三氧化二砷联合维生素C治疗难治或复发性多发性骨髓瘤临床研究

目的：探讨三氧化二砷（As2O3）联合维生素C（VitC）治疗难治或复发性多发性骨髓瘤（MM）的疗效及不良反应.方法：对31例难治或复发性MM患者，采用As2O310 mg加5%葡萄糖溶液500 ml，静脉滴注，每日1次;VitC 1000 mg加5%葡萄糖溶液100 ml，静脉滴注，每日1次;1疗程为28 d.根据血清M蛋白及骨髓瘤细胞减少情况判断疗效，分为部分缓解、进步、无效.同时观察MM患者贫血程度、骨髓瘤细胞百分率、肾功能及血电解质等指标的变化.结果：部分缓解5例，进步11例，无效15例，总有效率为51.6%.主要不良反应为疲劳、恶心、呕吐.结论：As2O3联合VitC治疗难治或复发性MM疗效显著，不良反应轻，患者易耐受。     

沙立度胺联合MP化疗方案治疗多发性骨髓瘤23例

目的：观察沙立度胺联合MP方案治疗多发性骨髓瘤的疗效及其不良反应。方法：确诊的多发性骨髓瘤患者23例。沙立度胺-MP方案：沙立度胺自MP方案开始持续给药，每晚睡前口服，剂量从每天100mg开始，每周日剂量递增50mg，至患者不能耐受或最高至每日400mg；MP方案每月1个疗程。结果：部分缓解16例（69．6％），进步4例（17．4％），总有效率为87．0％（20／23）。有效的患者中10例在4周内起效，沙立度胺每天100～400mg，中位剂量每天225mg。常见的不良反应为皮疹、便秘、嗜睡、乏力、头昏、水肿等。结论：沙立度胺加MP方案治疗多发性骨髓瘤不良反应少，耐受性好，且反应率可能提高。     

腺苷蛋氨酸联合硫普罗宁治疗瘀胆型病毒性肝炎

目的观察腺苷蛋氨酸联合硫普罗宁治疗瘀胆型病毒性肝炎的疗效。方法30例患者用腺苷蛋氨酸冻干粉针剂1000mg加入5％葡萄糖250ml，静滴，1次／d，硫普罗宁冻干粉针剂200mg加入5％葡萄糖250ml，静滴，1次／d，对照组采用茵桅黄注射液30ml加入10%葡萄糖250ml中，静滴，1次／d，甘利欣注射液150mg加入10％葡萄糖250ml，静滴，1次／d。两组同时应用维生素、能量合剂、复方氨基酸等。疗程视黄疸消退情况而定，急性肝炎为2～4周，慢性肝炎为4～6周。同时观察患者治疗前后的症状和肝功能变化，并记录治疗过程中的不良反应。结果两组患者临床症状均消失，TBIL、DBIL、ALP、γ-GT值治疗前后差异有统计学意义（P〈0．01），ALT、AST值两组治疗前后差异无统计学意义（P〉0．05）。治疗组总有效率83．3％，优于对照组总有效率63．3％，两组结果差异有统计学意义（P〈0．01）。两组均无明显不良反应。结论腺苷蛋氨酸和硫普罗宁联用治疗瘀胆型病毒性肝炎具有明显的临床疗效。     

TAC方案治疗难治复发性多发性骨髓瘤17例

目的：评估沙利度胺、亚砷酸和维生素C（TAC）联合治疗难治复发性多发性骨髓瘤（MM）的有效性和安全性。方法：TAC方案治疗17例难治复发性MM。沙利度胺每晚睡前口服，初始剂量100mg／d，然后每周剂量递增50mg／d，维持剂量100～200mg／d（依病人耐受情况）；亚砷酸10mg／d，静脉滴注，亚砷酸结束后15min维生素C3g／d，静脉滴注，每周5次；用4周休2周为一疗程，连用3～6个疗程。结果：17例患者人组，14例可评估（3例因不良反应明显退出实验组）。完全缓解1例（7．14％），部分缓解3例（21．43％），进步6例（42．86％），无效4例（28．57％），总有效率71．43％，无严重不良反应，常见为乏力、便秘、水肿、皮疹、肝功能轻度异常等。结论：TAC方案治疗难治复发性MM有良好的耐受性和较少的不良作用，治疗顺从性好，有效率高。     

