多发性骨髓瘤治疗后血清游离轻链比值正常化对预后的影响

本研究旨在探讨多发性骨髓瘤治疗后血清游离轻链比值（sFLCR）正常化及其对预后的影响。回顾性分析2009年1月至2013年12月我院42例多发性骨髓瘤患者的临床资料,将多发性骨髓瘤患者治疗后获得最好疗效时sFLCR持续正常超过4周的患者归为正常化轻链比患者,反之为异常轻链比患者;分析其传统预后因素对sFLCR的影响及sFLCR对患者总生存期（OS）的意义。结果表明,多发性骨髓瘤患者的年龄、ISS分期在正常化sFLCR组及异常sFLCR组之间存在统计学差异,上述两种指标对治疗后骨髓瘤sFLCR均有负性影响（P〈0.05）;sFLCR达到正常化血轻链比值患者具有相对较好的总生存期（P〈0.01）。结论：治疗后sFLCR正常化能够初步提示多发性骨髓瘤的预后较好。     

20例初诊多发性骨髓瘤血清游离轻链测定及其临床意义

本研究测定多发性骨髓瘤（multiple myeloma，MM）患者血清游离轻链（serum free light chain，sFLC）数值，并与血清总轻链（游离＋结合）比较，探讨sFLC测定在MM患者中的临床意义。应用免疫比浊法测定20例初治MM患者及20例正常对照人群sFLC数值，同期测定患者血清总轻链数值，计算sFLC及血轻链结果的K／h比率，其中18例行免疫固定电泳（immunofixation electrophoresis，IFE）检查。结果表明：20例多发性骨髓瘤患者sFLC数值及K／h比值较正常人群均明显异常（P〈0．01），其敏感性明显高于血清轻链（P〈0．01）。结论：应用免疫比浊法测定sFLC并结合K／h比率在MM诊断中有重要的价值，sFLC检测可作为MM诊断的重要指标之一。     

血清总轻链与游离轻链定量检测在多发性骨髓瘤诊断中的临床价值探讨

目的 探讨血清总轻链（serum total light chain,sTLC）与游离轻链(serum free light chain,sFLC) 在多发性骨髓瘤(multiple myeloma, MM) 临床诊断中的应用价值。方法 选取空军军医大学第一附属医院2019 年10 月~2020 年1月期间收治的多发性骨髓瘤患者67 例,采集所选取患者的血清样本,检测sTLC 和sFLC 浓度,进行相应的统计分析。结果 67 例多发性骨髓瘤患者sTLC 和sFLC 检测结果的总符合率为56.72%。在MM诊断中,sFLC 异常检出率（92.54%）高于sTLC（70.15%）,差异具有统计学意义（χ2=11.064,P<0.01）。然而,联合检测sTLC 和sFLC 的异常检出率（94.03%）与sFLC 检测（92.54%）比较,差异无统计学意义（P=1.000）。结论 多发性骨髓瘤患者sTLC 与sFLC 检测结果的符合率较低,sTLC 在MM 的诊断中临床价值有限,sFLC 检测可为MM 的早期诊断提供可靠的实验室依据。     

血清游离轻链在多发性骨髓瘤中的临床意义研究

多发性骨髓瘤患者(MM)因浆细胞克隆性增生致血清中产生大量单克隆游离轻链。血清游离轻链(serumfree light chain,sFLC)检测在浆细胞疾病(plasma cell dyscrasias,PCD)的应用中日益突出。免疫比浊法检测sFLC是一种敏感度高、特异性强的快速自动、定量的检测手段。本研究探讨多发性骨髓瘤中sFLC水平并分析多发性骨髓瘤中sFLC与血清总轻链(sTLC)相关性。应用免疫散射比浊法测定明确诊断的45例多发性骨髓瘤初诊患者的血清游离κ及游离λ浓度,计算游离κ及游离λ的比值,评价sFLC在多发性骨髓瘤患者中的临床意义。结果表明,MM患者的sFLC及其比值与正常人具有明显统计学差异(tκ=13.53,P<0.001;tλ=17.53,P<0.001;tκ/λ=4.26,P<0.001);MM患者的sFLC和sTLC及二者的比值间无明显相关性。结论:MM患者中sFLC水平明显高于正常人,sFLC及其比值可作为MM的诊断指标之一。sTLC的测定不能代替sFLC。     

