沙立度胺联合化疗治疗难治性及复发性多发性骨髓瘤的临床观察

目的观察沙立度胺联合化疗治疗难治性复发性多发性骨髓瘤(multiple myelo-ma,MM)的疗效及不良反应;研究MM患者血浆脑源性神经营养因子(brain-derived neuro-trophic factor,BDNF)、血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的表达及动态变化。方法应用沙立度胺起始剂量100mg,每晚顿服或早晚各1次,每2周增加1次剂量为200mg/d,直至剂量达到600mg/d,依此剂量维持治疗并同时联合化疗治疗48例MM患者。根据血清M蛋白及骨髓中骨髓瘤细胞减少情况判断疗效。用酶联免疫吸附试验(ELISA)方法测定对照组、MM患者血浆BDNF、VEGF的浓度及其治疗前、后的变化。结果48例患者部分缓解24例,进步14例,总有效率79.1%(38/48),无不能耐受的不良反应;患者血浆BDNF、VEGF治疗前分别为(4.16±0.75)μg/L、(138.35±22.78)ng/L,与正常对照组(1.97±0.43)μg/L、(56.83±13.76))ng/L相比,差异均有统计学意义,t=12.21,P=0.001;t=14.87,P=0.001。38例MM患者血浆BDNF、VEGF水平治疗后(2.34±0.56)μg/L、(89.25±20.70)ng/L较治疗前(4.32±0.75)μg/L、(154.07±22.40)ng/L明显下降,差异有统计学意义,t=4.70,P=0.001;t=3.45,P=0.001。结论MM患者血浆BDNF、VEGF明显升高,经治疗后两者均明显下降。血浆BDNF、VEGF水平可能为MM促进血管新生的细胞因子。沙立度胺联合化疗治疗难治性、复发性MM疗效可靠。     

Beneficial effect of high-dose chemotherapy in multiple myeloma patients with unfavorable prognostic features.

It has been established that high-dose chemotherapy (HDT) improves the therapeutic outcome of patients with multiple myeloma (MM) as compared with standard-dose therapy (SDT); however, little is known about the impact of HDT on different prognostic groups of MM patients. We therefore compared the survival times of 77 patients with previously untreated MM who were enrolled in HDT regimens with those of 64 similar patients <65 years old, who would be eligible for HDT but were treated by SDT. Overall, HDT was superior to SDT with respect to achievement of complete remissions (28% versus 2%; P <0.0001) and improvement of progression-free survival (PFS) (30.2 versus 21.2 months; P = 0.01) as well as overall survival (OS) (median 54.9 versus 49.4 months; P = 0.048). According to the chromosome 13q14 status as determined by fluorescence in situ hybridization and serum levels of beta(2)-microglobulin (beta(2)M), MM patients were separated into a standard-risk group (normal chromosome 13q14 and beta(2)M 4 mg/l). Among patients of the high-risk group, both PFS (26.4 versus 10.7 months; P = 0.004) and OS times (40 versus 23 months; P = 0.05) were longer in patients receiving HDT compared with patients treated by SDT. In the standard-risk group, PFS and OS times were not significantly different between HDT patients and SDT patients. Results of this retrospective analysis suggest that the beneficial effects of HDT are greater in MM patients with high-risk features than in patients with absence of such poor prognostic indicators.     

低剂量沙利度胺联合常规化疗治疗多发性骨髓瘤的疗效观察

目的观察多发性骨髓瘤行低剂量沙利度胺联合常规化疗的疗效。方法选择2008年2月至2014年1月间收治的56例多发性骨髓瘤患者,随机分为观察组和对照组,每组28例。两组多发性骨髓瘤患者均采取常规化疗,观察组再联合低剂量沙利度胺。观察两组临床病理特征,监测患者的血常规、24 h尿蛋白、血清单克隆免疫球蛋白、骨骼X线平片情况,记录不良反应。结果观察组多发性骨髓瘤患者的总有效率为89.3%,高于对照组的64.3%(P=0.027);观察组患者的无进展生存时间、总生存期均长于对照组(P<0.001)。两组多发性骨髓瘤患者的治疗效果和预后情况差异有统计学意义(P<0.050)。结论对于多发性骨髓瘤的患者,采取低剂量沙利度胺联合常规化疗的方式,能够获得显著的治疗效果,保证较好的预后。     