不同剂量三氧化二砷静滴联合适形放疗治疗中晚期原发性肝癌

目的观察不同剂量三氧化二砷联合三维适形放疗治疗中晚期原发性肝癌的疗效。方法将60例中晚期原发性肝癌患者随机分为四组各15例,对照组仅体外适形调强放射治疗;A组予三氧化二砷5mg静滴联合三维适形放疗;B组予三氧化二砷10mg静滴联合三维适形放疗;C组予三氧化二砷15mg静滴联合三维适形放疗。对四组疗效、生活质量、不良反应以及生存期进行比较。结果疗程结束后1个月,A、B、C组及对照组完全缓解分别为6、4、3、2例,部分缓解分别为6、5、5、2例,无变化分别为2、5、4、7例,进展分别为1、1、3、4例,有效率分别为80％、60％、53．3％、26．7％,A组与其他三组比较,P〈0．001。A、B、C组及对照组生活质量改善率比较差异无统计学意义。A、B、c组及对照组出现血液学毒性分别为2、3、6、4例;胃肠道反应分别为2、5、8、6例;肝损伤分别为1、3、5、3例;A组与其他三组比较,P〈0．05;C组与对照组比较,P〈0．05。生存曲线显示A组生存时间明显长于对照组和B、C组（P〈0．05）。结论小剂量（5mg）三氧化二砷静滴联合三维适形放疗治疗原发性中晚期肝癌患者效果好,不良反应少。     

小剂量三氧化砷联合化疗对复发或难治性骨髓瘤的疗效分析

多发性骨髓瘤（multiplemyeloma，MM）是多发于老年患者的造血系统恶性肿瘤，复发率高，缓解率低，而且易产生耐药性，预后不佳。自MP、VAD、M2及DCEP治疗方案应用于临床以来，虽然广大医务工作者作大量的工作，患者生存期一直未明显提高。近10余年来三氧化二砷（As2O3）治疗急性早幼粒细胞白血病获得了很大的成就。近年来As20，治疗多发性骨髓瘤也取得了较好的临床效果。     

As_2O_3为基础的联合方案治疗非霍奇金淋巴瘤

目的：评价三氧化二砷（As2O3）为基础的联合方案治疗非霍奇金淋巴瘤（NHL）的应用价值并探讨其作用机制，探索新疗法。方法：5例NHL患者应用亚砷酸注射液联合地塞米松、维生素C治疗，治疗过程中观察疗效及不良反应并动态监测血清VEGF、MMP-9含量变化。结果：5例患者中4例有效。所有患者均出现肝功能损伤，部分出现消化道症状、轻度血细胞下降、口周麻木等不良反应。3例B细胞型患者的VEGF值下降而2例富于T细胞的B细胞型患者上升，4例治疗有效患者MMP-9值下降而1例PD患者上升。结论：As2O3为基础的联合方案对NHL有一定治疗效果，通过下调VEGF、MMP9从而抑制血管新生可能是其作用机制之一。As2O3对VEGF水平的效应在不同细胞型NHL中可能不同而对MMP-9水平的效应与疗效相关。     

三氧化二砷联合化疗治疗难治性及复发性恶性血液病的临床疗效观察

目的 :观察三氧化二砷 (As2 O3 )联合化疗治疗难治性及复发性恶性血液病的疗效和不良反应。方法 :As2 O3 联合蒽环类药物、阿糖胞苷及足叶乙甙治疗难治性及复发性恶性血液肿瘤患者 33例 ,治疗方法是用As2 O3 (0 .1%溶液 ) 10ml加入 5 %葡萄糖溶液 5 0 0ml中静脉滴注 3～ 5h ,每天 1次 ,共治疗 30天 ;对复发性早幼粒细胞白血病、加速期慢性粒细胞白血病及骨髓增生异常综合征患者用As2 O3 联合柔红霉素 4 5mg·m-2 ·d-1× 3天加阿糖胞苷 10 0mg/m2 q12h× 7天治疗 ;对进展期多发性骨髓瘤和ⅢB～Ⅳ期非霍奇金淋巴瘤患者用As2 O3 联合米托蒽醌 8～ 10mg·m-2 ·d-1× 3天加足叶乙甙 6 0mg·m-2 ·d-1× 5天加Pred 1mg/kg× 7天加长春新碱 2mg× 1天治疗。结果 :33例患者中 ,19例获得完全缓解 (CR) ,2 7例有效 ,CR率为 5 7.8% ,有效率为 81.8%。结论 :As2 O3 联合化疗治疗难治性及复发性恶性血液病疗效好 ,不良反应少     

三氧化二砷联合VTD方案治疗多发性骨髓瘤的疗效观察

目的本研究观察三氧化二砷联合VTD方案化疗治疗初治多发性骨髓瘤（MM）的临床疗效。方法11例初治的多发性骨髓瘤（MM）患者,中位年龄62．6岁,最大年龄83岁,接受预先短程三氧化二砷（As203）再联合硼替佐米、沙利度胺、地塞米松（VTD方案）治疗,每例患者至少接受2—6个疗程的治疗。观察其总体有效率及毒副作用的发生情况。结果11例初治的患者中3例完全缓解（CR）,6例非常好的部分缓解（VGPR）,2例部分缓解（PR）。治疗后,总有效率达100％。最长随访治疗17个月,均保持持续缓解状态。主要不良反应包括周围神经症状、水肿、乏力和血小板减少,经对症治疗后均能改善,未发现严重毒副作用。结论三氧化二砷联合VTD方案化疗治疗初治的、尤其老年MM安全、有效,有良好治疗前景。     

