硼替佐咪皮下注射治疗多发性骨髓瘤的临床观察与护理

[目的]探讨硼替佐咪皮下注射治疗多发性骨髓瘤(MM)的疗效、副反应及护理。[方法]10例在我院诊断为MM病人接受硼替佐咪皮下注射并联合地塞米松进行化疗,给药前后做好病人的心理护理,化疗过程中评估病人疗效,并密切观察病人的不良反应且给予相应的治疗及护理。[结果]10例病人中2例达完全缓解,6例达部分缓解,2例病情稳定。1级周围神经病变3例,11级为1例,未见111级以上的周围神经病变。所有病人给予相应的对症处理后均能按计划完成治疗。[结论]硼替佐咪皮下注射治疗MM用药简便,疗效可靠且降低了重症周围神经病变的发生率。     

硼替佐米联合地塞米松治疗多发性骨髓瘤的临床研究

本研究观察硼替佐米治疗多发性骨髓瘤的疗效及不良反应。7例初治患者均采用硼替佐米联合地塞米松治疗；另3例复发难治患者中2例采用硼替佐米联合地塞米松，1例同时加用米托蒽醌和沙利度胺治疗。结果显示，根据EMBT标准判定疗效，7例初治患者中1例完全缓解（CR），5例部分缓解（PR），1例轻微缓解（MR）；3例复发难治患者中2例部分缓解（PR），1例轻微缓解（MR）。总缓解率（CR＋PR）80％。3例患者在治疗过程中出现血小板减少，1例出现腹泻，1例足部麻木，经对症处理后均恢复。结论：硼替佐米治疗初发及复发难治多发性骨髓瘤均有较好的疗效，对治疗相关的副反应患者可耐受。     

硼替佐米治疗多发性骨髓瘤的护理

[目的]总结硼替佐米治疗多发性骨髓瘤的临床护理经验。[方法]对20例多发性骨髓瘤病人应用硼替佐米联合地塞米松方案进行治疗,做好心理护理、用药护理、药物不良反应的护理。[结果]20例病人有10例完全缓解,8例部分缓解,2例轻微反应。出现的不良反应主要有疲乏、胃肠道反应、周围神经病变、骨髓抑制、带状疱疹。[结论]硼替佐米治疗多发性骨髓瘤有较好的疗效,加强不良反应的护理能顺利完成治疗。     

硼替佐米治疗多发性骨髓瘤的应用进展

多发性骨髓瘤(MM)作为中老年常见的血液肿瘤之一,预后相对较差,常规化学疗法(化疗)疗效欠理想。硼替佐米作为一种新药,属于蛋白酶体抑制剂,通过全新的机制达到抗骨髓瘤的作用。国内外临床研究表明硼替佐米单药以及同常规化疗药物组成的联合化疗方案对初始治疗,以及复发难治的MM患者均有良好疗效。因此以硼替佐米为主的联合化疗方案已被美国国家综合癌症协作网推荐作为MM患者治疗的重要选择之一。现将硼替佐米在MM治疗上的进展作一综述。     

硼替佐米治疗多发性骨髓瘤的护理

多发性骨髓瘤（muitiple myeloma,MM）是浆细胞在骨髓中呈恶性克隆增生的疾病,迄今仍是一种难以治愈的疾病,常规化疗完全缓解率不足10％,中位生存期为3年左右。硼替佐米（商品名：万珂）是第一个进入临床应用的蛋白酶体抑制剂,     

硼替佐米治疗多发性骨髓瘤患者的临床护理

多发性骨髓瘤(MM)是骨髓浆细胞恶性克隆性增生为特点的血液系统常见的恶性肿瘤,好发年龄多见于中老年[1]。大多数患者在病程中接受过多种治疗方法,只能获得短暂缓解,而骨髓细胞又易产生耐药性。硼替佐米是新型的酶蛋白抑制剂,可逆性地抑制蛋白酶体的活性,阻断NF-κB等多条通路,     