Risk factors for relapse after complete remission with high-dose therapy for multiple myeloma

Complete remission (CR) is an important surrogate for long-term survival for patients with multiple myeloma. However, most patients achieving CR eventually relapse and die from their disease. To better define the predictors of relapse, we conducted a retrospective review of outcomes for patients who achieved CR after autografting at our institution. From January 1990 to December 2002, among >400 patients transplanted, 81 (54 males and 27 females) achieved CR. With a median follow up of 58 months for all surviving patients, the 5-year progression-free survival (PFS) was 33% [95% confidence interval (CI) = 23 - 44] and 5-year overall survival (OS) was 67% (95% CI = 54 - 77). Median PFS was 37 months and median OS has not yet been reached. On multivariate analysis, high tumor mass at diagnosis emerged as a predictor of poor outcome. We conclude that high tumor mass at diagnosis predicts a significantly shorter remission duration for myeloma patients undergoing autografting.     

低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤35例

 目的　观察低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤（MM）患者的疗效及安全性。方法　35例初治及难治复发MM患者,硼替佐米1.1 mg／m2,第0、3、7、10天,静脉注射;沙利度胺从50 mg／d开始逐渐加量至150 mg／d或患者能够耐受的最大剂量;化疗方案根据每疗程患者情况选择MP、VAD或AD方案。28 d为1个疗程,每例患者至少接受2个疗程以上治疗。达到部分缓解（PR）及以上疗效的患者应用沙利度胺150 mg／d或患者能够耐受的最大剂量维持治疗。采用2006年MM国际统一疗效标准观察疗效,根据国际癌症研究中心不良事件通用命名标准评估不良反应。结果　中位随访20个月,35例患者治疗总有效率82.8 ％,其中完全缓解（CR）率48.6 %,良好的部分缓解（VGPR ）率17.1 %,PR率17.1 %。3年预计无进展生存（PFS）和总生存（OS）率分别为60.92 %和72.41 %。达PR以上疗效患者的OS率高于未达PR患者,差异有统计学意义（P＝0.004）。初治及难治复发患者客观缓解率（ORR）及OS率差异无统计学意义。Ⅲ～Ⅳ度非血液学毒性主要包括乏力（3／35）、恶心、呕吐（8／35）、便秘（4／35）和周围神经病变（3／35）。Ⅲ～Ⅳ度血液学毒性为粒细胞缺乏（10／35）和血小板减少（8／35）。结论　低剂量硼替佐米联合沙利度胺及化疗治疗MM具有较好的疗效及安全性,沙利度胺维持治疗可延长患者PFS时间。     

酞咪哌啶酮联合化疗初治多发性骨髓瘤疗效观察

目的:探讨酞咪哌啶酮(thalidomide,商品名反应停)联合化疗初治多发性骨髓瘤(multiplemyeloma,MM)的初步疗效。方法:治疗组14例初治多发性骨髓瘤应用反应停起始剂量100mg/d~200mg/d,每2周增加100mg~200mg直到患者能够耐受,最大剂量不超过600mg/d,同时联合以马法兰为主的MP或M2方案化疗;对照组20例初治多发性骨髓瘤单用MP或M2方案化疗。观察比较两组的3个月有效率、1年无事件生存率(EFS)和2年总生存率(OS)。结果:有效(部分缓解加进步)率治疗组为85.7%,对照组为50%。1年EFS治疗组为71.4%,对照组为35%。2年OS治疗组为57.1%,对照组为25%。反应停治疗组副作用可以耐受,便秘最常见。结论:反应停联合化疗可提高初治MM的疗效和1年EFS、2年OS。     

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。     

Changing concepts in multiple myeloma: from conventional chemotherapy to high-dose treatment

The treatment of Multiple Myeloma (MM), a malignant plasma cell disorder has changed considerably over the past decade. It has been convincingly shown that intensive treatment supported by autologous stem cell reinfusion is superior to conventional chemotherapy with alkylating agents or vincristine, doxorubicin and dexamethasone (VAD) alone in terms of a more rapid response and a longer disease-free survival. However, cure is not achieved in the majority of patients. Several trials have therefore focussed on repeated intensive treatments in order to improve the survival of these patients. Other approaches are aimed at identifying patients on the basis of prognostic factors, who may benefit from high-dose therapy. This review discusses the recent developments in intensive therapy for multiple myeloma.     

