骨髓增生异常综合征FAB和WHO分型的临床评价

目的:评价和分析骨髓增生异常综合征(MDS)从FAB分型到WHO分型的发展和临床意义。方法:对MDS患者分别用FAB分型及WHO分型进行分型,并对形态学、临床、实验室检查及预后资料进行对比分析。结果:MDS和急性髓性白血病(AML)均可出现病态造血。FAB分型中难治性贫血(RA)、原始细胞过多难治性贫血(RAEB)、转化中的原始细胞过多难治性贫血(RAEB-T)及AML之间生存率差异有统计学意义。WHO分型中RA与难治性血细胞减少伴多系增生异常(RCMD)之间生存率差异无统计学意义,RA与RAEB、RCMD与RAEB之间生存率差异有统计学意义,RAEB-Ⅰ与RAEB-Ⅱ之间生存率有显著差异。结论:WHO分型将FAB分型中的RA分为RA和RCMD并未显示出临床优越性。RAEB-T生存期比AML更短,因而将RAEB- T归为急性白血病,对临床治疗有好处。WHO分型按照原始细胞百分比将RAEB分为RAEB-Ⅰ和RAEB-Ⅱ,对临床诊断、治疗和预后有益。     

骨髓增生异常综合征线粒体呼吸链酶复合体的变化

目的:研究骨髓增生异常综合征(MDS)患者骨髓单个核细胞线粒体呼吸链的功能变化并分析其与MDS的关系.方法:测定26例MDS患者与10例骨髓象正常者的单个核细胞线粒体呼吸链酶复合体Ⅰ、Ⅲ、Ⅳ的活性.结果:MDS患者呼吸链酶复合体Ⅰ、Ⅲ、Ⅳ的活性明显低于对照组(P＜0.05);线粒体呼吸链酶复合体Ⅰ、Ⅲ的活性在RAEB-Ⅰ、RAEB-Ⅱ组与RA、RARS组的差异无统计学意义(均P＞0.05),而酶复合体Ⅳ的活性在RAEB-Ⅰ、RAEB-Ⅱ组较RA、RARS组高,差异有统计学意义(P＜0.05).结论:线粒体呼吸链酶复合体的活性在MDS患者中降低,可能与MDS的病态造血及无效造血有关.     

骨髓增生异常综合征WHO分型标准的临床应用

目的:分析世界卫生组织(WHO)与法-美-英协作组(FAB)2种标准分型结果的不同点,探讨WHO分型标准临床应用价值.方法:选择179例骨髓增生异常综合征(MDS)患者,其中168例是2003年～2006年确诊的原发性MDS,11例有血细胞减少伴有病态造血的病例.对179例患者按FAB与WHO 2种分型方案重新进行评价.结果:按FAB分型标准:RA 50例,RAS 9例,RAEB 62例,RAEB-T 23例,CMML 24例,11例未明确诊断,只描述了形态学特点.按WHO分型标准:RA 14例,RAS 5例,RCMD 36例,RCMD-RS 4例,MDS-U 5例,6例不能确诊.结论:2种分型方案有较大差异,由于WHO分型中RA只限于贫血, 单纯红系病态造血; 将2系以上血细胞减少,2系以上病态造血,原始细胞<5%的病例归入了WHO新的亚型RCMD.通过本组病例分析:RCMD介于RA与RAEB中间,原始细胞不增多与RA相似,临床症状、实验室检查、血细胞形态学特点与RAEB相似.WHO将RAEB根据原始细胞数量分为两型,RAEB-T归入急性白血病,CMML归入骨髓增殖性疾病中,更符合临床的实际需要,有利于临床医师对治疗方案的选择.WHO分型方案仍需补充、修正、给血液学工作者提供更为完善的诊断标准.     

