【作者】 关晶；

【导师】 付蓉； 邵宗鸿；

【作者基本信息】 天津医科大学 ， 内科学， 2008， 硕士

【摘要】 一.多发性骨髓瘤患者骨病发病及其相关因素研究目的探讨多发性骨髓瘤（MM）骨病发病及其相关因素。方法对1983年1月至2006年6月天津医科大学总医院血液肿瘤科确诊并住院治疗的统计84例MM患者进行回顾性病例总结及分析,了解MM骨病发病率及其临床和实验室特征,得出MM骨病发生的危险因素及保护因素。结果①MM骨病发生率83.3%;按骨病类型统计溶骨性病变发生率60.9%、病理性骨折为32.8%、骨质疏松80%、软组织肿物6%,前两组的发生率有统计学差异（P＜0.05）;按骨病发生部位统计,颅骨骨病发生率58%、肋骨骨病发病率42%,均高于四肢长骨（20.3%）（P＜0.05）;MM各期（Durie-Salmon分期）骨病的发生率分别为Ⅰ期0、Ⅱ期26%、Ⅲ期38%;MM各型骨病发生率分别为IgG型90.6%、IgA型86.7%、轻链型和未分泌型均为100%,各组骨病的发生率无统计学意义。②影响MM骨病发生的宿主因素:50岁以上（包括50岁）的MM患者是骨病发生的高危人群,骨病的发生率为89.4%,明显高于50岁以下的患者（66.7%）（P＜0.05）。性别与MM骨病的发生不相关。③影响MM骨病发生的肿瘤相关因素:MM骨病患者血清白蛋白平均为33.13±6.09g/L、不伴骨病者为39±4.38g/L,两组比较有统计学差异（P＜0.05）;伴有骨病的MM患者血清β₂-微球蛋白平均为8.11±5.64mg/L、不伴骨病者为0.95±0.34mg/L,两组比较有统计学差异（P＜0.05）:伴有骨病的MM患者血清球蛋白平均为53.40±28.39g/L、不伴骨病者为33.09±20.02g/L,两组比较有统计学差异（P＜0.05）:骨髓分类有不成熟浆细胞者骨病发生率96.1%、无不成熟浆细胞者为81.3%,两组比较有统计学差异（P＜0.05）;伴有骨病的IgG型MM患者血清IgG平均为6818.64±2822.57mg/dL、不伴骨病者为2425.5±1430.48mg/dL,两组比较有统计学差异（P＜0.05）;伴有骨病的MM患者血钙平均为4.86±3.19 mmol/L、不伴骨病者为1.93±0.37mmol/L,两组比较有统计学差异（P＜0.05）:伴有骨病的MM患者血尿酸平均为392.59±171.61umol/L、不伴骨病者为242.5±219.45umol/L,两组比较有统计学差异（P＜0.05）。比较伴/不伴骨病MM患者的血清C-反应蛋白、血磷、尿素氮、肌苷、骨髓浆细胞比例以及IgA型、轻链型的M蛋白水平,各组间比较均无统计学差异。④多因素分析:Logwastic回归方程显示,血清球蛋白和β₂-微球蛋白与MM骨病的发生相关,二者均是MM骨病发病的危险因素。结论①MM骨病发生率83.3%;按骨病类型统计溶骨性病变发生率60.9%、病理性骨折为32.8%、骨质疏松80%、软组织肿物6%,其中溶骨性病变的发生率高于病理性骨折组;按骨病发生部位统计,颅骨、肋骨骨病发病率均高于四肢长骨。②与MM骨病发生相关的单因素指标包括:年龄、血清白蛋白水平、血清β₂-微球蛋白水平、血清球蛋白水平、血钙、血尿酸、血清M蛋白水平（IgG型）、骨髓浆细胞类型。③与MM骨病发生相关的多因素指标包括:血清β₂-微球蛋白水平和血清球蛋白水平,二者均为危险因素。二.多发性骨髓瘤患者生存期及其相关因素研究目的探讨多发性骨髓瘤（MM）生存期及其相关因素。方法对自1983年1月至2007年9月天津医科大学总医院血液肿瘤科确诊并住院的107例MM患者进行回顾性病例总结及分析,了解MM患者的生存期及其相关因素,并比较不同的治疗干预对MM患者生存期的影响。结果1.MM患者中位生存期为32月。2.影响MM生存期的宿主因素50岁以下、50～70岁、70岁以上组的MM患者生存期分别29.77±5.69月、42.42±7.28月、16.14±3.40月,其中70岁以上组生存期高于50～70岁组（P＜0.05）。性别与MM生存期无显著相关。3.影响MM生存期的肿瘤相关因素（1）初诊时合并症:伴/不伴MM髓外侵犯的患者生存期分别为16.32±4.52月和32.28±2.96月,前者短于后者（P＜0.05）;伴有感染的MM患者生存期为29.57±2.83月,短于不伴感染组（P＜0.05）:伴/不伴骨病与MM患者生存期无显著相关。（2）血液检查:外周血血小板计数正常（≥100×10⁹/L）组MM患者生存期为34.00±3.21月,长于血小板低于正常（Plt＜100×10⁹/L）组（P＜0.05）;血清β2-微球蛋白水平是MM生存期的相关因素:将MM患者分为β₂-微球蛋白＞2.9mg/L和＜2.9mg/L两组,平均生存期分别为27.11±3.60月和45.27±5.08月,前者显著短于后者（P＜0.05）:血尿酸正常组MM患者生存期（35.33±3.51月）长于血尿酸高于正常组（20.36±3.45月）（P＜0.05）。（3）骨髓检查:骨髓浆细胞比例是MM患者生存期的相关因素:按照骨髓浆细胞比例,分为小于15%、15～30%、30～50%、大于50%四组,平均生存期分别为32.67±4.82月、34.94±4.23月、30.28±5.87月、14.73±3.03月,其中骨髓细胞分类浆细胞大于50%组MM患者生存期分别短于浆细胞小于15%组和浆细胞15～30%组（P＜0.05）,其余各组间生存期无显著性差异（P＞0.05）;骨髓浆细胞类型是MM生存期的影响因素:按照骨髓细胞分类中浆细胞形态,分为原始浆细胞、幼稚浆细胞、成熟浆细胞、混合类型浆细胞四组,每组平均生存期分别13.67±5.17月、9.50±3.09月、33.33±4.83月、32.45±3.61月,其中骨髓细胞分类浆细胞为幼稚阶段组生存期分别短于成熟浆细胞组和混合浆细胞组（P＜0.05）,其余各组间生存期无显著性差异（P＞0.05）。（4）治疗对于MM生存期的影响:化疗方案中含/不含M₂方案两组MM患者,平均生存期分别为31.54±2.97月和19.17±5.43月,前者长于后者（P＜0.05）;治疗后骨髓浆细胞比例＜5%（骨髓CR）的MM患者平均生存期为36.03±3.46月,高于治疗后骨髓未达CR者（22.85±4.81月）（P＜0.05）;经1疗程化疗骨髓达CR的MM患者生存期高于1疗程未达CR者,二者平均生存期分别为44.20±5.90月和25.74±3.24（P＜0.05）。（5）外周血白细胞计数、血红蛋白水平,血清白蛋白、球蛋白水平,血钙水平,血清C-反应蛋白水平,血清乳酸脱氢酶水平,血清尿素氮、肌苷水平,尿蛋白定性,尿潜血,尿本周蛋白定性,Durie-Salmon分期,经治疗骨髓CR后继续治疗的疗程数,骨髓CR后是否复发,均不是MM患者生存期的相关因素。4.多因素分析:将以上单因素带入Cox回归模型,结果显示外周血血小板计数、血清β₂-微球蛋白水平、骨髓细胞分类中浆细胞类型和治疗后是否达到骨髓CR是MM患者生存期的独立影响因素。结论1.MM患者中位生存期为32月。2.与MM患者生存期单因素相关的指标包括:年龄、初诊时是否合并髓外浸润及感染、外周血血小板计数、血清β₂-微球蛋白水平、血尿酸水平、骨髓细胞分类中浆细胞比例及类型、治疗方案中是否含有M₂方案、治疗后是否达到骨髓CR、是否1疗程即达骨髓CR。3.与MM生存期多因素相关的指标包括:外周血血小板计数、血清β₂-微球蛋白水平、骨髓细胞分类中浆细胞类型、治疗后是否达到骨髓CR。4.了解MM患者生存期的相关因素,有利于为MM患者选择针对性强、有预见性的治疗方案,并可根据病情的轻重程度,开展MM的分层治疗,从而提高MM患者的疗效,延长其生存期。更多还原