硼替佐米治疗初发性多发性骨髓瘤的护理

多发性骨髓瘤(Multiple myeloma)是一种单克隆浆细胞异常增生所致的恶性肿瘤,占血液恶性肿瘤的10%左右。当前主要的治疗方法是化疗和干细胞移植,均难以治愈。硼替佐米(Bortezo mib,商品名万珂)是新型的蛋白酶体抑制剂,能特异性抑制哺乳动     

硼替佐米对多发性骨髓瘤患者CD4+T淋巴细胞的影响

目的本研究旨在研究硼替佐米对多发性骨髓瘤患者外周血CD4+T淋巴细胞的影响及其与带状疱疹发生之间的关系。方法收集18例多发性骨髓瘤患者应用硼替佐米方案治疗前后的外周血,检测其淋巴细胞计数及T淋巴细胞亚群。结果 18例患者中16例出现CD4+T淋巴细胞下降(88.8%)。CD4+T淋巴细胞治疗前中位数为655个/μl(202～1166个/μl),治疗后中位数为251个/μl(40～816个/μl),下降61.6%(P<0.01)。10例患者下降幅度超过50%。大多数患者(12/18,66.6%)CD4+T淋巴细胞在硼替佐米治疗后低于400个/μl,部分患者(5/18,27.7%)甚至低于200个/μl。18例患者中有2例出现带状疱疹病毒感染,发生率为11.1%。2例患者CD4+T淋巴细胞治疗后<400个/μl。结论硼替佐米治疗多发性骨髓瘤可导致暂时性CD4+T淋巴细胞下降,细胞免疫功能下降,可并发带状疱疹病毒感染。     

硼替佐米治疗多发性骨髓瘤的临床护理

目的总结对多发性骨髓瘤患者采用硼替佐米药物期间的临床护理措施及经验。方法对2009年7月-2011年4月9例多发性骨髓瘤患者接受硼替佐米联合地塞米松、沙利度胺等治疗过程出现的不良反应,包括消化道反应、骨髓抑制、低血压和周围神经感觉异常等,采取对症有效的护理方法,使治疗安全顺利进行。结果 9例患者完全缓解4例,部分缓解4例,轻微反应1例,用药过程中均未发生与护理相关的不良反应。结论应用硼替佐米时,要严密观察不良反应并及时予以对症处理,以保证治疗的顺利进行及效果。     

硼替佐米治疗多发性骨髓瘤10例

目的:观察硼替佐米治疗初治、复发难治多发性骨髓瘤的疗效及不良反应.方法:2007年3月至2008年10月宁波第一医院血液科住院的10例多发性骨髓瘤患者(7例初治,3例复发难治),其中7例初治1例复发难治接受VTD方案:硼替佐米1.0～1.3 mg/m2(d1,d4,d8,d11),地塞米松20～40mg/d(d1～4,d8～11),反应停100mg/d,复发难治者中另2例在此基础上分别加用环磷酰胺0.4mg/d(d1～4)(VTCD方案),或表阿霉素10mg(d1～4)(VTAD方案),21 d为1个周期.每例患者接受1～8疗程化疗.结果:随访1～20个月,10例患者中CR 2例,nCR 3例,PR 3例,MR 1例,NC 1例.总体缓解率(CR+nCR+PR)80%(8/10),总体有效率90%(9/10).10例患者中出现末梢神经炎5例(5/10),白细胞减少4例(4/10),血小板减少4例(4/10),继发感染6例(6/10),33例次化疗中出现白细胞减少6例次(18.1%),血小板减少6例次(18.1%),发生感染13例次(39.4%),其中1例死于感染.结论:硼替佐米治疗初治或复发难治的多发性骨髓瘤是一种可以耐受的、疗效确切的治疗新选择,并发症中感染发生率高,末梢神经炎较多见.     

The genetic variability of MDR1 C3435T polymorphisms in four Southern Chinese populations

Objectives

To investigate the genetic variability of multiple drug resistant 1 (MDR1) gene C3435T polymorphism in four Southern Chinese populations.