原发骨髓增生异常综合征患者IPSS及染色体核型的临床分析

目的:比较原发性骨髓增生异常综合征(MDS)患者WHO(2001)分型与FAB分型的IPSS染色体核型分析及预后的相关性分析。方法:经FAB标准确诊的原发MDS的患者重新按WHO标准分型,对2种结果的IPSS及染色体异常与各亚型的关系进行分析。结果:按FAB分型各亚型的IPSS及染色体异常无显著性差异,按WHO分型的难治性细胞减少伴多系增生异常(RCMD)与难治性贫血(RA)患者染色体异常率有统计学意义(66.6%,41.7%,P<0.01),RAEB-2高危组比例明显高于RAEB-1组(25%,0%,P<0.01)。结论:原发MDS的WHO分型与FAB分型相比,前者与预后的相关性更好。     

骨髓增生异常综合征研究进展

骨髓增生异常综合征(myelodysplastic syndromes,MDS)亚克隆在低危组就达到很高比例,驱动基因导致疾病进展。RNA剪接子复合物基因突变与MDS有较高相对特异性,并与疾病临床表现和预后相关。MDS的难治性血胞减少伴单系病态造血(refractory cytopenia with unilineage dysplasia,RCUD)中各亚型,MDS-U(MDS-unclassified,MDS-U)和MDS-RCMD(MDS-refractory cytopenia with multilineage dysplasia,MDS-RCMD)之间,病态造血、生存率和转白率无显著差异。IPSS的修订版和合并症指数更好地对MDS患者的预后和机体状态做出评价。规则去铁治疗可能改善MDS患者生活质量、生存期。促红细胞生成素早期失败者转白率和生存率均差。去甲化药物中阿扎胞苷可能疗效更佳。     

骨髓增生异常综合征435例WHO分型和细胞遗传学分析

目的 探讨我国骨髓增生异常综合征(MDS)WHO亚型分布和细胞遗传学异常特点,并与西方国家进行比较.方法 采用前瞻性方法收集了协作组435例MDS患者,进行WHO分型,采用染色体G显带和荧光原位杂交(FISH)技术进行细胞遗传学分析.结果 MDS中位发病年龄为58(18～90)岁.难治性血细胞减少伴多系发育异常(RCMD)病例比例最高,约占69.6%(303/435),其他亚型依次为难治性贫血伴原始细胞增多(RAEB)24.1%(105/435)、难治性贫血(RA)2.3%(10/435)、不能分类MDS(MDS-U)2.3%(10/435)、难治性贫血伴环状铁粒幼细胞增多(RAS)1.2%(5/435)和5q-综合征0.5%(2/435),而西方国家RA、RAS、5q-综合征比例较高,RCMD亚型比例低于中国.11例染色体检查失败,424例染色体检查成功的染色体克隆性异常率为38.7%(164/424),其中RAEB-Ⅰ异常率最高62.5%(25/40),其次RAEB-Ⅱ 48.4%(30/62)、RCMD 34.5%(102/296).常见的染色体异常依次为:+8为12.7%(54/424)、复杂核型为9.O%(38/424)、染色体易位为7.8%(33/424)、-20q为6.6%(28/424)、-7/-7q为5.2%(22/424)、-5/-5q为4.2%(18/424),而国外最常见的是-5/-5q、-7/-7q、+8、11q及12p/12q异常.以国际预后积分系统染色体预后分组,染色体预后良好组68.2%(289/424),预后中等组19.1%(81/424),预后不良组12.7%(54/424).有17例患者因为异常细胞的比例偏低,染色体检查正常,但FISH检测到低水平的异常.结论 我国MDS的WHO亚型分布与染色体异常分布与西方国家不同.FISH和常规染色体检查相结合,可以提高检测的灵敏度.     

骨髓增生异常综合征转化为急性白血病的高危因素分析

目的:探讨影响骨髓增生异常综合征(MDS)转化为急性白血病的高危因素。方法:回顾性分析我院收治的101例MDS患者的转白时间、转白亚型、临床特征、实验室数据等临床资料。结果:101例MDS患者中,34.6%(35/101)转化为急性髓系白血病,中位转白时间7.5(0.5~53)个月,中位生存时间40.7(1~87)个月。单因素分析发现,染色体核型、骨髓原始细胞比例、血细胞减少系数、病态造血累及系数、WHO分型均影响MDS患者的转白率(均P0.05)。多因素分析发现,染色体核型、病态造血系数、WHO分型是MDS向急性白血病转化的独立危险因素(均P0.05)。转白组患者较未转白组患者的生存期明显缩短(11个月∶45个月)。结论:MDS是一类高风险向急性白血病转化的疾病,根据相关高危因素,对其进行预后评估,从而为个体化治疗提供临床依据,对延长患者转白时间及总生存时间具有重要意义。     