【Abstract】 ⅠThe incidence and correlation factors of osteopathia in the patients with multiple myelomaObjective To investigate the incidence and correlation factors of osteopathia in the patients with multiple myeloma（MM）.Methods Eighty-four MM patients were hospitalized in our department from January 1983 to June 2006 were analyzed retrospectively.Results（1）The overall incidence of osteopathia in MM patients was 83.3%; according to the type of osteopathia,the osteolytic lesion was 60.9%,the pathologic fracture was 32.8%,the osteoporoswas was 80%,the pwerenchyma mass was 6%, and there was statwastical difference between the first two groups（P＜0.05）; according to the position of the osteopathia,crinial bone was 58%,costal bone was 42%,both were more frequent than that of the long bone in extremities（20.3%） （P＜0.05）:According to Durie-Salmon staging,in order,they were 0%,26%and 38%in three stages;According to the type of M protein in serum,IgG group was 90.6%,IgA group was 86.7%,both light chain group and smoldering group were 100%,and there was no statwastical difference between any two groups;MM patients elder than 50 years were with high risk of suffering osteopathia（89.4%vs 66.7%）. No male or female predominance in osteopathia.（2）Tumor burden index associated with MM osteopathia.According to the incidence of osteopathia,The MM patients were divided in four groups.There were statisfical difference of some tumor burden index between the two groups,including serum albumin,β₂ microglobulin,serum globulin,IgG（only IgG group）,serum calcium,serum uric acid, plasma cell type.There were also some indexed with no statistical difference between the two group,including serum CRP,serum phosphonium,BUN,Crea,the proportion of plasma cell in bone marrow,the quantity of M protein in IgA and light chain group. （3）Multiplicity.Logistic regression equation suggests that the serum globulin and β₂ microglobulin level were correlated with the incidence of osteopathia,and both of them were risk factors of MM.Conclusion The incidence of osteopathia（83.3%）in MM patients was highly correlated with serumβ₂ microglobulin and globulin level.ⅡThe survival time and correlation factors of patients with multiple myelomaObjective To investigate the survival time and correlation factors of patients with multiple myeloma.Methods 107 MM patients were hospitalized in our department from January 1983 to September 2007 were analyzed retrospectively,Results 1.The average survival time of MM patients was 32 months.2.The host factors influencing the survival time of MM patients.According to the age,all patients can be divided into three groups--under 50 years,50-70 years and over 70 years.Respectively,the overall survival time of this three groups were 29.77±5.69 months,42.42±7.28 months and 16.14±3.40 months.Ther was statistical difference （P＜0.05）between the last two groups.3.The correlation factor related to the survival time of MM patients.（1）The complications at diagnoswas,The survival time of MM patients with or without extra-marrow infiltration were 16.32±4.52 months and 32.28±2.96 months respectively（P＜0.05）;and that in patients with infection was 29.57±2.83 months,shorter than that in patients without infection （P＜0.05）;There was no statistical difference between patients with and without osteopathwas.