Methods

Using discrimination real-time PCR, we determined the MDR1 C3435T polymorphism in three ethnic minority groups Lahu (n = 104), Wa (n = 101) and Bulang (n = 100) in Yunnan Province, and Han Chinese (n = 199) in Hong Kong. All of them were residents in Southern China.

Results

For 3435 CC genotype, the frequency in Han Chinese in Hong Kong (44.7%) is significantly higher than in Lahu (16.3%) and Wa (29.7%) minorities, P < 0.05. For 3435 CT genotype, the frequency in Han Chinese in Hong Kong (44.2%) is lower than in Lahu (58.7%), P < 0.05. For 3435 TT genotype, frequency in Han Chinese in Hong Kong (11.1%) is lower than in Lahu (25%) and Wa (20.8%), P < 0.05. For 3435 C allele, frequency in Han Chinese in Hong Kong (66.8%) is higher than in Lahu (45.7%) and Wa (54.5%), P < 0.01. For 3435T allele, frequency in Han Chinese in Hong Kong (33.2%) is lower than in Lahu (54.3%) and Wa (45.5%), P < 0.01. For MDR1 3435T allele, the frequencies are significantly higher in our four Southern Chinese populations than in African population (P < 0.001) and significantly lower than in South-west Asians (P < 0.05); Han Chinese in Hong Kong displayed significant difference from all the other ethnic populations except Japanese (P < 0.05); compared with Caucasian and other ethnic Asians, Lahu minority showed no frequency difference (P > 0.05) between Caucasian and other Asians (except Japanese).

Conclusions

This is the first study to show the C3435T polymorphism of MDR1 in Southern Chinese populations. The frequency of C3435T, an important determinant for multidrug resistance, displays significant difference in ethnics. It may help for individualizing therapy for cancer, HIV and other common diseases.     

硼替佐米联合地塞米松治疗16例复发、难治性多发性骨髓瘤患者

目的 观察硼替佐米联合地塞米松治疗复发、难治性多发性骨髓瘤（MM）患者的疗效和不良反应。方法16例复发、难治性MM患者，男性9例，女性7例，平均年龄57．5（40～77）岁。在为期3周的疗程内给予硼替佐米3．5mg静脉注射，第1，8天或1．3mg／m^2，第1，4，8和11天。每次使用硼替佐米之前给予地塞米松30～40mg静脉注射。每例患者接受1～4个疗程的治疗。采用EBMT标准观察疗效，并按NCICTCAE（第3版）标准判断不良反应。结果 中位随访6个月，14例（87．5％）患者对治疗有效，其中7例患者接近完全缓解，5例部分缓解，2例轻微反应，2例无变化。最常见的不良反应为胃肠道症状，存16例患者中，12例患者有不同程度的恶心或呕吐，3例出现便秘，3例发生严重腹泻，有8例血小板减少，另有3例乏力等，经对症治疗后均获缓解。结论 硼替佐米联合地塞米松是一种对复发、难治性MM的新的治疗选择，不良反应少。     

Detection of C1236T,G2677T/A,and C3435T polymorphism of MDR1 by amplification refractory mutation system PCR

C1236T, G2677T/A, and C3435T polymorphism of the multidrug resistance (MDR1) gene have substantial impact on expression or activity of P‐glycoprotein (P‐gp). We developed new methods based on amplification refractory mutation system (ARMS) to detect these polymorphisms. Tetra‐primers amplification in a single tube was established to detect C1236T and C3435T polymorphism. For G2677T/A polymorphism, a two‐step allele‐specific amplification method was used. MDR1 genotypes of 177 Chinese subjects were determined by the methods we established. The methods we established were verified with gene sequencing. Gene frequencies of 1236C and 1236T were 37.8 and 62.2%, respectively; gene frequencies of 2677G, 2677T and 2677A were 44.1, 38.4 and 17.5%, respectively; the gene frequencies of 3435C and 3435T were 65.0 and 35.0%, respectively. The results were similar with other studies on Oriental subjects. The methods we established are simple, accurate, and economical, and can provide reliable approaches for determining MDR1 polymorphism. J. Clin. Lab. Anal. 23:110–116, 2009. © 2009 Wiley‐Liss, Inc.     

