【作者】 周小英；

【导师】 张荣艳；

【作者基本信息】 南昌大学 ， 内科学， 2011， 硕士

【摘要】 目的：骨髓增生异常综合症(MDS)是一组异质性克隆性造血干细胞疾病,不同患者预后差异较大,通过对原发性MDS的好发人群、血常规、血清铁蛋白(SF)、血乳酸脱氢酶(LDH)、血β2-微球蛋白(β2-MG)、骨髓细胞形态学分析、细胞遗传学等特点,探讨原发性MDS的预后因素及对IPSS、WPSS、MDACC预后积分系统进行比较。有助于指导临床医师有效的判断疾病的预后,合理选择治疗方案。方法：回顾性分析南昌大学第一附属医院血液科2004年1月～2010年12月收治的212例诊断为原发性MDS的病例,其中98例获得随访资料。按WHO分型标准把原发性MDS进行分型,归纳总结其主要临床表现、血常规、生化指标、骨髓细胞形态学分析、骨髓活检、骨髓染色体及治疗方案的选择等特点及并进行生存期的比较,因为发生转急性白血病的病例数较少,因而不再进行预后因素与转白关系的进一步分析,根据生存期(OS)对IPSS、WPSS、MDACC预后积分系统行比较。所有数据采用SPSS16.0统计软件统计分析,计量资料以均数±标准差(x±s)表示,三个及以上的样本均数比较采用方差分析法,对有统计意义的,再用LSD法行两两比较；多样本非正态分布资料采用秩和检验；计数资料采用卡方检验,统计分析的显著性水准均选a=0.05,P<0.05为差异有统计学意义,生存率的估计采用Kaplan-Meier法,生存率比较采用Log-Rank检查。结果：(1)本组212例原发性MDS患者中,≥60岁73例,<60岁139例,中位发病年龄49(14-86)岁,患病率呈逐年上升趋势。随访的98例患者中45例年龄≥60岁与53例<60岁两组之间OS有统计学差异(P=0.001)。(2)212例原发性MDS患者外周血中全血细胞减少有105例,二系血细胞减少占78例,单系减少占29例；外周血一系减少、二系减少、三系减少三组间OS有统计学差异(P=0.002)。(3)93例患者检测血β2-MG,血β2-MG均数值为2.29±1.18ug/L,其中β2-MG≤2.0ug/L的43例,β2-MG>2.0ug/L的50例,β2-MG<2.0ug/L组患者的Hb、WBC、BPC均值数、生存期较β2-MG>2.0ug/L组高,β2微球蛋白在RA、RAS、RCMD、RAEB-Ⅰ、RAEB-Ⅱ组之间差异无统计学意义(P>0.05)。(4)153例原发性MDS患者行血清LDH检测,其LDH均值为271.80±84.32g/L, LDH在RA、RAS、RCMD RAEB-Ⅰ、RAEB-Ⅱ组之间逐渐增加,但各分型间LDH无显著性差异(p均>0.05)。(5)144例测定了血清SF, SF均数为633.95±225.12g/L, RA与RAEB-Ⅰ比较P<0.05,两组之间有显著性差异,RA与RAEB-Ⅱ之间比较P<0.05,两组之间有显著性差异,其余各组之间比较无显著性差异(p均>0.05)。(6)212例原发性MDS行细胞形态学分析,骨髓有核细胞增生减低占14.6%,红系病态造血改变主要以巨幼样变、巨大红细胞及多核红细胞多见,粒系病态造血主要以核质发育不平衡、假Pelger-Hiiet异常、颗粒改变等为主,巨核系主要以小巨核细胞出现为病态造血为主要表现。56例患者行骨髓活检示骨髓造血组织增生活跃、明显活跃、极度活跃47例(占84%),极度减低、减低9例(占16%)。造血细胞定位紊乱有28例(占50%),粒系不成熟前提细胞异常定位(ALIP)现象有39例(占69.64%),巨核细胞系可见小巨核细胞、病态巨核细胞42例(占75%)；不同骨髓病态造血系数改变在WHO亚型组别间差异无统计学意义(P均>0.05)及其OS的无统计学差异(P=0.062)。(7)122例原发性MDS患者中33例发现克隆性染色体异常,异常核型检出率27.05%,其中以+8、-7/7q-、-5/5q、-20/20q-染色体异常多见,IPSS积分标准进行评估,低危组、中危1组、中危2组、高危组中随着各组危险度越大,染色体异常核型发生率越高,按IPSS染色体核型预后分组,预后差的染色体核型检出率在RA/RAS组,RAEB-Ⅰ组、RAEB-Ⅱ组依次升高,差异有统计学意义(p=0.035)；染色体正常、非复杂核型、复杂核型三组总体生存期差异有统计学差异(p=0.000)。(8)对49例获得随访资料的并有染色体结果的原发MDS患者进行IPSS和WPSS、MDACC分组,结果显示三种预后积分系统在患者确诊时均能对其OS作出准确判断(P<0.0001),随着组别危险度的上升,其平均0S及中位0S均明显下降；三种预后积分系统有较强的联系,但通过生存曲线的比较MDACC评分系统对于判断原发MDS预后生存更有临床价值。结论：(1)原发性MDS患者患病率呈逐年上升趋势,年龄≥60岁患者预后较差。(2)原发性MDS患者外周血多提示有两系或三系下降,三系下降预后越差；不能以骨髓病态造血改变系数判断具体MDS亚型及疾病预后。(3)原发性MDS血β2-MG>2.0ugL组Hb、WBC、BPC均值及生存期(OS)均较β2-MG<2.0ug/L组低,该值的高低与病情进展、疾病的预后有关,可用于对原发性MDS患者的预后分析及病情的监测。(4)原发性MDS患者LDH高,LDH在原发性MDS亚型之间的变异性较大且存在重叠,不能依据LDH水平鉴别MDS亚型。(5)原发性MDS患者SF高,RAEB组明显高于RA组,SF对原发性MDS患者诊断、治疗疗效及预后观察具有一定的临床价值。(6)染色体核型分析对于原发MDS的诊断、预后判断具有十分重要的临床意义。(7) IPSS和WPSS、MDACC预后积分系统均对MDS有较好的预后临床指导意义,但MDACC积分系统对最能反映原发性MDS预后生存,更为有临床价值。更多还原

【Abstract】 Objective:Myelodysplastic syndrome is a heterogeneous group of clonal hematopoietic stem great cell disease.Analysis of the good risk group, peripheral blood, bone marrow morphology typing characteristics of Myelodysplastic syndrome,serum ferritin, lactate dehydrogenase,β2 - microglobulin, bone marrow morphology typing, cytogenetics and other characteristics of myelodysplastic syndrome to investigate prognostic factors and comparison of IPSS, WPSS, MDACC prognostic scoring system. To help clinicians determine the disease more effectively and choose the right treatment.Methods:We retrospectively analyzed 212 cases data of newly diagnosed Primary MDS in the First Affiliated Hospital of Nanchang