骨髓增生异常综合征99例临床分析

目的探讨骨髓增生异常综合征(MDS)患者WHO亚型分布、细胞遗传学特点及其与MDS诊断分型、疾病进展和预后的关系。方法回顾性分析2001年1月至2007年12月安徽医科大学附属安徽省立医院血液科收治的99例成人原发MDS患者的染色体核型、WHO分型及预后情况,随访观察并进行相关性研究。结果99例MDS患者难治性贫血(RA)型26例(26.26%);难治性贫血伴环形铁幼粒细胞增多(RAS)型6例(6.06%);难治性贫血伴多系发育异常(RCMD)型23例(23.23%);难治性贫血伴原始细胞增多(RAEB)型44例(44.44%)。按IPSS预后分组,中危Ⅱ和高危组的染色体核型异常检出率明显高于低危和中危Ⅰ组(χ2=17.88,P<0.01);中危Ⅱ和高危组患者进展为急性白血病的发生率明显高于低危和中危Ⅰ组(χ2=40.22,P<0.01)。按IPSS染色体核型分组,预后好、中、差的患者中位存活期分别为45(95%CI:39~51)、37(95%CI:25~49)和23(95%CI:13~31)个月,Log-rank检验三组总体生存(OS)率差异有统计学意义(P=0.010)。结论中国有别于西方国家MDS患者的WHO亚型分布,染色体核型分析是MDS诊断分型及预后评估的重要指标。     

骨髓增生异常综合征患者骨髓单个核细胞免疫表型特点及临床意义

目的:探讨骨髓增生异常综合征(MDS)患者骨髓单个核细胞免疫表型特点及临床意义。方法:回顾性分析48例MDS患者免疫表型,对比各亚型间免疫表型表达阳性率的高低,并评估其与IPSS积分的相关性。结果:48例MDS患者骨髓单个核细胞表达CD34、CD117、CD11b、CD33、CD13为主,RAEB1及BAEB2患者CD34、CD117及早期髓系抗原CD33、CD13阳性表达率较RCMD患者增高(P<0.05);骨髓原始细胞比例与CD34、CD117、CD13及CD33阳性表达率呈正相关;对这些患者进行IPSS积分系统评估,高危组CD34及CD117表达阳性率较中危1组升高(P<0.05),CD34表达阳性率与IPSS积分呈正相关。结论:MDS患者进行骨髓单个核细胞免疫表型检测对病情评估及预后判断有重要价值。     

老年骨髓增生异常综合征患者的临床特点和预后分析

目的 探讨老年骨髓增生异常综合征(Myelodysplastic syndrome,MDS)患者的临床特点、临床转归及影响其预后的相关因素,评估国际预后积分系统(IPSS)在老年MDS预后中应用的意义.方法 选取2000年1月～2006年12月老年MDS患者(≥60岁)病例31例,因病采用不同治疗方案并追踪其临床病情变化情况.同期选取50例非老年性MDS患者(＜60岁)作为对照.所有生存率采用寿命表法,所有生存率函数曲线均采用Kaplan-Meier法分析.结果 31例老年MDS患者中位发病年龄为65岁.初诊时48.39%的患者有全血细胞减少,35.48%的患者合并感染.按WHO分型难治性白细胞减少伴多系增生异常(RCMD)和伴原始细胞增多的难治性蛋白-Ⅱ型(RAEB-Ⅱ)比例最高,共占84.62%.按1976年法、美、英三国制定的白血病分类法(FAB分型)RAEB患者比例最高,占61.29%.骨髓细胞形态学提示各系均有不同程度病态造血,以二系病态造血最多见(54.84%).19例骨髓活检患者中57.89%出现病态造血,47.37%出现幼稚前体细胞异常定位(ALIP)现象.13例患者进行细胞遗传学检查,染色体异常率为38.46%.截止随访结束,死亡26例(83.87%),中位生存期12.448个月,61.54%患者死于感染.老年组总存活期(overall survival,OS)显著低于非老年组患者(P＜0.000 1).IPSS不同危险组别的老年组(P＝0.004 5)和非老年组(P＜0.000 1)的总存活期均有显著差异.对各项临床指标的单因素分析结果表明,IPSS染色体分组(P＝0.002 4)和血小板计数(P＝0.041)是影响老年MDS预后的重要因素.不同治疗方法对老年MDS患者总存活期未见有明显区别(P＝0.912).结论 老年MDS患者以预后相对较差亚型常见,感染是其初诊及死亡的常见原因.相比非老年性患者,老年性MDS患者有显著较差的预后,IPSS及其染色体分组仍是判断老年MDS预后的重要指标.     

Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification

Morphology is the basis of the diagnosis of myelodysplastic syndromes (MDS). The WHO classification offers prognostic information and helps with the treatment decisions. However, morphological changes are subject to potential inter-observer variance. The aim of our study was to explore the reliability of the 2008 WHO classification of MDS, reviewing 100 samples previously diagnosed with MDS using the 2001 WHO criteria. Specimens were collected from 10 hospitals and were evaluated by 10 morphologists, working in five pairs. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. The second observer was blinded to the clinical and laboratory data, except for the peripheral blood (PB) counts. Nineteen cases were considered as unclassified MDS (MDS-U) by the 2001 WHO classification, but only three remained as MDS-U by the 2008 WHO proposal. Discordance was observed in 26 of the 95 samples considered suitable (27 %). Although there were a high number of observers taking part, the rate of discordance was quite similar among the five pairs. The inter-observer concordance was very good regarding refractory anemia with excess blasts type 1 (RAEB-1) (10 of 12 cases, 84 %), RAEB-2 (nine of 10 cases, 90 %), and also good regarding refractory cytopenia with multilineage dysplasia (37 of 50 cases, 74 %). However, the categories with unilineage dysplasia were not reproducible in most of the cases. The rate of concordance with refractory cytopenia with unilineage dysplasia was 40 % (two of five cases) and 25 % with RA with ring sideroblasts (two of eight). Our results show that the 2008 WHO classification gives a more accurate stratification of MDS but also illustrates the difficulty in diagnosing MDS with unilineage dysplasia.     

Myelodysplastic syndromes, from French-American-British to World Health Organization: comparison of classifications on 431 unselected patients from a single institution.

In 1999 a working group of the World Health Organization (WHO) published a revised classification for myelodysplastic syndromes (MDS): RA, RARS, refractory cytopenia with multilineage dysplasia (RC+Dys), RAEB I and II, del (5q) syndrome, and MDS unclassifiable. Chronic myelomonocytic leukemia (CMML) and RAEB-t were excluded. Standard French-American-British (FAB) and new WHO classifications have been compared in a series of patients (n = 431) from a single center, analyzing morphologic, clinical, and cytogenetic data. According to the WHO findings, dysgranulocytopoiesis or dysmegakaryocytopoiesis only were found in 26% of patients with less than 5% medullary blasts. These patients are thus unclassified and should remain in the subgroups RA and RARS. Splitting of heterogeneous RAEB into 2 subgroups according to blast count was supported by a trend to a statistically significant difference in the single-center study population. Patients with CMML whose white blood cell counts are above 13 000/microL may be excluded from the MDS classification, as warranted by WHO, but a redistribution of patients with dysplastic CMML according to medullary blast count leads to more heterogeneity in other WHO subgroups. Although the natural courses of RAEB-T and acute myeloid leukemia (AML) with dysplasia are different, comparable median survival durations after treatment in patients with RAEB-T and AML were in favor of the proposed 20% medullary blast threshold for AML. The homogeneity of subgroups was studied by evaluating prognostic scores. A significant shift into lower IPSS risk groups was evident in the new classification. These data cannot provide evidence for the new WHO proposal, which should not be adopted for routine clinical use at present. Some of its aspects can provide a starting point for further studies involving refined cytogenetics and clinical results.     

