多发性骨髓瘤预后因素筛选及分期比较

本研究旨在了解多发性骨髓瘤(MM)患者临床及实验室指标,寻找MM潜在预后因素,比较不同分期标准对疾病的分级情况。应用Kaplan-Meier法计算MM患者中位生存时间,Log-Rank法比较患者生存曲线。通过单变量及多变量分析评估MM患者潜在预后因素。对DS、ISS分期进行双变量相关分析。结果表明,MM患者中位生存时间42.7个月。影响MM患者生存的危险因素包括:Hb、Plt、Alb水平减低,血清LDH、Cr、CRP、β2-MG水平升高及骨髓中浆细胞数量增加,其中仅Hb水平对MM具有独立预后的预测价值。DS与ISS分期显著相关。DS分期中仅Ⅰ与Ⅲ期患者存在显著生存差异,而ISS分期中临床各期患者均存在显著生存差异。结论:Hb、Plt、Alb、LDH、Cr、CRP、β2-MG、骨髓中浆细胞数量对评估MM患者预后有一定临床价值。ISS分期标准可较好区分不同临床分期的MM患者。     

多发性骨髓瘤预后指标与Durie-Salmon分期和ISS分期的相关性分析

多发性骨髓瘤(MM)是以浆细胞异常增生为特征的恶性肿瘤性疾病,其临床表现复杂,影响预后的因素很多。该病的分期对于确定治疗策略是重要的,好的分期系统可以较好的预测患者的生存期,并可用于指导最佳治疗方案的选择。多发性骨髓瘤的分期方法较多,经历了较长时间的发展。1967年Carbone等提出根据危险因子(低血红蛋白、高血清尿素氮、高血清钙和行动受限)分期;     

多发性骨髓瘤的实验室诊断指标对临床治疗和预后的意义

目的探讨多发性骨髓瘤（MM）的常见实验室诊断指标对分型、治疗和预后的意义。方法观察40例MM患者骨髓细胞形态及细胞化学染色情况,并进行血清蛋白电泳、免疫固定电泳及血清β2-微球蛋白（β2-MG）、乳酸脱氢酶（LDH）检测。结果 MM患者的骨髓瘤细胞具有较高的异质性,酸性磷酸酶染色（ACP）,酸性α-醋酸萘酚酯酶染色（ANAE）,过典酸-雪夫染色（PAS）对骨髓瘤细胞分型具有鉴别诊断意义;血清蛋白电泳M蛋白检出率为84.0%,59.0%出现在γ区,25.0%出现于β与γ区间,16.0%出现于β区;免疫固定电泳对M蛋白检出率为95.0%,其中IgG型55.0%I、gA型25.0%、轻链型15.0%;LDH检测显示ISS分期Ⅰ期、Ⅱ期、Ⅲ期对应MM患者的LDH平均值分别为198.70 U/L2、32.34 U/L3、61.67 U/L,与血清β2-MG有较好的平行性。结论骨髓细胞形态与细胞化学染色对MM有鉴别诊断意义;免疫固定电泳对M蛋白检出率高于血清蛋白电泳,且前者对MM的临床分期及预后更具有临床意义;血清β2-MG与LDH的含量与MM患者病情呈正相关,可作为临床疗效及预后判断指标。     

123例多发性骨髓瘤患者的预后因素分析

目的评价生物学因素及治疗相关因素对多发性骨髓瘤（MM）患者的预后价值。方法生存分析采用Kaplan—Meier方法，各组之间生存的比较采用fog—rank检验；COX回归分析用于评估独立预后因素。结果①单因素分析显示：骨髓活检以原始幼稚浆细胞增生为主、C反应蛋白（CRP）〉8．0mg／L、瘤细胞表达CD117、血清β2-微球蛋白（β2-MG）3．5—5．5mg／L、染色体克隆性异常、13号染色体异常（A13）、亚二倍体、化疗无效以及IFN应用不足6个月与较短的总体生存（OS）时间相关（P值均〈0．05）；骨髓活检以原始幼稚浆细胞增生为主、初诊时有溶骨性损害、血清β2-MG3．5～5．5mg／L、存在染色体克隆性异常、A13、亚二倍体、化疗无效、应用IFN不足6个月与较短的疾病进展时间（TTP）相关（P值均〈0．05）。②多因素分析显示IFN应用超过6个月有助于延长患者OS时间及TTP；而骨髓活检显示以原始幼稚浆细胞增生为主为TTP的独立不良预后因素。结论骨髓瘤细胞形态特征有助于评估MM患者的预后，而IFN应用超过6个月有助于延长患者的OS时间与TTP。     

