PT-VTD方案治疗多发性骨髓瘤疗效观察

目的研究帕米膦酸二钠及沙利度胺联合VTD方案治疗多发性骨髓瘤（MM）的疗效。方法将30例MM患者分成两组,对照组采用VTD方案,实验组采用帕米膦酸二钠及沙利度胺联合VTD方案。结果实验组完全缓解3例,部分缓解10例,有效率77.78%,明显优于对照组（P〈0.05）;骨痛程度减轻,骨痛缓解时间缩短（P〈0.05）。结论帕米膦酸二钠及沙利度胺联合VTD方案治疗MM疗效好,可有效改善骨痛,提高患者的生活质量。     

化疗与洛曲序贯应用治疗多发性骨髓瘤15例疗效观察

多发性骨髓瘤(MM)患者治疗后完全缓解率很低，如果不采取高剂量化疗联合造血干细胞移植技术治疗，其治疗有效率仅为50％～80％，并且在控制骨痛、骨质破坏方面，效果不佳。2001年5月至2003年5月，我们应用化疗加洛曲(氯屈磷酸二钠)序贯治疗MM患者15例，取得良好疗效。现报告如下。     

双膦酸盐药物治疗多发性骨髓瘤的进展

多发性骨髓瘤(MM)的主要临床表现与骨的缺失有关。目前临床上使用双膦酸盐来辅助治疗骨缺失。其中口服依替膦酸钠无效，口服氯屈膦酸钠能够减少溶骨性损害，静脉使用帕米膦酸二钠可以减轻骨痛，提高生存质量，还有可能提高生存率，佐拉膦酸钠和依班膦酸钠有可能产生更明显的临床疗效，但还需进行更多的临床试验。本文对上述药物治疗MM作一综述。     

轻链型多发性骨髓瘤并发周围神经病变1例

患者，男，47岁。因骨痛、低热9个月，颅骨、肩胛骨、骨盆多发性溶骨改变，于1993年12月在解放军总医院经骨髓及血浆蛋白免疫电泳检查诊断为多发性骨髓瘤轻链型，经化疗骨髓中浆细胞由80％降至10％，达部分缓解，骨痛症状于1994年9月消失。此后间断化疗(M2和VAD方案)及注射     

唑来膦酸联合化疗治疗乳腺癌骨转移临床观察

将38例乳腺癌骨转移患者随机分为治疗组(唑来膦酸 紫杉醇 顺铂)和对照组(单用唑来膦酸).治疗后,两组骨痛缓解率、生存质量改善率无统计学差异;治疗组骨转移灶修复率为52.7%,高于对照组的15.8%.认为采用唑来膦酸联合化疗治疗乳腺癌晚期骨转移患者效果较好,且毒副反应较小,值得临床推广应用.     

二氯化锶联合唑来膦酸对乳腺癌转移性骨肿瘤患者缓解骨痛及生活质量的影响

目的探究二氯化锶联合唑来膦酸对激素依赖型乳腺癌转移性骨肿瘤患者缓解骨痛及生活质量的影响。方法62例激素依赖型乳腺癌转移性骨肿瘤患者,按治疗方案不同分组,各31例。对照组以二氯化锶治疗,观察组在对照组基础上联合唑来膦酸治疗,随访3个月,对比两组病灶疗效、骨痛缓解情况以及生活质量评分(GQOLI-74)。结果观察组病灶治疗总有效率54.84%(17/31)高于对照组32.26%(10/31),但无差异(P0.05);骨痛缓解率64.52%(20/31)高于对照组38.71%(12/31)(P0.05);躯体功能、物质生活状态、心理功能、社会功能评分均高于对照组(P0.05)。结论二氯化锶联合唑来膦酸疗法能有效保护骨质,缓解骨痛症状,改善生活质量。     