The myelodysplastic syndromes: diagnosis, molecular biology and risk assessment

Myelodysplastic syndromes (MDS) are heterogeneous group of neoplastic clonal stem cell diseases characterized by dysplastic morphological features and clinical bone marrow failure. The FAB (French-American-British) system served as the gold standard for MDS classification for more than two decades. The WHO classification, built on the backbone of FAB classification, is an attempt to further improve the prognostic value of MDS classification as well as establish its clinical utility as a tool to select different treatments. In this article we review the epidemiology, pathogenesis, molecular biology, diagnosis and classification of MDS. We highlight the major differences between the FAB classification and the WHO MDS classification. We discuss in more detail the experience of using the new WHO classification since its publication and review the studies that tried to validate the prognostic value of the new classification or apply it to predict clinical responses to various treatments.     

The clinical implications of the World Health Organization's classification of myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplastic clonal stem cell diseases characterized by dysplastic morphological features with a varying percentage of leukemic blasts and clinical bone marrow failure. The French-American-British (FAB) system served as the gold standard of MDS classification for more than two decades. The World Health Organization (WHO) classification, built on the backbone of the FAB classification, is an attempt to further improve the prognostic value of MDS classification as well as to establish its clinical utility as a tool to select different treatments. In this article we highlight the major differences between the FAB classification and the WHO MDS classification. We discuss in more details the experience of using the new WHO classification since its publications and review the studies that tried to either validate the prognostic value of the new classification or apply it to predict clinical responses to various treatments.     

Clinical significance of WHO classification and MDS 2000 classification in myelodysplastic syndromes

Excluding chronic myelomonocytic leukemia, a total of 92 consecutive patients with myelodysplastic syndrome showing less than 20% blasts in the bone marrow were analyzed. We evaluated the clinical significance of the WHO and MDS 2000 classifications by reviewing each MDS patient according to the classification. The WHO criteria classified the MDS patients into 36 with RA, 22 with RCMD and 33 with RAEB, whereas according to the MDS 2000 criteria there were 19 RAEB-I patients and 15 RAEB-II patients. Based on the WHO classification, the RCMD patients had higher platelet counts and percentages of blasts among BM cells than the RA patients (P = 0.0018, P = 0.0001). Twenty percent of the RA patients, 44.8% of the RCMD patients, and 70.8% of the RAEB patients had cytogenetic abnormalities. Among them, the poor karyotype was present in 6.7% of the RA patients, 21.0% of the RCMD patients and 41.6% of the RAEB patients. The rate of acute leukemia death was 14.3% in the RA patients, 67.7% in the RAEB patients and 50.0% in the RCMD patients. Analysis of survival times revealed significant differences between RA and RCMD patients (P = 0.0482). The clinical features of RCMD patients were intermediate between those of RAEB and RA patients. There was no difference between the clinical features of the RAEB-I and RAEB-II patients in the MDS 2000 classification.     

Can t(8;21) oligoblastic leukemia be called a myelodysplastic syndrome?

The new World Health Organization (WHO) classification of hematologic malignancies has incorporated t(8;21) myelodysplastic syndromes (MDS) according to the French-American-British classification into the category of acute myeloid leukemia (AML) with t(8;21)(q22;q22), while our knowledge about clinicopathological features of t(8;21) oligoblastic leukemia is still limited. We present our experience with 12 patients meeting the FAB diagnostic criteria of MDS and having t(8;21), who were compared to 43 t(8;21) AML patients. The MDS and AML patients shared most hematomorphologic, immunophenotypic, and clinical features, whereas the differences lay along myeloid maturation. The MDS patients had higher percentages of circulating neutrophils and marrow myeloid cells beyond promyelocytes than the AML patients. The incidence of Auer rods in mature neutrophils in MDS was significantly higher than that in AML, and furthermore, the neutrophils in MDS more commonly contain t(8;21) than in AML. Our findings support the rationale for the WHO classification, and future studies on large patient populations should help clarify whether the spontaneous differentiation potential could be actively associated with a hematological manifestation of t(8;21) leukemias.     

Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution

This study evaluated whether the NCCSS truly improves the prognostic stratification of 630 consecutive de novo MDS patients and established which cytogenetic grouping [NCCSS or International Prognostic Scoring System (IPSS)], when combined with the WHO classification, best predicted the clinical outcome of myelodysplastic syndromes (MDS). The frequency of chromosomal defects was 53.8%. Clinical parameters, including number of cytopenias, WHO classification, IPSS cytogenetic categories and scores, NCCSS were all relevant for overall survival (OS) and leukemia‐free survival (LFS) and were included in six distinct multivariate models compared by the Akaike Information Criterion (AIC). The most effective model to predict OS included the number of cytopenias, the WHO classification and the NCCSS, whereas the model including the number of cytopenias, blast cell percentage and the NCCSS and the model including the number of cytopenias the WHO classification and the NCCSS were almost equally effective to predict LFS. In conclusion, the NCCS (i) improves the prognostic stratification of the good and poor IPSS cytogenetic categories by introducing the very good and the very poor categories; (ii) is still incomplete in establishing the prognostic relevance of rare/double defects, (ii) applied to patients who receive supportive treatment only identifies five different prognostic subgroups, but applied to patients treated with specific therapies reveals only a trend toward a significantly different OS and LFS when patients of the poor and intermediate cytogenetic categories are compared, (iii) combined with the WHO classification is much more effective than the IPSS in predicting MDS clinical outcome. Am. J. Hematol. 88:120–129, 2013. © 2012 Wiley Periodicals, Inc.     

Characteristics of acute myeloid leukemia with myelodysplasia‐related changes: A retrospective analysis in a cohort of Chinese patients

We retrospectively analyzed 449 patients with AML under the WHO classification of AML 2008 and probed implications of this classification in diagnosis and treatment of acute myeloid leukemia with myelodysplasia‐related changes (AML‐MRC) among them. The clinical presentations, biological features, treatments, and prognosis of patients diagnosed with AML‐MRC were analyzed and compared with those of AML not otherwise specified (AML‐NOS). In all patients, 115 (25.6%) were diagnosed as AML‐MRC including 64 males and 51 females with median onset age of 48 years (range from 17 to 78). Their complete remission (CR) rate was 60.9% and relapse rate was 57.1%. The observed median overall survival (OS) and disease‐free survival (DFS) were 10 and 5 months, respectively, which was significantly shorter than those of AML‐NOS patients (P < 0.05). The prognosis of AML‐MRC patients with myelodysplastic syndrome (MDS)‐related cytogenetics sole was similar to those with history of MDS or myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Patients with MDS‐related cytogenetic abnormalities and/or history of MDS or MDS/MPN predisposed significantly shortened CR, OS, and DFS than AML‐MRC patients with only multilineage dysplasia (MLD) and AML‐NOS patients (P < 0.05). Multivariate analysis showed that age, cytogenetics, and history of MDS or MDS/MPN were independent prognostic factors. Patient diagnosed as AML‐MRC presented distinctive clinical and biological features. Presence of MLD does not change the prognosis. Am. J. Hematol. 89:874–881, 2014. © 2014 Wiley Periodicals, Inc.     

Epidemiology, classification and prognosis of adults and children with myelodysplastic syndromes

Myelodysplastic syndromes (MDS) belong to the most frequent bone marrow diseases with a crude incidence of about 4 in 100,000 per year. The diagnosis of MDS still is mainly based on morphologic findings in blood and marrow. The new WHO classification system takes into account the medullary and peripheral blast count as well as the degree of dysplasia in the different cell lines. To correctly identify MDS types, cytogenetic evaluation is of importance, as the WHO classification introduced the entity MDS with del(5q), which is characterized by special morphologic and hematologic features. The separation of MDS from acute leukemias has been redefined using a cutoff value of 20% peripheral and/or medullary blasts. The International Prognostic Scoring System still is the gold standard in prognostication, but new items like transfusion need will be used more and more and have been incorporated into the WHO adapted Prognostic Scoring System. In childhood, MDS is uncommon, accounting for less than 5% of all hematopoietic neoplasms in patients less than 14 years of age. To accommodate for the characteristics of pediatric MDS, a simple classification scheme based on morphological features and conforming with the WHO suggestions was proposed. The dysplastic prodrome of acute myeloid leukemia in Down syndrome is classified within myeloid leukemia in Down syndrome and excluded from the population-based studies of MDS.