The single nucleotide polymorphism and haplotype analysis of MDR1 in Chinese diffuse large B cell lymphoma patients

We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide polymorphism (SNP) and haplotype variants were associated with the susceptibility to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study. They were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing at three common loci: C1236T, G2677T/A and C3435T. At locus G2677T/A, allele G and genotype GT were significantly more common in DLBCL (G: OR = 1.48, 95% CI: 1.08–2.02, Pc = 0.03; GT: OR = 1.96, 95% CI: 1.25–3.07, Pc < 0.01), while genotype AT in this locus seemed to be protective (OR = 0.29, 95% CI: 0.02–0.72, Pc = 0.03). TT genotype at locus C3435T showed a risk factor in DLBCL (OR = 2.38, 95% CI: 1.52–3.74, Pc < 0.01). The frequency of T-G-T haplotype was significantly increased in DLBCL group (OR = 5.21, 95% CI: 2.58–10.54, Pc < 0.01); haplotype of G-T in 2677–3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group (G-T: OR = 3.97, 95% CI: 2.31–6.85, Pc < 0.01; 2677GT/3435TT: OR = 4.55, 95% CI: 2.02–10.22, Pc < 0.01). Our findings demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677–3435 and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective genotype. These findings could provide evidence that the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.     

The single nucleotide polymorphism and haplotype analysis of MDR1 in Jiangsu Han population of China

The aim of this study was to perform the frequency distribution of MDR1 gene SNPs and haplotypes of Jiangsu Han population in China. A total of 225 Jiangsu Han unrelated volunteers were enrolled and genotyped by PCR-ASP method at three loci: C1236 T (rs1128503), G2677 T/A (rs2032582) and C3435 T (rs1045642). In total, C and T were found at locus 1236, with the frequency of 35% and 65%, respectively. The most frequent allele at locus 2677 was G with the frequency of 44%, followed by T (41%) and A (15%). At locus 3435, C was more common (60%) than T (40%). The most common haplotype at loci 1236-2677-3435 was T-T-T (31.84%), at loci 1236-2677 was T-T (37.68%), at loci 2677-3435 was G-C (39.06%), and at loci 1236-3435 was T-T (34.28%). The haplotype linkage disequilibrium study found that all three loci were in linkage disequilibrium, such as T-T at loci 1236-2677, T-T at loci 2677-3435 and C-C at loci 1236-3435 (P < 0.01). The dendrogram study indicated that the distribution of MDR1 SNPs in Jiangsu Han population were close to Japan and Malay populations and far away from European countries. These findings could shade new lights in population genetics and anthropology studies of Han-Chinese. It also provides basic data for research on MDR1 gene polymorphism, disease association and drug resistance study.     

多药耐药基因C3435T与G2677T/A单核苷酸多态性检测方法的探讨

目的 建立简便、快速检测多药耐药基因(MDR1)C3435T与G2677T/A单核苷酸多态性(SNPs)的方法 .方法 针对MDR1 C3435T分别设计相对的两对引物-聚合酶链反应(PCR-CTPP)、序列特异性聚合酶链反应(PCR-SSP)及DNA测序方法 的引物,针对MDR1 G2677T/A分别设计PCR-SSP和DNA测序方法 的引物,优化PCR反应条件.将PCR-CTPP和PCR-SSP方法 的基因分型结果 与DNA测序结果 进行比对,确定准确性.在优化条件下,分别对50例健康体检者的外周血白细胞DNA进行MDR1 C3435T和C2677T/A基因型分析.结果 通过条件优化,PCR-CIPP、PCR-SSP方法 可快速的清晰区分MDR1 C3435T与G2677T/A的基因型,结果 与DNA测序方法 相符合.50例健康体检个体MDR1 C3435T与G2677T/A的基因型分布均符合Hardy-Weinberg平衡(P0.05).MDR1 C3435T PCR-CTPP结合G2677T/A PCR-SSP的检测方法 为最佳选择.结论PCR-CTPP、PCR-SSP方法 可简单、准确、经济、快速地检测MDR1 C3435T、G2677T/A SNPs,具有临床应用价值.     