小剂量沙利度胺联合VAD方案治疗多发性骨髓瘤26例临床观察

目的观察小剂量沙利度胺联合VAD方案化疗治疗多发性骨髓瘤的临床疗效及毒副作用。方法对26例多发性骨髓瘤患者,给予沙利度胺100mg／d联合VAO方案化疗,在化疗疗程结束后继续给予沙利度胺100mg／d维持治疗6个月以上。结果部分缓解15例,进步6例,无效5例,有效率为80．8％,不良反应轻,均可耐受。结论小剂量沙利度胺联合VAD方案化疗治疗多发性骨髓瘤安全有效。     

Phase II multicenter study of arsenic trioxide, ascorbic acid and dexamethasone in patients with relapsed or refractory multiple myeloma

Arsenic trioxide induces growth inhibition and apoptosis in multiple myeloma cell lines. Reducing glutathione by ascorbic acid may enhance the efficacy of arsenic trioxide. Here we report the results of an international multi-center study of arsenic trioxide in combination with ascorbic acid and dexamethasone as treatment for patients with advanced multiple myeloma.     

三氧化二砷联合化疗治疗难治复发多发性骨髓瘤的临床疗效分析

目的：分析三氧化二砷联合化疗治疗复发难治性多发性骨髓瘤(MM)的临床疗效。方法：收集复发难治性MM21例，分为原发难治性和复发难治性MM2组，应用三氧化二砷联合化疗，观察其总体和各组的有效率及副作用的发生情况。结果：治疗后，总有效率达90.5％，原发难治组及复发难治组的有效率分别为88．8％和91．7％。长期随访治疗7例，均保持持续缓解状态。未发现严重毒副作用。结论：三氧化二砷联合化疗治疗难治复发MM具有良好的疗效。     

酞胺哌啶酮联合环磷酰胺及地塞米松治疗难治复发性多发性骨髓瘤疗效观察

目的:评价酞胺哌啶酮(商品名:反应停)联合环磷酰胺及地塞米松治疗难治复发性多发性骨髓瘤(MM)的疗效和不良反应。方法:12例难治复发性MM患者口服酞胺哌啶酮350-400 mg／d,环磷酰胺50 mg／d,地塞米松40 mg／d(第1个月第1-4天,第9-12天,第17-20天,第2个月第1-4天,第9-12天;以后每月服第1-4天)。观察有效率、效应发挥时间、生存时间及不良反应。结果:完全缓解2例,部分缓解3例,进步1例,无效6例,有效率50．0％;效应时间为2-6个月,平均3．5个月;生存时间为8-34个月。不良反应多能耐受,末梢神经炎发生率100％(12／12),窦性心动过缓发生率为50．0％(6／12),便秘为66．7％(8／12),肺栓塞8．3％(1／12),粒细胞减少16．7％(2／12),感染16．7％(2／12)。结论:酞胺哌啶酮联合环磷酰胺及地塞米松治疗难治复发性MM有效,安全,平台期时间长,不良反应较轻。     

Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma

Despite aggressive and innovative therapy, patients with multiple myeloma (MM) invariably relapse and die of their disease. New options for non-cytotoxic salvage therapy and additional therapeutic strategies are needed. Arsenic trioxide, an antitumour agent with a multifaceted mechanism of action, induces apoptosis in vitro in MM cell lines and freshly isolated cells from MM patients and, in preliminary studies, displayed clinical activity in patients with late-stage MM. A phase 2, multicentre, open-label study of arsenic trioxide was conducted in 24 MM patients; eight had relapsed and 16 were refractory to prior therapy. Patients received arsenic trioxide 0.25 mg/kg/d for 5 d/week during the first 2 weeks of each 4-week cycle. Sixteen patients had grade 3 or 4 neutropenia and one required antibiotics. Reductions (25% or more) in serum M-protein levels occurred in eight of 24 (33%) patients. An additional six (25%) patients had stable disease. The median time to response was 67.5 d, with a median duration of response of 130 d. Arsenic trioxide therapy lowered serum creatinine levels in two patients with high baseline values. These data indicate that arsenic trioxide is active and reasonably well tolerated as a single-agent salvage therapy, even in patients with late-stage, relapsed and refractory MM.     

