胺口服,起始剂量为50 mg／d,1周后逐步加量并调整至100～150 mg／d,长期维持。连续应用3个疗程后评估疗效和患者不良反应,有效患者继续沙利度胺维持治疗,并随访观察无进展生存（PFS）。采用参照欧洲血液和骨髓移植小组骨髓瘤疗效判定标准判定疗效,并按世界卫生组织（WHO）标准判定不良反应。结果　ATO联合沙利度胺治疗难治性复发性MM总有效率71.43 %（25／35）,完全缓解2例（5.71 %）,部分缓解12例（34.29 %）,微小反应 11例（31.43 %）,无效10例（28.57 %）。25例患者进入维持治疗后,中位随访期为11个月（2～31个月）,中位PFS 9个月。主要不良反应有消化道反应、白细胞减少、肝功能损害、手足麻木等,不良反应轻微,均可耐受。结论　ATO联合沙利度胺治疗难治性复发性MM有效、可行,并有较好的治疗顺从性。     

Effect of different doses of dexamethasone combined with bortezomib and thalidomide in treatment of elderly patients with multiple myeloma

Objective: To observe the efficacy and safety of different doses of dexamethasone combined with bortezomib and thalidomide in the treatment of elderly patients with multiple myeloma (MM). Methods: A total of 33 elderly MM patients treated in Shanghai Fifth People's Hospital between August 2014 and August 2019 were enrolled in the study. According to the dosage of dexamethasone, the patients were divided into the observation group (low dose dexamethasone, 20 mg/d on day 1-4, and 11-14) and the control group (high dose dexamethasone, 40 mg/d on day 1-4, 9-12, and 17-20). Twenty-eight days was a course of treatment. The clinical efficacy and safety of patients was assessed after 4 courses of treatment. The patients were followed up till June 30th, 2021. Kaplan-Meier and log-rank were used to analyze the survival. Results: The overall response rate (ORR) and median overall survival (OS) were not significantly different between the observation and control groups (82.4% vs 87.5%, P=0.973; 58 months vs 61 months, P=0.859). The incidence rates of lung infection and hyperglycemia in the observation group were both significantly lower than those in the control group (both P< 0.05). Conclusions: Different doses of dexamethasone combined with bortezomib and thalidomide have definite curative effects in the treatment of elderly MM patients. But low dose dexamethasone has fewer adverse reactions and better safety. © 2022, The Second Affiliated Hospital, College of Medicine, Zhejiang University.. All right reserved.     

Previous thalidomide therapy may not affect lenalidomide response and outcome in relapse or refractory multiple myeloma patients

Introduction

Lenalidomide is a thalidomide analogue, designed to have improved efficacy and tolerability over the parent drug. The aim of this retrospective analysis is to evaluate the impact of thalidomide therapy on lenalidomide response and outcome in relapse or refractory multiple myeloma patients.

Patients and methods

A total of 106 relapsed or refractory multiple myeloma patients received lenalidomide 25 mg plus dexamethasone as salvage therapy; 80 patients progressed on thalidomide treatment (thalidomide-resistant) and 26 patients discontinued thalidomide in at least partial remission (thalidomide-sensitive). Median time from diagnosis to lenalidomide treatment was 57 months. Median prior lines of therapies were 3, range 1-6. 62% of patients were previously treated with autologous stem cell transplantation, and 71% with bortezomib-based regimens.

Results

In the thalidomide-resistant and -sensitive groups, the at least partial response rates were 56.2% and 61.5% (P = .45), including at least VGPR rates of 16.2% and 11.5%; the median progression free survival was 10 and 12 months (P = .12) and the median overall survival was 17 and 18.5 months (P = .50), respectively.

Conclusion

Lenalidomide may be equally effective in heavily pre-treated multiple myeloma patients who are thalidomide-resistant or thalidomide-sensitive to a previous therapy.     