18例多发性骨髓瘤临床分析

目的：探讨多发性骨髓瘤(MM)的临床特征。方法：回顾性分析18例MM患者临床资料。结果：①MM起病隐匿，临床表现多样化．易误诊；②大部分患者表现骨痛和贫血．免疫分型以IgG和IgA最常见；③COP／CTHPOP化疗方案治疗5例初治患者有效率达80％；①三氧化二砷治疗1例难治复发进展期的MM患者在2个疗程后取得完全缓解。结论：①中年以上不明原因的骨痛、贫血、反复感染、白蛋白正常而白球蛋白比例降低、蛋白尿、血沉快等应考虑MM可能，应作进一步检查；②COP／CTHPOP化疗方案对初治MM有较好疗效；③三氧化二砷可用于治疗难治复发的MM患者。     

VAD方案化疗联合血液净化治疗MMRN疗效及对血清Scr、BUA水平的影响

目的探究VAD方案化疗联合血液净化治疗多发性骨髓瘤肾病(MMRN)疗效及对血清肌酐(Scr)、血尿酸(BUA)水平的影响。方法 68例多发性骨髓瘤肾病患者依据建档顺序分组,各34例。两组均予以常规治疗,于此基础上对照组仅采用VAD方案化疗,观察组采用VAD方案化疗联合血液净化治疗,治疗3个月,对比两组治疗前后Scr、BUA、血钙水平,并统计临床疗效、不良反应发生情况。结果两组治疗前Scr、BUA、血钙水平无差异(P0.05);治疗后观察组Scr、BUA、血钙水平均低于对照组(P0.05);总有效率76.47%(26/34)高于对照组52.94%(18/34)(P0.05);两组不良反应发生率无差异(P0.05)。结论多发性骨髓瘤肾病患者联合应用VAD方案化疗与血液净化治疗效果显著,可有效降低Scr、BUA水平,改善肾功能,安全性较高。     

二膦酸盐治疗对骨质疏松性骨痛、骨密度、骨强度的疗效及安全性评价

目的 观察两种二膦酸盐药物在治疗妇女绝经后骨质疏松性骨痛、骨密度、骨强度及骨折中的作用，评价其疗效及安全性。方法 202例绝经后骨质疏松患者简单随机分成3组，阿仑膦酸钠(福善美)组65例、依替二膦酸盐(依膦)组67例和钙尔奇D(钙剂)组70例，治疗1年。治疗前后采用双能X线骨密度测量仪(DEXA)测量腰椎、髋部骨密度(BMD)及椎骨形态，桡骨、胫骨超声骨密度测定，检测血钙、磷、碱性磷酸酶(BAP)、尿I型胶元交联N端肽(NTX)。观察骨痛改善程度、骨量变化、骨强度改变、新骨折发生和不良反应。结果 福善美组和依膦组治疗后骨痛均明显改善，福善美组改善时间7～10天，依膦组约2周左右，钙剂组疼痛变化不明显。福善美组治疗12个月后骨量增加6．9％，依膦组增加3．9％，钙剂组减少0．3％。福善美组桡骨及胫骨超声声速(SOS)值分别增加0．8％和1．2％，依膦组变化不明显，钙剂组则分别下降0．5％和2．9％。福善美组无新骨折发生，依膦组有3例、钙剂组有5例发生新骨折。福善美组和依膦组不良反应主要为上消化道症状，依膦组较明显；钙剂组主要为便秘。结论 福善美能明显缓解骨质疏松性骨痛，显著提高骨密度，增加骨强度，预防骨质疏松性骨折的发生。     

唑来膦酸联合DP方案治疗非小细胞肺癌骨转移的疗效与安全性研究

目的研究唑来膦酸联合DP方案治疗非小细胞肺癌骨转移的疗效及安全性。方法将50例骨转移的非小细胞肺癌患者随机分为两组。治疗组接受唑来膦酸联合DP方案化疗,对照组为单纯DP方案。结果两组肺部原发病灶有效率(CR+PR)和总控制率(CR+PR+SD)差异无显著性;骨疼痛缓解率差异有显著性;骨病灶控制有效率(CR+PR)及总控制率(CR+PR+NC)差异均有显著性;不良反应轻微。结论唑来膦酸联合DP方案虽不能提高化疗疗效,但能有效缓解骨转移痛和控制骨转移灶,不良反应轻微,值得推广应用。     