沙利度胺联合改良VAD方案治疗多发性骨髓瘤临床疗效观察

目的:观察沙利度胺联合改良VAD方案治疗多发性骨髓瘤（MM）的临床疗效和不良反应。方法:MM患者79例,均给予沙利度胺联合改良VAD方案治疗。结果:第1疗程后79例患者中CR为12.66%（10/79）,总有效率为77.22%（61/79）;3疗程后79例患者中CR为40.51%（32/79）,总有效率为83.54%（66/79）。44例大于等于60岁患者中,CR为40.91%（18/44）,总有效率为84.09%（37/44）。35例小于60岁患者中CR为40%（14/35）,总有效率为85.71%（30/35）,两组患者经统计学检验临床疗效无显著性差异（P>0.05）。38例IgG型患者中CR为44.74%（17/38）,总有效率为92.11%（35/38）。23例IgA型患者中CR为39.13%（9/23）,总有效率为82.61%（19/23）。8例轻链型患者中CR为37.50%（3/8）,总有效率为75.00%（6/8）。10例不分泌型患者中CR为30.00%（3/10）,总有效率为70%（7/10）;各组患者经统计学检验临床疗效无显著性差异（P>0.05）。结论:沙利度胺联合改良VAD化疗方案治疗MM完全缓解率及总有效率高,对不同分型及年龄组患者疗效均显著,值得进一步临床观察和推广。     

Role of thalidomide in previously untreated patients with multiple myeloma

Thalidomide represents one of the most relevant therapeutic advances for patients with multiple myeloma over the last 10 years. Despite some toxicities, it has demonstrated significant efficacy in elderly patients, as well as in the setting of younger subjects receiving autologous stem cell transplantation. Here, we report and discuss the clinical results achieved with thalidomide alone or in combination with dexamethasone or other drugs, such as melphalan, cyclophosphamide, doxorubicin and bortezomib, in previously untreated myeloma patients.     

Role of thalidomide in previously untreated patients with multiple myeloma

Thalidomide represents one of the most relevant therapeutic advances for patients with multiple myeloma over the last 10 years. Despite some toxicities, it has demonstrated significant efficacy in elderly patients, as well as in the setting of younger subjects receiving autologous stem cell transplantation. Here, we report and discuss the clinical results achieved with thalidomide alone or in combination with dexamethasone or other drugs, such as melphalan, cyclophosphamide, doxorubicin and bortezomib, in previously untreated myeloma patients.     

低剂量沙利度胺联合常规化疗治疗多发性骨髓瘤的疗效观察

目的探讨多发性骨髓瘤采用低剂量沙利度胺与常规化疗联合治疗的临床效果。方法选取2015年11月至2017年11月间宝鸡市人民医院收治的100例多发性骨髓瘤患者,采用随机数表法分为常规组与联合组,每组50例。常规组患者采用常规化疗治疗,联合组患者采用低剂量沙利度胺与常规化疗联合治疗,比较两组患者的临床疗效及血清相关指标。结果联合组患者总有效率为82. 0%,常规组为56. 0%,两组比较,差异有统计学意义(P <0. 05)。治疗后,联合组患者血清M蛋白和骨髓浆细胞数(16. 5±5. 5)%和(4. 9±2. 2)%,均低于常规组的(28. 8±12. 1)%和(11. 0±5. 7)%,血红蛋白(97. 7±12. 3) g/L,高于常规组的(88. 7±11. 4) g/L,差异均有统计学意义(均P <0. 05)。结论多发性骨髓瘤采用低剂量沙利度胺与常规化疗联合治疗的临床效果显著,可改善实验室相关指标,值得推行。     

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。     

Low efficacy of thalidomide in improving response after induction in multiple myeloma patients who are candidates for high-dose therapy

Giving the impact of complete response (CR) on outcome of multiple myeloma patients addressed to high-dose melphalan, we explored the role of a pre-transplant intensification with 3 months thalidome plus dexamethasone therapy (Thal-Dex), after pulse-VAD induction. Seventy-four multiple myeloma patients (MM pts) uniformly treated, were retrospectively studied. The response rate after pulse-VAD were: CR 6%, VGPR 40%, PR 23%, MR 23%, and progression 8%. The response rate after Thal-Dex were similar: CR 11%, VGPR 39%, PR 17%, MR 9%, and progression 24%. Giving no advantage in terms of response rate with an additive toxicity, Thal-Dex does not seem useful for intensification before transplant.     