（2）Laboratory examination.The survival time of patients with normal platelet count（Plt≥100×10⁹/L）was 34.00±3.21 months,longer than the patients with abnormal platelet count（Pit＜100×10⁹/L）;the serumβ₂ microglobulin level was correlated with the survival time of MM patients.The patients could be divided into two groups according to theβ₂ microglobulin level above or below 2.9mg/L,the average survival time of the two groups were 27.11±3.60 months and 45.27±5.08 months respectively（P＜0.05）;The average survival time of patients with normal uric acid level（35.33±3.51 months）was longer than that of higher uric acid patients（20.36±3.45months）（P＜0.05）.（3）Bone marrow examination.The proportion of plasma cell in bone marrow was another correlation factor,here, patients were divided into four groups according to the percentage of plasma cell in bone marrow--＜15%,15%-30%,30%-50%and＞50%.Respectively,the average survival time of this four groups was 32.67±4.82 months,34.94±4.23 months, 30.28±5.87 months,14.73±3.03 months,and the survival time of the fourth group was significantly shorter than the first and the second group（P＜0.05）,however,there was no statistical difference between other groups（P＞0.05）;the type of plasma cell was also a correlation factor to survival time,which could be divided into another four groups—plasmablast,immature plasma cell,mature cell and mixed plasma cell. The average survival time of this four groups were13.67±5.17 months,9.50±3.09 months,33.33±4.83 months,32.46±3.61 months respectively.The average survival time of the second group was shorter than the third and the fourth group（P＜0.05）, there was no statistical difference between other groups（P＞0.05）.（4）The influence of treatment to survival time.In patients received chemotherapy with or without M₂ scheme,the average survival time were 31.54±2.97 months and 19.17±5.43 months （P＜0.05）respectively;the survival time of patients received complete remwassion （CR）after treatment（36.03±3.46 months）was longer than others without CR （22.85±4.81 months）（P＜0.05）;After one course chemotherapy,the survival time of the patients with CR（44.20±5.90 months）was longer than that of the patients without CR（25.74±3.24 months）（P＜0.05）.（5）White blood cell count,hemoglobin level, serum albumin,serum globulin,serum calcium,serum CRP,serum LDH,BUN,Crea, urine protein,urine occult blood,urine Bence Jones protein,Durie-Salmon stage,the number of chemotherapy courses after CR had no relationship with survival.4.Multiplicity.There were several independent prognostic factors had relationship with the survival time of MM patients,including platelet count,serumβ2 microglobulin level,the type of plasma cell in bone marrow and whether CR or not after treatment in Cox regression model.Conclusion 1.The overall survival time of MM patients was 32 months.2.The single factors related to the survival time were age,extra marrow infiltration and infection at diagnosis,platelet count,serumβ₂ microglobulin level,serum uric acid, the proportion and type of plasma cell in bone marrow,whether including M₂ scheme in chemotherapy or not,whether received CR after treatment and whether received CR after one course chemotherapy.3.The multiple factors related to the survival time of MM patients were platelet count,serumβ₂ microglobulin level,the proportion and type of plasma cell in bone marrow and whether received CR after treatment.4.To comprehend the correlation factors related to the survival time of MM patients was good for choosing effective and individualized treatment.Furthermore,according to different individual situations,hierarchy treatment can be displayed for getting better outcome and longer survival time.更多还原