Chemotherapy for multiple myeloma

The combination of the melphalan and prednisolone (MP) can induce objective responses in about 50% of patients with multiple myeloma (MM) since its introduction in 1960. Since then many combination chemotherapy regimens have been used, but a large metaanalysis showed that the combination of oral MP is as effective as combination regimens including intravenous drugs. In recent years, many novel agents (including bortezomib, thalidomide, and liposomal doxorubicin) have been developed for the MM treatment. More recently, MP has been used in combination with these novel agents. The combination treatment of MP and thalidomide, overall survival was significantly better than seen in the MP treatment. In the near future, primary induction therapy will be changed.     

Classification and staging of melanoma

Although a standardized and uniformly accepted cancer staging system is an essential and fundamental requirement to enable meaningful comparisons across patient populations, the sometimes capricious biologic behavior of melanoma makes developing such a staging system particularly difficult. Since the earliest well-documented attempts at classifying patients with cutaneous melanoma were described more than 50 years ago, the identification of increasingly powerful prognostic factors has led to sequential modifications of the cutaneous melanoma staging system. The current AJCC staging system is based on relatively well-established prognostic factors; however, several recent reports have identified additional prognostic factors not included in the current system, and other studies support the re-evaluation of some of the currently employed staging criteria. Some of the more controversial areas include the relevance of level of invasion versus tumor thickness, optimal cutoffs for tumor thickness, importance of ulceration, the grouping of satellites with in-transit metastases, the inclusion of microsatellites and local recurrences as a separate staging criterion, the replacement of size of nodal mass with number of positive nodes, the importance of nodal metastases in more than one nodal basin, and the prognostic significance of distant metastases. Future modifications of the staging system are anticipated to better incorporate these observations. Stage-specific staging recommendations for the patient with melanoma provide the clinician with a framework to most efficiently assess extent of disease in an era of cost-conscious clinical practice. In the asymptomatic patient with primary melanoma (stage I or II), we recommend a chest roentgenogram and evaluation of alkaline phosphatase and LDH levels; extensive radiologic evaluations are not indicated, because the rate of detection in this population is extremely low. Additional staging information should also be obtained by the technique of lymphatic mapping and sentinel lymphadenectomy. For patients with local-regional disease (stage III, satellites, and local recurrence), a selective approach to imaging studies is warranted. For this patient population, we recommend complete blood count, liver function tests including alkaline phosphatase and LDH, a chest roentgenogram, and a CT scan of the abdomen. Although the yield of these tests, particularly CT of the abdomen, in detecting distant metastases in asymptomatic patients is low, they may identify false-positive abnormalities and provide an important baseline for future studies in this high-risk population. For patients with disease below the waist or in the head and neck region, we recommend CT of the pelvis and CT of the neck, respectively. Additional studies should be done only if clinically indicated. Finally, patients with known systemic disease (stage IV) should be more comprehensively evaluated, because the likelihood of detecting asymptomatic metastases is higher. Accordingly, in addition to the work-up outlined previously for stage III patients, we also perform a CT scan of the chest and MR imaging of the brain; other studies (e.g., bone scan, gastrointestinal series) are performed on the basis of symptoms.     

Current therapy for multiple myeloma

Multiple myeloma is an incurable plasma cell malignancy that accounts for 10% of all hematologic cancers. For decades the mainstay of therapy has been the use of melphalan and prednisone; with this regimen, the median survival is approximately 3 years. Recently, important advances were made that have substantially altered the manner in which patients with myeloma are treated. Newly diagnosed patients with good performance status are now treated with autologous stem cell transplantation, resulting in improved survival. Because of the increasing use of transplantation as initial therapy, several therapeutic issues have emerged: the role of tandem transplantation, early vs delayed transplantation, and the role of allogeneic transplantation. The pronounced activity of thalidomide in patients with refractory myeloma represents another important advance. This has prompted the study of several novel agents in the treatment of myeloma, at least 2 of which appear promising. Supportive care measures also have improved, including the use of bisphosphonates to prevent osteolytic lesions. The purpose of this review is to summarize recent advances and provide an evidence-based approach to the treatment of multiple myeloma.     