大剂量地塞米松联合硼替佐米及沙利度胺治疗多发性骨髓瘤合并肾衰竭的临床研究

 【摘要】　目的　观察以大剂量地塞米松为基础的常规化疗加用硼替佐米及沙利度胺治疗后对多发性骨髓瘤合并急性肾衰竭患者的影响。方法　对23例伴肾衰竭的新发骨髓瘤患者均采用大剂量地塞米松加用硼替佐米和沙利度胺治疗,观察患者在用药前后肾损害的改善情况。结果　严重肾衰竭的12例患者中逆转1例,好转6例,总有效率58.3 %;肾衰竭的11例患者中逆转4例,好转5例,总有效率81.8 %。全部病例总有效率69.5 %（16／23）。对原发病骨髓瘤治疗总有效率60.9 %（14／23）。中位显效时间为2个月（1～5个月）。3年总体生存率为56.5 %,中位生存期34.4个月。结论　大剂量地塞米松联合硼替佐米和沙利度胺对新发骨髓瘤患者的肾衰竭逆转率高,对原发病治疗效果较好,不良反应少、安全可靠、见效快,可作为一线治疗用药。     

Therapeutic application of thalidomide in multiple myeloma.

Treatment with thalidomide and dexamethasone was given to 26 patients with active, previously untreated multiple myeloma (MM). Thalidomide was administered in an initial dosage of 200 mg/d for 2 weeks and then increased as tolerated (in 200-mg increments at 2-week intervals) to a maximum daily dose of 800 mg. Dexamethasone was given orally in a dosage of 40 mg/d on days 1 through 4, 9 through 12, and 17 through 20 in odd cycles and 40 mg/d on days 1 through 4 in even cycles at monthly intervals. Response was defined as a decrease in serum and urine monoclonal (M)-protein by 50% or greater. Twenty (77%) of 26 patients with active MM exhibited a therapeutic response. Among the first seven patients treated with a thalidomide dose of 400 mg, grade III to IV skin toxicity developed in two. Drug titration was then stopped and the thalidomide dose maintained at 200 mg/d. Six (86%) of seven patients showed a response after thalidomide dose escalation, whereas 14 (74%) of 19 patients demonstrated a response with a constant thalidomide dose of 200 mg/d. Thalidomide alone produced a response in six (38%) of 16 patients with smoldering or indolent myeloma. The angiogenesis grade was elevated in only 8% of these patients. Thirty-two patients with relapsed myeloma were treated with thalidomide dosed at 200 mg/d, with 200-mg escalations every 2 weeks to a maximum daily dose of 800 mg. Prior chemotherapy had failed and five (16%) patients had experienced relapse following stem cell transplantation. Ten (38%) of the 26 patients who had received at least two cycles of therapy obtained a response.     

Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support

In a population-based study, the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age (risk ratio: 1.62; confidence interval [CI] 1.22–2.15; p=0.001). A study of health-related quality of life (HRQoL) was integrated in the trial, using the EORTC QLQ-C30 questionnaire. Of the 274 patients receiving intensive therapy 221 (81%) were compared to 113 (94%) of 120 patients receiving conventional melphalan-prednisone treatment. Prior to treatment, there were no statistically significant differences in any HRQoL score between the two groups. One month after the start of induction chemotherapy, the patients on intensive treatment had more sleep disturbance than the control patients. At 6 mo, corresponding to a mean of 52 d after high-dose melphalan, the patients on intensive treatment had moderately lower scores for global QoL and role and social functioning and there was also a significantly higher score for appetite loss. At 12 and 24 mo, the HRQoL was similar to that of the control patients. At 36 mo, there was a trend toward less fatigue, pain, nausea, and appetite loss in the intensive-treatment group. Thus, the 18 mo of prolonged survival seem to be associated with a good health-related quality of life. Despite the moderate HRQoL reduction associated with the early intensive chemotherapy phase, this treatment modality must be regarded as an important step forward in the care of multiple myeloma.