University from January 2004 to December 2010.98 cases have followed up information.Type the myelodysplastic syndrome according to the WHO classification criteria, summarize and comparison survival rate of the main clinical manifestations, blood, bone marrow routine, bone marrow biopsy, chromosome and the characteristics of treatment options. Because of the number of cases happened to acute myeloidleukemia is small, and thus no longer analysis prognostic factors with acute myeloidleukemia. Compareing the IPSS, WPSS, MDACC line prognostic scoring system based on survival.All the data were analysised by SPSS 16.0 statistical software, measurement data as mean±standard deviation (x±s),indicated that more than three and the number of samples were compared using analysis of variance, if the statistical significance, then use LSD method analysis between two comparison; variety of non-normal data using the rank sum test; count data using Chi-square test, statistical analysis of the level of significance were selected a = 0.05, P<0.05 was considered statistically significant, the survival rate estimated by Kaplan-Meier method and compare survival with Log-Rank Check. Results:(1)212 cases of this group,73 patients≥60 years old,139 patients<60 years old, age range from 14 years old to 86 years old,the median age was 49 years old, and the incidence increased year by year. Older than 60 years between the two groups with less than 60 years old OS, P= 0.001, OS was significantly different between the two groups.(2) 212 cases of primary MDS patients peripheral blood cells three lines decreased have 105 patients, two-line reduction of 78 cases, single-line reduction of 29 cases; three groups of three lines to reduce the P OS= 0.000, the three groups was significantly different of OS.(3) 93 patients detectedβ2-MG,β2-MG were value of 2.29±1.18ug/L, whereβ2-MG≤2.0ug/L in 43 patients,β2-MG> 2.0ug/L in 50 cases, hemoglobin, white blood cells, platelets mean survival time ofβ2-MG≤2.0ug/L group were higher thanβ2-MG> 2.0ug/L group,β2-microglobulin in RA, RAS, RCMD, RAEB-Ⅰ, RAEB-Ⅱdifference between groups have not statistically significant.(4) 153 cases of primary MDS patients detection with LDH, the LDH mean was 271.80±84.32g/L, LDH in RA, RAS, RCMD, RAEB-Ⅰ, RAEB-Ⅱgradually increased, but comparison by LSD test, p> 0.05, between the sub-type of LDH was no significant difference.(5)Of all cases,144 cases did the SF test, SF mean was 633.95±225.12g/L, RA and RAEB-Ⅰcompared by the LSD test P<0.05, between the two groups has significant difference, RA and RAEB-Ⅱby the LSD between comparison test P<0.05, between the two groups has significant difference,In comparison between other groups p> 0.05 have no significant difference.