Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes

The reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is uncertain and its assessment was the major aim of this study. The different peripheral blood and bone marrow variables required for an adequate morphological classification were blindly evaluated by four cytomorphologists in samples from 50 patients with myelodysplastic syndromes. The degree of agreement among observers was calculated using intraclass correlation coefficient and the generalized kappa statistic for multiple raters. The degree of agreement for the percentages of blasts in bone marrow and peripheral blood, ring sideroblasts in bone marrow, and erythroid, granulocytic and megakaryocytic dysplastic cells was strong (P<0.001 in all instances). After stratifying the percentages according to the categories required for the assignment of World Health Organization subtypes, the degree of agreement was not statistically significant for cases with 5-9% blasts in bone marrow (P=0.07), 0.1-1% blasts in peripheral blood (P=0.47), or percentage of erythroid dysplastic cells (P=0.49). Finally, the interobserver concordance for World Health Organization-defined subtypes showed a moderate overall agreement (P<0.001), the reproducibility being lower for cases with refractory anemia with excess of blasts type 1 (P=0.05) and refractory anemia with ring sideroblasts (P=0.09). In conclusion, the reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is acceptable but the defining criteria for blast cells and features of erythroid dysplasia need to be refined.     

The myelodysplastic syndromes: classification and prognosis

Myelodysplastic syndrome is a neoplastic clonal stem cell disorder characterized clinically by bone marrow failure and a tendency to progress to acute myelogenous leukemia. Dysplasia is the pathologic hallmark. The French-American-British classification served as the gold standard for more than two decades. Under the auspice of the World Health Organization, more than 100 hematopathologists in a 3-year cumulative effort issued the new World Health Organization classification, which recognizes multilineage dysplasia. Refractory anemia with excess blasts is divided into two groups. Chronic myelomonocytic leukemia is reclassified under a separate category. Refractory anemia with excess blasts in the transformation group was omitted. Finally, 5q-syndrome is a new subgroup. In addition to the pathologic classification, various prognostic predictors were formatted into scoring systems. Bone marrow blast percentage, cytopenias, and cytogenetics are the backbone for those prognostic models. The International Prognostic Scoring System is a product of pooled data from previous scoring systems and a useful tool to predict survival and acute myelogenous leukemia evolution. This paper discusses the classification and prognosis of myelodysplastic syndromes and their evolution.     

World Health Organization classification of the acute leukemias and myelodysplastic syndrome

Under the auspices of the European Association of Hematopathologists and the Society for Hematopathology, 100 hematopathologists and clinicians have met together and in subcommittees over a 5-year period. The model used was that developed by the International Lymphoma Study Group, which used morphologic, immunologic, and genetic features. It resulted in the revised European-American Lymphoma classification. The newly proposed leukemia classification uses a similar format and eliminates purely morphologic subtypes that have no current clinical relevance. As with all consensus proposals, these classifications must withstand criticism and debate by potential users.     

Case-control study of risk factors of myelodysplastic syndromes according to World Health Organization classification in a Chinese population

Risk factors of mydelodysplastic syndromes (MDS) remain largely unknown. We conducted a hospital-based case-control study consisting of 403 newly diagnosed MDS patients according to World Health Organization classification and 806 individually gender and age-matched patient controls from 27 major hospitals in Shanghai, China, to examine relation of lifestyle, environmental, and occupational factors to risk of MDS. The study showed that all MDS (all subtypes combined) risk factors included anti tuberculosis drugs [odds ratio (OR)(adj) = 3.15; 95% confidence interval (CI) = 1.22-8.12] as an independent risk factor, benzene (OR(adj) = 3.73; 95% CI = 1.32-10.51), hair dye use (OR = 1.46; 95% CI = 1.03-2.07), new building and renovations (OR = 1.69; 95% CI = 1.11-2.00), pesticides (OR = 2.16; 95% CI = 1.22-3.82), and herbicides (OR = 5.33; 95% CI = 1.41-20.10) as relative risk factors. Risk factors of MDS subtype refractory cytopenia with multiple dysplasia (RCMD) were benzene (OR(adj) = 5.99; 95% CI = 1.19-30.16) and gasoline (OR(adj) = 11.44; 95% CI = 1.31-100.03) as independent risk factors, and traditional Chinese medicines (OR = 2.17; 95% CI = 1.15-4.07), pesticides (OR = 2.92; 95% CI = 1.37-6.25), and herbicides (OR = 12.00; 95% CI = 1.44-99.67) as relative risk factors. Smoking tobacco was significantly associated with refractory anemia with excess of blasts (RAEB) (OR(adj) = 2.43; 95% CI = 1.02-5.77). Education is shown as an independent protective factor against all MDS (OR(adj) = 0.90; 95% CI = 0.83-0.99) and RCMD (OR(adj) = 0.89; 95% CI = 0.79-0.99). These findings suggest that multiple modifiable behavioral, environmental, and occupational factors play a role in MDS etiology, and various MDS subtypes may have different susceptibility.     