亚砷酸治疗老年恶性血液病的初步观察

目的探讨亚砷酸治疗老年恶性血液病的临床疗效及不良反应。方法对40例≥60岁的恶性血液病患者,应用亚砷酸治疗(10mg/d,静脉滴注,28d为1疗程,如不良反应明显则改为14d短疗程,间隔14d后再用14d,2次为1疗程)。观察其临床疗效及不良反应。结果急性早幼粒细胞白血病(APL)完全缓解(CR)8例,其他急性非淋巴细胞白血病(ANLL)CR1例,部分缓解(PR)1例,未缓解(NR)6例;慢性粒细胞白血病(CML)PR4例,NR2例;慢性淋巴细胞白血病(CLL)CR1例,PR1例;B细胞非霍奇金淋巴瘤(NHL)CR1例,PR2例,进步1例,无效1例;骨髓增生异常综合征(MDS)PR2例,进步2例,无效1例;慢性粒单细胞白血病(CMML)CR2例,PR2例;多发性骨髓瘤(MM)PR1例,进步1例。所有病例总有效率为75%。仅2例因严重肝损害、骨髓抑制而停药,无用亚砷酸相关死亡病例。结论对不能耐受强化疗的老年难治、复发的血液肿瘤患者,亚砷酸具有一定的治疗效果,且不良反应相对较低。     

Thalidomide treatment for immunoglobulin D multiple myeloma in a patient on chronic hemodialysis

A 64-year-old Japanese man suffering from IgD lambda myeloma and renal failure requiring chronic hemodialysis was treated with thalidomide. Serum IgD concentration was 4,050 mg/dl and myeloma cells constituted 95.6% of nucleated cells in bone marrow at the start of treatment. These parameters improved markedly to 1,590 mg/dl and 22.0%, respectively, in the 4 months immediately prior to his death due to pneumonia. Thalidomide caused peripheral neuropathy and constipation at a dose of 100 mg daily in the first week of treatment, but adverse effects resolved upon dose reduction. Thalidomide represents a valid therapeutic option for some myeloma patients receiving hemodialysis.     

Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single-arm study

We assessed the safety and efficacy of melphalan, arsenic trioxide (ATO) and ascorbic acid (AA) (MAC) combination therapy for patients with multiple myeloma (MM) who failed more than two different prior regimens. Patients received melphalan (0.1 mg/kg p.o.), ATO (0.25 mg/kg i.v.) and AA (1 g i.v) on days 1-4 of week 1, ATO and AA twice weekly during weeks 2-5 and no treatment during week 6 of cycle 1; during cycles 2-6, the schedule remained the same except ATO and AA were given twice weekly in week 1. Objective responses occurred in 31 of 65 (48%) patients, including two complete, 15 partial and 14 minor responses. Median progression-free survival and overall survival were 7 and 19 months respectively. Twenty-two patients had elevated serum creatinine levels (SCr) at baseline, and 18 of 22 (82%) showed decreased SCr levels during treatment. Specific grade 3/4 haematological (3%) or cardiac adverse events occurred infrequently. Frequent grade 3/4 non-haematological adverse events included fever/chills (15%), pain (8%) and fatigue (6%). This steroid-free regimen was effective and well tolerated in this heavily pretreated group. These results indicate that the MAC regimen is a new therapeutic option for patients with relapsed or refractory MM.     

Thalidomide treatment of resistant or relapsed multiple myeloma patients

BACKGROUND AND OBJECTIVES: Thalidomide is currently used as a very promising drug in patients with recurrent multiple myeloma or those refractory to chemotherapy. Literature data show prolonged survival in patients with advanced multiple myeloma treated with thalidomide but the optimal time and dose of thalidomide treatment remain to be established. DESIGN AND METHODS: We have treated 53 refractory or relapsed myeloma patients with thalidomide (Grunenthal, Aachen). The patients received thalidomide orally as monotherapy at a starting dose of 200 mg daily, with a dose increase of 100 mg every week to a maximum well-tolerated dose of 400 mg. All the patients qualified for the therapy underwent clinical and laboratory assessments every 4 weeks. Laboratory tests included complete blood count, electrophoresis, immunoglobulin level, lactate dehydrogenase (LDH), C-reactive protein, b2 microglobulin concentration, liver and renal function tests and there was also a monthly neurological examination. Bone marrow aspiration was performed every 3 months during the 12-month treatment. RESULTS: Among 53 evaluable patients, a clinical response was observed in 27 (51%): there was a major response in 7 patients, a partial response in 12 and a minor response in 8. INTERPRETATION AND CONCLUSIONS: In responding patients the earliest response was observed after 4 weeks of treatment and the latest after 12 weeks of treatment. Our results, obtained during a long observation period, show that thalidomide is an effective drug, with an acceptable degree of toxicity, in patients with refractory multiple myeloma.