(6)All patients did the bone marrow aspiration cytology, The reduction bone marrow cell proliferation be 14.6%, erythroid dysplasia changes mainly in the megaloblastic changes in red blood cells and multinucleated giant cells, granulocyte dysplasia mainly in the development is not nucleoplasm balance, false Pelger-Huet abnormalities, and changes in particle-based, megakaryocyte dysplasia mainly in appears small megakaryocyte.56 patients did bone marrow biopsy examination. Bone marrow hematopoietic tissue active, significantly active, extremely active in 47 cases (84%), extremely reduced, reducing the 9 patients (16%).28 patients (50%) have hematopoietic cell positioning disorder,39 patients (69.64%) have granulocyte immature premise cells abnormal localization (ALIP) phenomenon,42 patients (75%) have showed small megakaryocytes, pathological megakaryocytes. Bone marrow dysplasia with different coefficients of change in the WHO subtypes has no significant difference between groups (P> 0.05) and has no significant difference of OS (P= 0.062).(7) 122 cases of primary MDS found 33 cases of patients with clonal chromosomal abnormalities, abnormal detection rate of 27.05%, which commonly in +8,-7/7q-,-5/5q,-20/20q- chromosomal abnormalities. Assessment by IPSS score standards, low-risk group, intermediate risk group 1, intermediate risk group 2, high-risk group with higher risk in each group, the higher the incidence of chromosomal abnormalities. Prognosis according to IPSS karyotype groups, and poor prognosis the detection rate of chromosomal karyotypes in RA/RAS groups, RAEB-Ⅰgroup, RAEB-Ⅱgroup in turn increased significantly. Normal chromosomes, non-complex karyotype, complex karyotype differences between the three groups were significantly different overall survival。(8) 49 patients received follow-up data and chromosomal on the primary MDS patients with IPSS and WPSS, MDACC group, three prognostic scoring system showed that the time of diagnosis in patients able to make accurate judgments of their OS (P<0.0001), with the increase in risk groups The average and median OS OS decreased significantly. Three prognostic scoring systems have strong ties, but by comparison of the survival curve for the MDACC grading system to determine the best survival prognosis of primary MDS.Conclusion:(1) The disease of primary MDS gradually increasing in recent years and age≥60 years old poor prognosis.(2) Primary MDS patients with more tips, or three lines, two lines down, down coefficient the more the worse the prognosis; Bone marrow dysplasia can not determine the specific MDS subtypes and prognosis.(3) The hemoglobin, white blood cells, platelets mean survival time ofβ2-MG> 2.0ug/L group were lower than those of (β2-MG< 2.0ug/L, the level of the value have the relationship with progress of the disease and disease prognosis, it can be used in prognosis and disease monitoring of MDS patients.(4) Primary MDS patients with high LDH, LDH in the MDS subtypes have variability between the larger and overlap, according to LDH levels can not distinguish MDS subtypes.(5) SF in MDS patients is high, RAEB group was significantly higher than the RA group, SF has some clinical value to MDS patients on diagnosis, therapy and prognosis.(6) Chromosome to be detected as an important diagnostic indicator of karyotype analysis for the MDS and chromosome is very important in differential diagnosis, prognosis and monitoring of growth and decline of cloning.(7) IPSS and WPSS, MDACC have a better prognosis scoring system guide. MDACC is the best prognosis scoring system for forecast primary MDS.更多还原