Bortezomib treatment for multiple myeloma

OBJECTIVE: To review the pharmacology, pharmacokinetics, and place of bortezomib in the therapy of multiple myeloma (MM).DATA SOURCES: A MEDLINE search was conducted (1985-May 2003). Meeting abstracts, bibliographies from identified articles, and the package insert were also used. Search terms were bortezomib, multiple myeloma, Velcade, PS-341, LDP-341, MLNM341, and proteasome inhibitor.STUDY SELECTION AND DATA EXTRACTION: All published information relevant to the clinical activity of bortezomib in MM was considered. All human clinical studies, with an emphasis on Phase II trials, were selected.DATA SYNTHESIS: Current therapy for MM yields significant, although temporary, responses. Bortezomib is a novel anticancer agent with significant activity in relapsed and refractory MM.CONCLUSIONS: Although the clinical trial data are incomplete, bortezomib offers a novel therapeutic modality for patients with MM who would otherwise have few options.     

Systemic virotherapy for multiple myeloma

Introduction: The multiple myeloma (MM) treatment scenario has changed considerably over the past few years. Several novel targeted therapies are currently under consideration including oncolytic virotherapy.

Areas covered: This review provides an analysis of the mechanisms of action of virotherapy, and summarizes the preclinical and clinical studies of systemic virotherapy developed for the treatment of MM. Different types of viruses have been identified, including: adenovirus, vaccinia virus, herpes simplex virus 1, myxoma virus, reovirus, measles virus, vesicular stomatitis virus and coxsackievirus A21.

Expert opinion: The above-mentioned viruses can do more than simply infect and kill malignant plasma cells alone or in combination with chemo and/or radiotherapy. In fact, some of them can also be used to purge myeloma cells from an autologous bone marrow (BM) transplant. Further investigations are required to better explore the best therapeutic combinations for MM and to also overcome antiviral response immunity that can limit the efficacy of this therapeutic strategy.     

Diagnosis and staging of multiple myeloma using serum-based laser-induced breakdown spectroscopy combined with machine learning methods

Diagnosis and staging of multiple myeloma (MM) have been achieved using serum-based laser-induced breakdown spectroscopy (LIBS) in combination with machine learning methods. 130 cases of serum samples collected from registered MM patients in different progressive stages and healthy controls were deposited onto standard quantitative filter papers and ablated with a Q-switched Nd:YAG laser. Emissions of Ca, Na, K, Mg, C, H, O, N and CN were selected for malignancy diagnosis and staging. Multivariate statistics and machine learning methods, including principal component analysis (PCA), k-nearest neighbor (kNN), support vector machine (SVM) and artificial neural network (ANN) classifiers, were used to build the discrimination models. The performances of the classifiers were optimized via 10-fold cross-validation and evaluated in terms of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curves (AUC). The kNN, SVM and ANN classifiers achieved comparable discrimination performances with accuracies of over 90% for both diagnosis and staging of MM. For diagnosis of MM, the classifiers achieved performances with AUC of ∼0.970, sensitivity of ∼0.930 and specificity of ∼0.910; for staging of MM, the corresponding values were AUC of ∼0.970, sensitivity of ∼0.910 and specificity of ∼0.930. These results show that the serum-based LIBS in combination with machine learning methods can serve as a fast, less invasive, cost-effective, and robust technique for diagnosis and staging of human malignancies.     

中性粒细胞/淋巴细胞比值对多发性骨髓瘤患者的预后评估价值

目的探讨外周血中性粒细胞/淋巴细胞比值(NLR)在多发性骨髓瘤(MM)患者预后中的价值。方法回顾性分析87例初诊MM患者和100例体检健康者临床资料,将MM患者以NLR平均值为临界值分为低NLR组(NLR<2.68)和高NLR组(NLR≥2.68),分析2组性别、年龄、国际分期体系(ISS)、总体生存期、实验室检查结果等资料的差异,通过Kaplan-Meier法和Cox比例风险回归模型做单因素和多因素分析,确定影响MM患者的预后因素。结果MM组的NLR值明显高于健康对照组(t=2.21,P<0.05)。与低NLR组比较,高NLR组血清β2-微球蛋白(β2-MG)、钙、肌酐水平偏高,差异有统计学意义(P<0.05)。高NLR组较低NLR组总体生存期短、5年生存率低。单因素分析和多因素分析结果显示,NLR≥2.68,β2-MG升高是MM预后不良的危险因素及独立危险因素(P<0.05)。结论NLR是MM患者预后判断的1个独立危险因素,高水平NLR患者的总体生存期短,但需大样本资料证实。     

The prognostic significance of cytological study of the bone marrow in multiple myeloma