沙利度胺联合MP方案治疗多发性骨髓瘤的疗效评价

 目的　比较沙利度胺联合美法仑+泼尼松方案（MPT）与美法仑+泼尼松方案（MP）治疗多发性骨髓瘤（MM）的疗效与患者不良反应。方法　采用回顾性分析,MPT组26例,美法仑每天9 mg／m2口服,第1天至第4天,泼尼松60 mg／m2,第1天至第4天,或者美法仑每天4 mg／m2口服,第1天至第7天;泼尼松每天40 mg／m2口服,第1天至第7天,28 d为1个疗程,沙利度胺自化疗开始持续给药,100～200 mg／d,每4周为1个疗程,MP组21例,美法仑及泼尼松用法用量同MPT组,6个疗程后评价总疗效。结果　MPT组的总有效率（ORR）为65.4 %,明显高于MP组的42.9 %（P＞0.05）;MPT组中位反应时间为2个月,MP组为3个月;MPT组患者治疗后血红蛋白及清蛋白升高明显高于MP组（P＜0.05）;MPT组不良反应的发生率高于MP组（P＜0.05）,但两组3度以上的不良反应差异无统计学意义;MPT组中位无进展生存时间（PFS）为11个月,2年PFS为66.18 %。结论　与MP方案相比,MPT方案可以提高MM患者的有效率,改善生活质量,延长生存时间,耐受性良好。     

Low dose thalidomide in patients with relapsed or refractory multiple myeloma

Remarkable results of the treatment of refractory multiple myeloma with thalidomide have been reported. In most preceding studies, the given thalidomide dose was escalated to a maximum tolerated dose of up to 800 mg/d. The frequency of adverse effects correlates with dose intensity. Since a significant gain of therapeutic effects could not be observed as thalidomide dosage was escalated, the optimal dose of thalidomide remains to be determined. We report the results of a study with low dose thalidomide (median administered dose 100 mg/d, range 50-400 mg/d). Twenty-four relapsed (n=19) or resistant (n=5) multiple myeloma patients were included in the study. Twelve patients (50%) received thalidomide as monotherapy, 8 patients (33%) received a combination of thalidomide and dexamethasone (every 4 weeks 40 mg/day for 4 days) and 4 patients (17%) who were resistant to vincristine, doxorubicin, dexamethasone (VAD) received VAD combined with thalidomide. Overall, a response was observed in 12 patients (50%). Of the 12 patients treated with low dose thalidomide alone 5 (42%) responded, of the 8 patients who received a combination of thalidomide and dexamethasone 5 (63%) responded and of the 4 patients who had thalidomide in addition to VAD 2 patients (50%) responded. In 3 patients, thalidomide treatment had to be discontinued because of side effects and 1 patient died before response could be assessed. We conclude that low dose thalidomide is an effective and safe rescue therapy in relapsing or refractory multiple myeloma. Response to thalidomide might be dependent on prognostic parameters and tumor burden. To answer these questions larger prospective studies are necessary.     

The place of thalidomide in the treatment of multiple myeloma

Thalidomide represents the first attempt in multiple myeloma (MM) patients to overcome resistance to chemotherapy through a biological agent. The exciting results reported in the first study by Singhal et al. in 1999 [1] led to several other studies which aimed to evaluate its efficacy in different settings and disease phases, to define its toxicity, and to establish the optimal dose. Some of these questions have already been answered while others, such as the best dosage or the best schedule to obtain the highest efficacy with the lowest toxicity, still remain. Thalidomide has been studied as a single agent or in association with other drugs (dexamethasone, chemotherapy and new drugs) showing a synergic activity. We review the results of the main studies on the efficacy and toxicity of thalidomide used as a single agent or in association with other drugs, reflect on its present role, and consider its future contribution to the treatment of MM.     

新药治疗复发难治性多发性骨髓瘤的研究进展

复发难治性多发性骨髓瘤（MM）是血液系统恶性肿瘤治疗的难点.由于耐药现象的广泛存在,复发难治性MM治疗方案的选择较初治者有着更多影响因素,且疗效较差.文章分别评价了沙利度胺、来那度胺、硼替佐米等新药治疗复发难治性MM的单药及联合用药的疗效及相关不良反应,并报道了正在进行研究的新药的临床试验结果.