硼替佐米联合化疗与常规化疗方案治疗多发性骨髓瘤的临床比较

目的 观察硼替佐米联合地塞米松及沙利度胺BDT(Velcade+ Daxamethasone+ Thalidomide)方案与改良VAD(Vinorebine+Pirarubicin+Daxamethasone)方案、MPT(Melphalan+ Prednisone+ Thalidomide)治疗初发或复发/难治性多发性骨髓瘤患者的疗效及不良反应.方法 52例多发性骨髓瘤(MM)患者均为Durie-Salmon分期Ⅲ期,其中初治45例,复发/难治7例.21例(16例初治,5例复发/难治)MM患者采用BDT方案治疗,19例(18例初治,1例复发/难治)MM患者采用改良VAD方案治疗,12例(11例初治,1例复发/难治)MM患者采用MPT方案治疗.临床疗效根据EBMT/IBMTR/ABMTR标准判定,不良反应按依据NCICTCAE标准判断.结果 BDT方案组患者骨痛症状明显消失,贫血及肾功能不全得到明显改善,甚至恢复正常,21例患者中14例(66.7%)完全缓解(CR),6例(28.6%)部分缓解(PR),1例(4.8%)无变化(NC),总有效率为95.2%;改良VAD方案组19例患者中5例(26.3%)CR,3例(15.8%)PR,5例(26.3%)微小缓解(MR),2例(10.5%)NC,4例(21.0%)疾病进展(PD),总有效率为68.4%;MPT方案组12例患者中1例(8.3%)CR,2例(16.7%)PR,2例(16.7%)MR,1例(8.3%)NC,6例(50.0%)PD,总有效率为50.0%;三组间疗效比较差异有统计学意义(P<0.05).出现的不良反应包括血液学毒性和非血液学毒性.BDT组所有不良反应均在对症处理或停药后缓解或减轻.结论硼替佐米联合地塞米松及沙利度胺是一种新的有效治疗多发性骨髓瘤的化疗方案,不良反应轻且大多可逆,患者具有较好的耐受性.     

Rapid detection of the UGT1A1 single nucleotide polymorphism G211A using real-time PCR with Taqman minor groove binder probes

The UGT1A1 Taqman MGB probe single nucleotide polymorphism (SNP) genotyping assay was developed to detect nucleotide 211 of the UDP-glucoronocyltransferase 1A1 (UGT1A1) gene. Defects in this enzyme interfere with process of conjugation of bilirubin and cause unconjugated hyperbilirubinemia. Variation at nucleotide 211 in the coding region of the UGT1A1 gene has been shown to be prevalent in Japanese and Chinese. Using an ABI sequence detection system (SDS) 7000, an allele-specific real-time PCR-based genotyping method was established to detect nucleotide G211A. Cord blood from 125 infants without hyperbilirubinemia (controls) were compared with cord blood from 74 infants (cases) with severe hyperbilirubinemia (total serum bilirubin > 300 micromol/L). Homozygous variation of the UGT1A1 gene at nucleotide 211(A/A) is significantly more common in cases (14.9%) than in controls (0.8%) (P<0.001). Direct sequencing from 20 randomly selected samples showed eight samples with homozygous wild type, seven with homozygous variant, and five samples were heterozygous. The result from this assay was in complete concordance with the DNA sequencing result and clearly discriminate wild-type (G/G), homozygous variant (A/A), and heterozygous (G/A). This assay is rapid and robust for screening of SNP G211A to determine if this polymorphism plays a role in causing severe neonatal jaundice in the local context.