pH is a potent modulator of erythroid differentiation

In patients with multiple myeloma, despite a major reduction of bone pain achieved with chemotherapy, skeletal disease continues to progress. The effects of clodronate, an inhibitor of osteoclastic bone resorption, are evaluated on the natural history of skeletal disease in patients with newly diagnosed multiple myeloma. Within the framework of the VIth MRC Multiple Myeloma Trial, 536 patients (218 women, 318 men) with recently diagnosed multiple myeloma were randomized to receive either clodronate 1600 mg daily ( n =264) or an outwardly identical placebo ( n =272) in addition to chemotherapy. Treatment with clodronate was associated with a 50% decrease in the proportion of patients with severe hypercalcaemia (5.1% v 10.1%, P =0.06) and a similar reduction in reported non-vertebral fractures (6.8% v 13.2%, P =0.04). Fewer patients receiving clodronate sustained vertebral fractures after entry to the trial (38% v 55%, P =0.01) and patients also lost less height over 3 years compared to those receiving placebo (2.0 v 3.4 cm, P =0.01). Biochemical indices of bone turnover were significantly lower in patients receiving concomitant clodronate, both at plateau and at disease relapse. The frequencies of back pain and poor performance status were significantly lower at 24 months in clodronate than in placebo-treated patients (10.9% v 19.9%, P =0.05, and 18.3% v 30.5% P =0.03 respectively.) There was no statistically significant difference in survival between the clodronate and placebo treated patients. The study indicates that long-term oral clodronate slows the progression of skeletal disease in multiple myeloma and decreases the associated morbidity. Patients without overt skeletal disease at diagnosis were also found to benefit from clodronate, indicating that this treatment should be initiated as early in the course of the disease as possible.     

Subgroup and cost-benefit analysis of the Finnish multicentre trial of clodronate in multiple myeloma

Osteolytic lesions and pathological fractures are the major problems in the clinical management of multiple myeloma. We previously reported the main results of a randomized, controlled multicentre trial in 350 Finnish patients with multiple myeloma. All patients received standard melphalan-prednisolone treatment and were randomized to receive either clodronate 2.4 g daily or a placebo for 24 months. The proportion of patients with progression of osteolytic bone lesions was twice as high in the placebo group as in the clodronate group (24.0%v 12.0%, P= 0.026). The purpose of the present study was to investigate factors associated with the progression of osteolytic lesions and to identify subgroups of patients who would benefit most from clodronate treatment. In univariate logistic regression analysis, including treatment (placebo, clodronate), sex, age, pain index, serum calcium and creatinine, myeloma stage, number of osteolytic lesions at baseline, and number of vertebral fractures at baseline as independent variables and the progression of osteolytic lesions as a dependent variable, only the treatment with a placebo was associated with the progression of osteolytic bone lesions. Separate analyses with respect to the progression of osteolytic bone lesions were carried out in the following subgroups: male v female, ± 64 v > 64 years, stage I v stage II-III myeloma, no osteolytic lesions at baseline versus osteolytic lesions at baseline, no vertebral fractures at baseline versus vertebral fractures at baseline, and a 50% treatment response to cytotoxic drugs versus no treatment response to cytotoxic drugs. The treatment with clodronate delayed the progression of osteolytic lesions similarly in these subgroups, with the exception of a subgroup of patients who did not have a 50% treatment response to cytotoxic drugs. The treatment with clodronate did not significantly increase treatment costs. We conclude that the treatment effect of clodronate seems to be independent of sex and age of the patients, the stage of myeloma, and the severity of bone lesions at diagnosis, but not of treatment response to cytotoxic drugs.     