进一步规范骨髓增生异常综合征的分型

从系统论和控制论的原理出发 ,骨髓增生异常综合征 (MDS)是目前血液学中信息度较低的一组“灰区病”(greyzonedisease) [1] 。随着近些年来基础与临床研究的不断深入 ,人们发现法、美、英 (FAB)协作组分型法存在不少争议之处。世界卫生组织(WHO)于 1997年对MDS的FAB分型方案进行了较大修正[2 ] ,但仍然是一种有待不断补充、修正与完善的“开放式”分型体系 ,今后必将有另一些亚型调整或进入该分型体系中 ,使之更臻完善。作者认为 ,任何分型均是人为的 ,故而是“约定俗成”的 ,除非确实必要 ,就不宜改动太频 ,太多。现就当前我国MDS…     

World Health Organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes

This study correlated chromosomal defects with French-American-British (FAB)/World Health Organization (WHO) classification subtypes, proposed a revised International Prognostic Scoring System (IPSS) cytogenetic grouping; and established which classification, when used with the IPSS cytogenetic categories, best predicted clinical outcome in the myelodysplastic syndromes (MDS). A higher prevalence of chromosomal defects and distinct defects were observed in patients with multi-lineage dysplasia and a blast cell percentage >10%. Abnormalities of the long arm of chromosome 3, del(7)(q31q35), trisomy 8, del(11)(q14q23), del(12p) and 20q- could be segregated from their respective IPSS cytogenetic categories and used to develop new cytogenetic subgroups. Clinical parameters, FAB/WHO classification, IPSS score and standard or revised cytogenetic categories were statistically relevant for overall survival (OS) and progression-free intervals (PFI) and were included within five distinct multivariate models compared by the Akaike Information Criterion. To predict OS, the best models included age, WHO classification and standard or revised IPSS cytogenetic categories; to predict PFI, the best model included the same variables and revised cytogenetic categories. In conclusion, (i) the WHO classification was associated with a more homogeneous cytogenetic pattern than the FAB classification, (ii) WHO classification and standard/revised IPSS cytogenetic categories were much more effective than IPSS for predicting MDS clinical outcome, (iii) revised cytogenetic subgroups predicted PFI more effectively than standard categories.     

The myelodysplastic syndromes

The myelodysplastic syndromes constitute a fascinating model for monoclonal premalignant disorders. Haemopoiesis is 'dysplastic' with inefficient maturation of a slowly expanding or sometimes of a stable population, of blood cell precursors. About one third of the patients evolve into acute leukaemia, the result of either a progressive expansion of the original clone or a new mutation producing a more malignant subclone. The majority of patients suffer from the results of bone-marrow insufficiency, with pancytopenia and possibly immune deficiency. Characteristic karyotype anomalies involving mainly chromosomes 5, 7 and 8 are seen in half the patients. These same chromosomes are known to carry different oncogenes. The myelodysplastic syndrome occurs mainly in the aged and there is a moderate male preponderance. The incidence is still unknown but is probably similar to that of acute leukaemia. The etiology is also unknown; however, a secondary myelodysplastic syndrome precedes acute myeloid leukaemia, as a late consequence of chemo- and radio-therapy in treated Hodgkin's disease. This suggests that environmental mutagens might also be involved in primary myelodysplastic syndromes. Treatment remains highly unsatisfactory but a few recent developments improve prognosis, at least in the younger patient.     

Prognostic irrelevance of ring sideroblast percentage in World Health Organization-defined myelodysplastic syndromes without excess blasts

The presence of ≥ 15% bone marrow (BM) ring sideroblasts (RS) and < 5% blasts is required for a diagnosis of refractory anemia with ring sideroblasts. We examined the phenotypic and prognostic relevance of this "15%" RS threshold in 200 patients with myelodysplastic syndromes (MDS) without excess blasts and with ≥ 1% RS. The impact of RS% was assessed both as a continuous and categorical variable: < 5% (n = 56), 5%-14% (n = 32), 15%-50% (n = 79), and > 50% (n = 33). RS% correlated (P < .05) directly with age, platelet count, transfusion dependency, BM cellularity, and mutant SF3B1 and inversely with hemoglobin level, multilineage dysplasia, and high-risk karyotype; but did not correlate with IDH mutations. At a median follow-up of 33 months, 156 (73%) deaths and 24 (12%) leukemic transformations were documented. Neither univariate nor multivariable analysis showed significant effect for RS% on overall or leukemia-free survival, suggesting the limited prognostic value of quantifying BM RS in MDS.     

FAB classification of myelodysplastic syndromes: merits and controversies

Guidelines for the definition and diagnosis of myelodysplasia were set out by the French-American-British Cooperative group (FAB), and the resulting framework has greatly helped the now very large number of workers in many scientific disciplines who are actively investigating the myelodysplastic syndromes (MDS). Most patients with MDS can be readily classified into clinically relevant subgroups by correlation of clinical findings with the findings from well-prepared peripheral blood and bone marrow specimens. However, there are several areas where the standard morphological features are insensitive, but integration of these parameters with histology and cytogenetic and molecular techniques may help us in understanding this fascinating disease.     

骨髓增生异常综合征诊断与分型的新认识

骨髓增生异常综合征（ＭＤＳ）是全潜能干细胞水平上的分化障碍引起的一组克隆性恶性血液病。法美英（ＦＡＢ）三国协作组根据血象和骨髓象内的原始细胞数量、髓内环形铁粒幼细胞的多寡,以及周围血单核细胞的增多与否,将ＭＤＳ分为５种亚型（期）,即难治性贫血（Ｒ...     

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.     

World Health Organization and international prognostic scoring system: the limitations of current classification systems in assessing prognosis and determining appropriate therapy in myelodysplastic syndromes

The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders with a wide range of clinical and pathologic manifestations. A number of prognostic and morphologic classifications have been developed that can be helpful in terms of defining the characteristics of populations of patients in clinical trials and longitudinal observational studies, and sometimes in allowing comparisons of the outcomes of different treatment approaches. They are less helpful in guiding treatment decisions in individual patients and, unfortunately, provide little insight into the poorly understood biology of MDS. The merits and limitations of these classification systems are discussed.     

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。