游离轻链检测对多发性骨髓瘤诊断的临床意义

目的评价免疫固定电泳、尿液轻链定量及血清游离轻链检测在多发性骨髓瘤（MM）患者轻链检测中的价值。方法用速率散射比浊法进行重链、轻链及游离轻链定量,用蛋白电泳及免疫固定电泳法对M成份做定性分析,对多发性骨髓瘤患者轻链型21例,完整型29例（其中IgGI、gA型19例;IgD型10例）标本分别做免疫固定电泳,尿轻链定量及游离轻链检测,然后比较三种方法的检出率和灵敏度。结果对于轻链型骨髓瘤患者,免疫固定电泳、尿轻链定量及血清游离轻链检测三种方法的轻链检测阳性率分别为90.5%（19/21）;80.9%（17/21）;100%（21/21）。对于完整型骨髓瘤患者三种方法的游离轻链检测（免疫固定电泳法检测与重链结合的单克隆轻链的阳性率100%）阳性率分别为20.7%（6/29）;41.4%（12/29）;82.7%（24/29）。结论血清游离轻链检测较另外两种方法检测游离轻链更为灵敏,其与免疫固定电泳法结合检测对多发性骨髓瘤患者的明确诊断、疗效观察及改善预后起重要作用。     

血清游离轻链检测在轻链型多发性骨髓瘤诊治中的应用

多发性骨髓瘤（Multiple meyeloma,MM）是常见的恶性血液系统疾病,按免疫学分类可分为IgG、IgA、IgD、IgM、轻链型等多种类型。血清游离轻链（serumfree light chain,sFLC）的测定对于MM的诊断、疗效评价、预后判断等方面具有重要意义。     

血清游离轻链测定中应考虑的问题

尿中游离轻链(free light chains,FLC)测定及临床意义评估已有大量文献报告。最近,测定血清FLC的试剂已商品化,对单克隆γ球蛋白增多症(monoclonal gammopathies,MGP)的检测敏感性可达88％～98％,显著高于传统的电泳和免疫固定技术(检出率76％～79％),故被视为MGP的标志物。定量测定血清FLC可测出2／3的非分泌性骨髓瘤     

血清κ/λ轻链比值及蛋白电泳在诊断多发性骨髓瘤中的临床应用

目的 探讨多发性骨髓瘤(MM)患者血清轻链(sLC)κ/λ比值及血清蛋白电泳(SPE)在MM诊断中的临床价值.方法 采用速率散射免疫比浊法测定282例MM患者及521例健康对照人群sLC水平并计算κ/λ比值,同时做SPE和免疫固定电泳(IFE).以临床已确诊为MM的患者分型结果为标准,评价sLC比值联合SPE检测对MM...     

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。     

IgG合并游离KAP轻链型双克隆型多发性骨髓瘤实验室特点及临床特征

目的探讨IgG合并游离KAP轻链型双克隆性多发性骨髓瘤的实验室特点及临床特征。方法报道1例IgG合并游离KAP轻链型双克降性多发性骨髓瘤的实验室检查特点及临床的特征并复习相关文献。结果患者入院时血清IgG和游离KAP轻链型蛋白明显增高,血清免疫电泳示γ区出现双M峰,尿本周蛋白强阳性,免疫固定电泳抗IgG和抗KAP形成2条异常固定带。X线和MRI示多处溶骨性损害和腰椎的压缩性骨折。骨髓涂片示浆细胞27.5%,有异常浆细胞浸润。给予4疗程DVD-T方案化疗,化疗后患者临床症状完全缓解,血清IgG蛋白恢复正常,游离KAP蛋白下降,骨髓缓解。结论 IgG合并游离KAP轻链型双克隆性多发性骨髓瘤非常罕见,其诊断尚未明确标准,目前国内外尚未见报道,需更多病例资料以总结其临床特征及预后。     

多发性骨髓瘤患者血清sFLC、LDH及β2-MG水平及其与预后的关系

目的探讨多发性骨髓瘤(MM)患者血清游离轻链(sFLC)、乳酸脱氢酶(LDH)、β2-微球蛋白(β2-MG)水平及其与预后的关系。方法选取2014年1月至2019年2月四川省第五人民医院收治的94例MM患者及100例体检健康者,测定受试者血清sFLC、LDH及β2-MG水平,随访记录MM患者总生存时间。结果κ-MM组患者sFLC-κ水平及sFLC-κ/sFLC-λ(sFLC-κ/λ)比率显著高于健康对照组(P<0.05);λ-MM组患者sFLC-κ、sFLC-λ水平明显高于健康对照组,sFLC-κ/λ比率低于健康对照组(P<0.05);MM组患者血清LDH及β2-MG水平均显著高于健康对照组(P<0.05)。入组94例患者均获得随访,Kaplan-Meier生存曲线分析显示国际分期系统(ISS)分期、轻链比率、LDH水平与患者总生存时间相关(P<0.05)。Cox多因素分析显示,校正ISS分期等因素后,轻链高比率(sFLC-κ/λ≥100.00或≤0.01)及LDH≥225 U/L是MM患者预后不良的独立危险因素(P<0.05)。结论MM患者存在血清sFLC-κ、sFLC-λ表达异常及LDH、β2-MG水平升高。sFLC-κ/λ比率及LDH水平与MM患者预后相关,可作为判断患者预后的指标。     