AIM: To show that the activity of a multiple myeloma (MM) course, its sensitivity to chemotherapy and prognosis correlate with maturity of medullary plasma cells (MPC). MATERIAL AND METHODS: Bone marrow films from 88 primary MM patients. The films were stained by Romanovsky-Giemsa and studied by the immersion objective. Four types of MPC maturity by Ph. Greipp et al. classification were identified: mature (n = 5), intermediate (n = 55), immature (n = 26) and plasmoblastic type (n = 2). RESULTS: The survival median in MM patients with immature MPC type was 18 months, with intermediate type--46 months (p < 0.05). Anemia was registered in 73 and 51% of the patients, respectively (p < 0.05). The average amount of MPC was 51 and 30%, respectively (p < 0.05). The percentage of MPC does not always correlate with the tumor mass in MM. To make a more accurate MM diagnosis it is valid to make additional histological investigations of the bone marrow. With transition of the stable MM phase into the aggressive one bone marrow comprises more immature MPC and plasmoblasts. CONCLUSION: MM patients with immature and plasmoblastic type of MPC belong to the group of high risk and should receive combined and intensive polychemotherapy immediately after the diagnosis.     

Diagnosis and management guideline for multiple myeloma

The prognosis of patients with multiple myeloma has been improved in the last decade due to the induction of autologous stem cell transplantation and novel drugs including thalidomide, lenalidomide, and bortezomib into the treatment. Recently, the UK Myeloma Forum and International Myeloma Foundation have successively proposed myeloma management guidelines. Because many novel drugs are not available in Japanese patients, we can not use the same treatment strategy in U.S.A. and Europe. In this chapter, the diagnosis and management guideline is proposed for Japanese patients with myeloma. For convenience, the recommendations are divided into: 1. Diagnostic criteria 2. Indications for starting therapy 3. Treatment(initial therapy, maintenance therapy, and therapy for refractory/relapsed patients) 4. Response criteria 5. Supportive care and management of specific complications.     

校正血钙对多发性骨髓瘤患者Durine-Salmon分期及肾功能的影响

目的:比较多发性骨髓瘤(MM)患者血清钙校正前后对Durine-Salmon(DS)分期的影响,以及与血尿素氮(BUN)、血肌酐(Scr)的关系.方法:回顾性分析天津市第三中心医院2004年6月至2010年7月确诊的63例MM患者初次入院时的临床病例资料及实验室检查结果,并根据MM的Durine-Salmon(DS)分期系统分别以校正前、后血钙值为基础比较DS分期,以及血清钙与肾功能损害的关系.结果:血钙校正前后对DS分期差异有统计学意义.血钙校正前对BUN的影响在低钙组和高钙组间差异显著,对Scr的影响在高钙-低钙组以及高钙-正常组间存在明显区别(P<0.05);血钙校正后对血BUN、Scr的影响在高钙组和正常组之间差异具有统计学意义(P<0.05).结论:校正血钙对MM患者DS分期具有重要影响,并且与反映肾功能损伤的Scr、BUN有重要关系,从而对疾病的早期诊断和治疗具有重要的临床意义.     

硼替佐米为主的联合方案治疗多发性骨髓瘤的临床观察

目的观察硼替佐米为主的联合方案治疗多发性骨髓瘤的疗效和安全性。方法多发性骨髓瘤患者15例,其中初治患者9例,复发难治者6例,采用至少2个疗程的硼替佐米(1.3 mg/m2,第l、4、8、11天),同时联合沙利度胺(100～200 mg/d)及地塞米松(20～40 mg/d,第1～4、8～11天)治疗,21 d为1个疗程。疗效判断参照国际骨髓瘤工作组(IMWG)标准,化疗相关不良反应参照WHO标准分级。结果 9例初治患者达完全缓解CR 3例(33.3%),非常好的部分缓解VGPR 4例(44.4%),部分缓解PR 2例(22.2%),总有效率为100%;6例复发难治患者达CR 1例(16.7%),VGPR 1例(16.7%),PR 2例(33.3%),疾病稳定(SD)1例(16.7%),疾病进展(PD)1例(16.7%),总有效率为83.3%。常见不良反应包括血小板下降10例(66.7%),白细胞减少7例(46.7%),胃肠道反应8例(53.3%),周围神经病变6例(40%),严重带状疱疹1例(0.07%),低血压1例(0.07%),经治疗均可耐受。结论硼替佐米为主的联合方案治疗初治及复发难治多发性骨髓瘤患者具有有效率高、耐受性好等优点,为多发性骨髓瘤患者治疗提供了一种全新的治疗方法。