Analysis of mutations of 14 genes among 87 patients with myelodysplastic syndrome / 中华医学遗传学杂志

Objective@#To explore the correlation of genetic mutations and clinical features of myelodysplastic syndromes (MDS) with scores of Revised International Prognostic Scoring System (IPSS-R).@*Methods@#Eighty-seven patients with de novo MDS were enrolled. Mutations of MDS-related genes and clinical features were used to determine the incidence and subtype of mutations. Clinical features and IPSS-R scores of the patients with high frequency mutations involving TET2, TP53, ASXL1, RUNX1 and SF3B1 genes were compared.@*Results@#Fifty-four patients (62.1%) harbored at least one point mutation. The incidences of various mutations were significantly different, with the incidence of MDS-EB-2 being 100% and MDS-SLD being only 38.9%. Compared with the wild types, patients harboring mutations had higher lactate dehydrogenase, higher β2 microglobulin, higher percentage of bone marrow blast cells and lower hemoglobin levels (P=0.027, <0.01, <0.01, 0.046, respectively). The IPSS-R scores of MDS patients with mutations were significantly higher than the wild types (P<0.01). The IPSS-R scores of the TP53 mutation groups were 7.82±1.83, which was significantly higher than the control group (3.77±1.66, P<0.01). No difference was found between the IPSS-R between patients carrying TET2, ASXL1, RUNX1, and SF3B1 mutations or the wild types (P>0.05).@*Conclusion@#Genetic mutations are commonly found in MDS. MDS patients with mutations have unique clinical laboratory characteristics. Although the prognostic value of most genes is controversial, TP53 is an definite indicator of poor prognosis.

Prognostic scoring of myelodysplastic syndromes / 天津医药

@#Myelodysplastic syndrome (MDS) is a clonal disease derived from the hematopoietic stem cells, with a high degree of heterogeneity and complexity. The prognostic evaluation of MDS is a core problem of this disease, mainly because the complex pathogenesis (genomics, epigenetics, bone marrow microenvironment and immune factors) determines the heterogeneity of clinical characteristics (heterogeneity of age, infection, risk of bleeding, and comorbidities) and differential clinical outcome (bone marrow failure and leukemia transformation). Therefore, how to comprehensively consider various prognostic factors to establish a prognostic score system to predict the prognosis and clinical outcome of patients with MDS is very important. In the past two decades, many MDS scholars have devoted themselves to the study of various MDS prognostic scoring systems. Typical prognostic scoring systems such as the International Prognostic Scoring System (IPSS) and its revisions (IPSS-R) have been widely used. In addition, based on these new prognostic factors, the prognostic scoring system has also showed good prognostic value with the discovery of many clinical markers and molecular changes. This review summarizes the prognostic scoring system and new prognostic factors of MDS in recent years for reference in clinical practice.

No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome

BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSIONS: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

Study on application of the Revised International Prognostic Scoring System in myelodysplastic syndrome / 重庆医学

Objective To investigate the clinical and cytogenetic features of myelodysplastic syndrome (MDS) ,and to investigate the application of the International Prognostic Scoring System Revised (IPSS-R) in myelodysplastic syndrome .Methods A retro-spective analysis was conducted on 112 patients diagnosed with MDS on basis of French-American-British(FAB) and World Health Organization(WHO) criterion .Conventional cytogenetics are performed to investigated the cytogenetics changes .Results Karyo-type abnormalities are found in 46(41 .1% ) patients .Cytogenetics subgroups are devided into 5 groups according to IPSS-R criteri-on :very good ,good ,intermediate ,poor ,very poor ,which account for 2 cases(1 .8% ) ,48 cases (42 .9% ) ,41 cases (36 .6% ) ,10 ca-ses (8 .9% ) ,11 cases (9 .8% ) ,with a median survival time(MS) 59 ,36 ,15 ,10 month respectively ,except for very good .Conclusion It is of great guiding significance of IPSS-R criteria for prognostic stratification .

A Clinical Study on Myelodysplastic Syndrome in Childhood / 대한소아혈액종양학회지

PURPOSE: This study was undertaken to investigate the clinical characteristics and prognostic predictors of myelodysplastic syndrome (MDS) in childhood. Method: The characteristics and laboratory findings of 20 patients seen at Asan Medical Center for the past 10 years from September 1989 to August 1998 were reviewed retrospectively with regard to the new International Prognostic Scoring System (IPSS) proposed by International MDS Risk Analysis Workshop. RESULTS: 1) In 20 children with MDS we studied, there was no age or sex predilection unique to the subgroups of MDS. 2) 19 cases (95%) out of the 20 had pallor at the time of diagnosis. Other major clinical findings were bleeding tendency in 11 (55%), fever in 8 (40%), hepatosplenomegaly in 8 (40%), and lymphadenopathy in 3 (15%). 3) The hemoglobin level was less than 10 g/dL in all cases and absolute neutrophil count (ANC) was decreased in 11 cases, thrombocytopenia in 15 cases. Pancytopenia was noted in 8 cases (40%). 4) Of the 20 cases, 9 had refractory anemia (RA), 3 refractory anemia with excess blasts (RAEB), 3 refractory anemia with excess blasts in transformation (RAEBIT), and 5 juvenile chronic myelogenous leukemia (JCML). 5) All RA patients were Intermediate (INT)-1 risk group, and all RAEB children were INT-2 risk group. The 3 cases of RAEBIT fell into INT-1, INT-2, and high risk group. Three cases of JCML were INT-1 group, and 2 cases INT-2 group. 6) Seven cases out of 13 INT-1 group had mean survival of 20.2 month (6~57 month), but only 1 out of 6 INT-2 survived. One case of high risk group succumbed to disease 50 months after diagnosis. CONCLUSION: These results showed that there was no age or sex predilection for the specific subgroup of childhood MDS. All the FAB subtypes of the childhood MDS except RA subgroup had poor survival. In this study, we found the IPSS seemed to be a prognostic predictor in childhood MDS but more cases are needed to confirm the validity of IPSS.