31例轻链型多发性骨髓瘤实验室指标分析

目的探讨实验室检测指标在轻链型多发性骨髓瘤(MM)诊治中的应用价值。方法收集轻链型MM患者31例及对照组60例,对照组为健康者20例(健康组),以及该院诊断的IgGκ型和IgAκ型MM患者各20例。检测免疫球蛋白、血清蛋白电泳、免疫固定电泳、尿素氮(UREA)、肌酐(Cr)、β_2微球蛋白,并进行流式细胞免疫表型检测及骨髓细胞学检查。结果血清蛋白电泳检测到M蛋白的阳性率为29.03%,Durie-Salmon临床分期Ⅱ期与Ⅲ期M蛋白水平差异有统计学意义(P0.05);免疫固定电泳结果均需用琼脂糖凝胶电泳法加做IgD及IgE抗体复查;轻链型MM患者与健康者的IgG、IgA、IgM、UREA、Cr、β_2微球蛋白比较,差异有统计学意义(P0.05);MM细胞形态特征改变显著,细胞抗原表达以CD38、CD138、CD56为主。结论免疫球蛋白定量及免疫固定电泳可作为M蛋白的筛查方法,血清蛋白电泳可用于患者的临床分期和疗效观察;骨髓细胞学检查对轻链型MM起到重要的诊断作用,轻链型MM比其他类型MM有更加严重的肾功能损伤。     

Giant plasma cells with multiple immature nuclei in a young woman with newly diagnosed multiple myeloma

BackgroundMultiple myeloma with giant multinucleated plasma cells is a very rare entity and mostly reported cases are dated. This plasma cell morphology has been observed after monoclonal antibody treatments, such as daratumumab, and patients have experienced a worse prognosis with partial responses and a high rate of relapse.ResultsHere, we showed a newly diagnosed multiple myeloma with giant plasma cells with multiple (up to 13) immature nuclei who achieved a complete remission after a first line therapy and underwent to autologous hematopoietic stem cell transplantation, as per international guidelines.     

Urinary free light chain analysis by the Freelite immunoassay: a preliminary study in multiple myeloma

Evaluate the Freelite free light chain immunoassay for urine analysis in myeloma.Urine specimens from 20 patients were analyzed by Freelite (The Binding Site) and SDS-agarose gel electrophoresis (Hydragel protéinurie, Sebia).Using the kappa/lambda ratio, Freelite was more sensitive than electrophoresis to detect free light chains, but concentration was overestimated in 75% of cases.Despite high sensitivity and full automation, Freelite inaccurately measures monoclonal free light chains in urine.     

Rapid reduction of extremely high kappa free light chains in a patient with myeloma cast nephropathy

This report describes a patient with light chain myeloma and acute renal injury. Serum kappa free light chain (FLC) was extremely elevated, >33,000 mg/dL. Treatment with therapeutic plasma exchange (TPE) started day 2 for biopsy‐confirmed cast nephropathy. Bortezomib‐containing chemotherapy was initiated on day 5, and hemodialysis for tumor lysis syndrome on day 7. TPE alone decreased kappa FLC >70% by day 5, indicating direct FLC removal was successful in this patient. A total of 25 TPE procedures were performed in a 31‐day hospitalization. Hemodialysis was discontinued after 3 months, and the patient's renal function and kappa FLC remain stable. Although the use of TPE for FLC removal is controversial, recent evidence supports its use as adjuvant therapy for acute renal injury secondary to myeloma cast nephropathy. TPE can be effective for rapidly reducing FLC; however, several TPE procedures might be required to reduce the risk of hemodialysis dependency.     