Economic impact of using clodronate in the management of patients with multiple myeloma

The economic impact of using prophylactic clodronate as an adjunct to chemotherapy in the management of multiple myeloma for the first 4 years following diagnosis was established from the perspective of the National Health Service (NHS). A state-transition model of the course of multiple myeloma was constructed using the MRC VI myelomatosis trial results and information on patient management obtained retrospectively from clinical trialists. Data were collected on resource use and corresponding costs for standard management and managing severe hypercalcaemia, vertebral and non-vertebral fractures. Managing patients with prophylactic clodronate cost the NHS a mean 22 934 pound silver per patient; comprising 16 697 pounds silver for standard management, 4862 pound silver for clodronate therapy and 1376 pound silver for adverse events. Managing patients without prophylactic clodronate cost a mean 19 557 pound silver (16 697 pound silver and 2860 pound silver for standard management and adverse events respectively). Therefore prophylactic clodronate therapy increased the cost by 3377 pound silver, or 17% per patient. Hospitalization accounted for 32% of the total cost, whereas chemotherapy accounted for 5%. The results were robust to sensitivity analyses (range 2605 pound silver-4150 pound silver). Further studies are required to assess the impact of prophylactic clodronate on quality of life to enable the clinical benefits and additional cost of this treatment to be compared with other healthcare interventions.     

Bisphosphonate therapy in multiple myeloma: past,present, future

Bone disease characterised by osteolytic lesions, pathological fractures and hypercalcaemia is an important clinical feature in multiple myeloma. Pain, decreased performance status, and the need for palliative radiotherapy and surgical interventions are common sequelae. Bisphosphonates act primarily on osteoclasts to inhibit excessive bone resorption, and have therefore been investigated in myeloma patients to ameliorate the clinical consequences of the bone disease. Bisphosphonates are currently the therapy of choice in myeloma patients with hypercalcaemia. In long-term management, both oral clodronate and intravenous pamidronate are effective in reducing skeletal-related events. Zoledronic acid seems to be as effective as pamidronate. Whether bisphosphonates have antimyeloma activity is currently unknown. Cost-benefit analyses have shown reasonable efficacy with acceptable costs. Bisphosphonate therapy is now accepted as an important part of care in myeloma patients, although much still has to be learned in order to optimise this therapy in multiple myeloma.     

多发性骨髓瘤细胞遗传学变化及其蛋白酶体抑制剂的疗效观察

目的分析多发性骨髓瘤(MM)的细胞遗传学变化及其与蛋白酶体抑制剂治疗的关系。方法对2005年1月至2006年7月北京大学人民医院29例初诊的MM患者行染色体核型检查,采用骨髓细胞24h短期培养,用常规方法制备染色体,G显带进行核型分析。22例MM患者采用传统化疗即长春新碱联合阿霉素和地塞米松(VAD)方案或马法兰与泼尼松(MP)方案;7例患者应用蛋白酶体抑制剂(硼替佐米)为主的化疗方案。比较两组患者的有效率及缓解率。结果29例MM患者中异常核型检出率为37.9%,其中有复杂和高度复杂畸变的占81.8%。采用VAD或MP方案化疗的核型正常组的有效率为81.2%,核型异常组有效率为0,差异有显著性意义(P<0.05)。应用硼替佐米为主的化疗方案中核型异常组5例均有效,核型正常组2例均有效。核型异常组硼替佐米有效率与传统化疗组相比,差异有显著性意义(P<0.05)。结论染色体核型异常的患者,应首选蛋白酶体抑制剂硼替佐米等进行治疗。     

Established role of bisphosphonate therapy for prevention of skeletal complications from myeloma bone disease

Patients with advanced multiple myeloma (MM) often have increased osteolytic activity of osteoclasts and impaired osteogenesis by osteoblasts, resulting in osteolytic bone lesions that increase the risk of skeletal-related events (SREs) including pathologic fracture, the need for radiotherapy or surgery to bone, and spinal cord compression. Such SREs are potentially life-limiting, and can reduce patients' functional independence and quality of life. Bisphosphonates (e.g., oral clodronate and intravenous pamidronate and zoledronic acid) can inhibit osteoclast-mediated osteolysis, thereby reducing the risk of SREs, ameliorating bone pain, and potentially prolonging survival in patients with MM. Extensive clinical experience demonstrates that bisphosphonates are generally well tolerated, and common adverse events are typically mild and manageable. Studies are ongoing to optimize the timing and duration of bisphosphonate therapy in patients with bone lesions from MM.     

Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results

Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long‐term follow‐up in the Medical Research Council Myeloma IX study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg intravenously every 21–28 d) or clodronate (CLO; 1600 mg/d orally) plus chemotherapy. Among 1960 patients (5·9‐year median follow‐up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (ZOL 5·2% vs. CLO 5·8% at 2 years; incidence plateaued thereafter). The overall incidence of confirmed osteonecrosis of the jaw (ONJ) was low, but higher with ZOL (ZOL 3·7% vs. CLO 0·5%; P < 0·0001). ONJ events were generally low grade and most occurred between 8 and 30 months (median time to ONJ, 23·7 months). Among 10 patients with ONJ recovery data, four patients in the ZOL group completely recovered, two patients improved, and three patients experienced no improvement; one CLO patient experienced no improvement. Dental surgery or trauma preceded ONJ in six ZOL patients. The incidence of renal adverse events was similar for ZOL and CLO. ONJ incidence remained low and was lower with CLO compared to ZOL. We have seen no further ONJ cases to date.     

Long-term survival and prognostic factors in stage II-III multiple myeloma treated with conventional chemotherapy]

In this retrospective study, survival and prognostic factors were analysed in 65 patients with stage II-III multiple myeloma with osteolytic lesions. Multiple myeloma was diagnosed from 1976 to 1984, and patients were treated with conventional chemotherapy. The response rate to initial chemotherapy was 46%. The median survival time was 31 months. The 10-year survival rate was 10%. Four variables were individually prognostic: response to initial chemotherapy, bone marrow plasma cell percentage, the Durie and Salmon staging system, a biological staging system derived from Durie and Salmon's biological criteria regardless of bone lesions. In the multivariate analysis, only two prognostic variables were retained, namely the response to chemotherapy and the biological staging system. No prognostic value was observed for the extent of osteolytic lesions. This study suggests that, in conventionally treated multiple myeloma, long-term survival has improved compared with the previous decade. It also indicates that the extent of osteolytic lesions has little value for the definition of high-risk myeloma.     

Multiple myeloma causing obstructive jaundice by extramedullary plasmacytoma after Bence Jones protein loss--an autopsy case report

A 63-year-old man was admitted to our hospital with a chief complaint of general malaise in March 1986. A diagnosis of Bence Jones protein (kappa) type of multiple myeloma was made from increased atypical plasma cells in the bone marrow, urinary BJP (kappa) and osteolytic lesions. Urinary BJP (kappa) was decreased by MP and VENP therapies. In April 1987, he visited us again with the complaint of pain on the left shoulder. An examination revealed multiple osteolytic lesions and bilateral pleural effusion containing atypical plasma cells. Jaundice was developed at the end of July 1987. An ultrasound examination revealed a hypoechoic mass in the area of pancreatic head. The effusion was gradually increased without response to the treatment. He died of respiratory failure on July 31, 1987. On autopsy, extramedullary plasmacytoma was found in the head of pancreas. It was a rare case of multiple myeloma in which pleural effusion and multiple plasmacytomas, and finally obstructive jaundice were developed although urinary BJP (kappa) was reduced by treatment.     

Paget's disease with osteolytic lesions: combining medical and surgical treatments.

A patient with extensive Paget's disease of bone presented with severe bone pain, hypercalcaemia and a large osteolytic lesion of the femur which developed during long-term therapy with etidronate. Treatment with pamidronate normalized serum calcium concentration and induced a complete biochemical remission. The osteolytic lesion was grafted with bone chips. A recurrence of the Paget's disease was associated with clear autonomous hypercalcaemic hyperparathyroidism. Five years after removal of 3 1/2 hyperplastic parathyroid glands, the patient remains in complete clinical and biochemical remission. These findings illustrate the pitfalls encountered in the management of Paget's disease and the value of combining medical and surgical interventions.