初治多发性骨髓瘤患者治疗方案选择及疗效的预后意义研究

目的 探讨年龄<65岁[适合接受自体造血干细胞移植(ASCT)治疗]的多发性骨髓瘤(MM)患者治疗方案选择及其疗效反应的预后意义.方法 回顾性分析2005年6月至2009年12月收治的年龄<65岁的初发MM患者71例,其中一线接受ASCT治疗者21例(ASCT组),非移植组50例[接受常规化疔者30例(常规化疗组),接受硼替佐米为主新药方案治疗者20例(硼替佐米组)].根据各组患者治疗结果,分析治疗方案选择和疗效、疾病进展及生存率之间关系.结果 71例患者中位随访时间18(1～58)个月,预期3年总生存(OS)率为(79.8±6.3)%,无进展生存(PFS)率(54.8±9.0)%.诱导治疗后34例获得完全缓解(CR)或良好部分缓解(VGPR),硼替佐米组CR+VGPR率为80%(20例中有16例),明显高于常规化疗组的33.3%(30例中有10例)和ASCT组的38.1%(21例中有8例)(P<0.01).ASCT组移植后16例(76.1%)获得CR或VGPR,明显高于常规化疗组(P<0.01).常规化疗组、硼替佐米治疗组和ASCT组预期3年PFS率分别为(26.3±13.8)%(中位PFS期为21个月)、(40.5±20.1)%(中位PFS期为25个月)和(93.8±6.1)%(未达中位PFS期)(P=0.025).单因素分析发现诱导治疗获CR或VGPR(P=0.020)、最大疗效达CR及VGPR(P<0.01)、ASCT(P=0.002)和获最大疗效后维持治疗(P=0.0005)与患者PFS密切相关.诱导治疗方案和维持治疗与PFS无显著相关性.多因素分析提示仅ASCT治疗(P=0.039)和最大疗效达CR及VGPR(P=0.009)为PFS独立预后影响因素.常规化疗组、硼替佐米组和ASCT组3年预期OS率分别为(62.4±13.7)%、(94.1±5.7)%和(87.9±8.3)%,均未达中位值,差异无统计学意义(P=0.120).单因素分析提示诱导治疗获CR及VGPR(P=0.009)、最大疗效达CR及VGPR(P<0.01)、维持治疗(P=0.035)及获最大疗效后维持治疗(P=0.031)与0S相关,多因素分析提示仅最大疗效达CR及VGPR是OS独立预后影响冈素(P=0.005).结论 <65岁的初治MM患者最大疗效达CR及VGPR是OS和PFS独立预后影响因素,ASCT是PFS独立预后影响因素.硼替佐米为主的新药诱导治疗可迅速取得最佳疗效反应,ASCT后巩固治疗可提高患者最大疗效反应,并且获CR及VGPR后进行维持治疗具有更重要的意义.

Abstract：

Objective To explore the effect of treatment option on the response and outecomes in multiple myeloma ( MM) patients suitable for autologous hematopoietic stem cell transplantation ( autoHSCT). Methods A total of 71 newly-diagnosed MM patients less than 65 years admitted to Ruijin Hospital from June 2005 to December 2009 were analyzed retrospectively. Among them, 21 receieved auto-HSCT (HSCT group) with standard conditioning of melphalan 200 mg/m2, 30 received conventional chemotherapy (conventional group) and 20 received Bortezomib-based therapy (Bortezomib group). The responses and outcomes of different treatments were analyzed. Results The median follow-up duration for all patients was 18 (1 -58) months with estimated 3-year overall survival (3-yr OS ) of (79. 8 ± 6.3 ) % and progression-free survival (3-yr PFS) of (54.8 ±9.0)%. Thirty-four patients achieved complete remission (CR) or very good partial remission (VGPR) on induction therapy, which were 80% for the Bortezomib group, 33.3% for the conventional group and 38. 3% for the HSCT group. After auto-HSCT the CR + VGPR rate was increased to 76.1 % for the HSCT group. Overall, the 3-yr PFS was (26. 3 ± 13. 8) % ( median 21 months), (40. 5 ±20.1)% (median 25 months) and (93. 8 ± 6. 1)% ( median not reached, P = 0. 025 ) for conventional,Bortezomib and HSCT groups respectively. Univariate analysis demonstrated that CR/VGPR after induction ( P = 0.020), best response of CR/VGPR (P < 0.01), autoHSCT (P = 0.002) and maitenance therapy after CR/VGPR (P =0.0005) were associated with improved PFS and that CR/VGPR after induction (P =0.009), best response with CR/VGPR (P < 0.01), maintenance therapy for any patients (P = 0.035) and maintenance therapy for patients with CR/VGPR (P =0.031 ) were associated with OS. In multivariate analysis, only auto-HSCT (P =0.039) and best response of CR/VGPR (P =0.009) were independent prognostic factors for PFS and the best response of CR/VGPR was the only independent prognostic factor for OS (P =0.005). The estimated 3-yr OS was (62.4 ± 13. 7) % , ( 94. 1 ± 5. 7) % and (87. 9 ± 8. 3) % respectively for 3 groups. Conclusions For newly-diagnosed MM younger than 65 are suitable for auto-HSCT, the best response of CR/VGPR was associated with OS and PFS. Auto-HSCT is also important prognostic factor for PFS. Induction therapy with Bortezomib can achieve rapid CR/VGPR while auto-HSCT as a crucial consolidation therapy and maintenance therapy maybe also important for improvement of long-term outcome.