scholarly journals SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 569-572 ◽  
Author(s):  
Mrinal M. Patnaik ◽  
Terra L. Lasho ◽  
Janice M. Hodnefield ◽  
Ryan A. Knudson ◽  
Rhett P. Ketterling ◽  
...  
Keyword(s):  
World Health Organization ◽  
Myelodysplastic Syndromes ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
World Health ◽  
Refractory Anemia ◽  
Multilineage Dysplasia ◽  
Ring Sideroblasts ◽  
Health Organization ◽  
Risk Categorization

SF3B1 mutations were recently reported in myelodysplastic syndromes (MDSs), especially in the presence of ring sideroblasts (RSs). We sought to define the interaction between SF3B1 mutations, morphology, karyotype, and prognosis in MDS with more than or equal to 15% RS (MDS-RS). We studied 107 patients with MDS-RS, including 48 with refractory anemia with RS (RARS), 43 with refractory cytopenia with multilineage dysplasia (RCMD)-RS, 11 with refractory anemia with excess blasts-1 (RAEB1)–RS, and 5 with RAEB2-RS. SF3B1 mutations were detected in 53 (∼ 50%) patients: 35 RARS (73%), 16 RCMD-RS (37%), and 2 RAEB1-RS (18%). In univariate analysis, the presence of SF3B1 mutations was associated with better overall (P < .01) and leukemia-free (P < .01) survival; however, in both instances, significance was completely accounted for by World Health Organization morphologic risk categorization. In other words, when RARS and RCMD-RS were analyzed separately, there was no additional prognostic value from the presence or absence of SF3B1 mutations.

SF3B1 Mutations Are Prevalent in Myelodysplastic Syndromes with Ring Sideroblasts but Do Not Hold Independent Prognostic Value

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 460-460 ◽  
Author(s):  
Mrinal M. Patnaik ◽  
Terra L Lasho ◽  
Janice M Hodnefield ◽  
Ryan A Knudson ◽  
Rhett P Ketterling ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
World Health ◽  
Refractory Anemia ◽  
Ring Sideroblasts ◽  
Risk Categories ◽  
Good Risk

Abstract Abstract 460 Background: SF3B1 mutations were recently reported to occur in myelodysplastic syndromes (MDS), especially in the presence of ring sideroblasts (RS) (Papaemmanuil et al. Leukemia Research 2011, Volume 35, Supplement 1, page S18). We sought to accurately define the interaction between SF3B1 mutations, bone marrow morphology, karyotype and prognosis in MDS with ≥15% RS (MDS-RS). Methods: Mayo Clinic databases and cell banks were queried to identify patients with MDS and ≥15% RS (MDS-RS). All study patients were required to have undergone bone marrow examination and cytogenetic evaluation at diagnosis. Pathology slides, including iron stains, were centrally re-reviewed to accurately quantify bone marrow RS percentage and confirm World Health Organization (WHO) morphologic categories. Detailed analysis of clinical and cytogenetic parameters was performed to risk stratify patients according to the revised International Prognostic Scoring System (IPSS-R) (Greenberg et al. Leukemia Research 2011, Volume 35, Supplement 1, page S6). All patients were annotated for their mutational status involving JAK2, MPL and IDH. PCR sequencing was used to identify SF3B1 mutations. Results I: Baseline patient information: The study is currently ongoing; to date, results are availab1e in 88 patients (median age 72 years, 69% males) including 36 (41%) patients with refractory anemia with RS (RARS), 36 (41%) with refractory cytopenia with multilineage dysplasia and ≥15% RS (RCMD-RS), 11 (12%) with refractory anemia with excess blasts (RAEB)-1 and ≥15% RS (RAEB1-RS) and 5 (6%) with RAEB2-RS. Median (range) values were 9.1 g/dL (5.8–15.7) for hemoglobin, 4.1 × 109/L (1.2–35.2) for leukocytes and 164 × 109/L (6–585) for platelets. IPSS-R risk categories were 20% very good, 49% good, 11% intermediate, 3% poor and 16% very poor. Karyotype was normal in 60%, other very good/good risk 16%, intermediate-risk 2%, and poor/very poor in 22%; 14% had monosomal karyotype (MK). Six (7%), four (5%) and zero (0%) patients displayed IDH, JAK2 or MPL mutations. Red cell transfusion need was documented in 27 (31%) patients. Results II: Prevalence and distribution of SF3B1 mutations and clinical correlates: SF3B1 mutations (all heterozygous) were detected in 40 (∼46%) of all 88 study patients: 25 (63%) K700E, 6 (15%) K666N/Q/R, 3 (8%) E622D, 2 (5%) H662D/Q, 2 (5%) Y623C, 1 (3%) R625C, and 1 (3%) T663I. One patient each displayed both SF3B1K700E and IDH2R140Q or SF3B1K700E and JAK2V617F. SF3B1 mutational frequencies were 69% for RARS, 36% for RCMD-RS, 18% for RAEB1-RS and 0% for RAEB2-RS (p=0.0007). SF3B1 mutations clustered with normal (59%) and other very good/good risk (57%) karyotype and were infrequent in poor/very poor karyotype (5%; p=0.0004). Additional significant correlations were noted between SF3B1 mutations and lower IPSS-R risk category (p=0.0004), advanced age (p=0.006), higher platelet count (p=0.0003). Results II: SF3B1 mutations and prognostic relevance in MDS-RS: To date, 68 (∼77%) deaths and 10 (∼11%) leukemic transformations have been documented. Median follow-up for living patients was 82 months. Univariate survival analysis considering all 88 study patients identified the following as strongly significant risk factors: IPSS-R (p<0.0001), WHO morphologic categories (p<0.0001), cytogenetic risk categories (p<0.0001), and transfusion need (p=0.0003). In multivariable analysis, only IPSS-R and transfusion need remained significant. In univariate analysis, the presence of SF3B1 mutations was significantly associated with better overall (p=0.04) and leukemia-free (p=0.03) survival; however, in both instances, significance was completely accounted for by WHO morphologic risk categorization and the morphology-adjusted p values were 0.6 and 0.2, respectively. In other words, when RARS and RCMD were analyzed separately, there was no additional prognostic value from the presence or absence of SF3B1 mutations (Figures 1 and 2; p=0.67 and 0.44, respectively). Conclusions: SF3B1 mutations are prevalent in RARS and RCMD-RS but do not provide additional, WHO morphology-independent or IPSS-R-independent, prognostic information. Disclosures: No relevant conflicts of interest to declare.

Prognostic Irrelevance of Ring Sideroblast Percentage in World Health Organization Defined Myelodysplastic Syndromes without Excess Blasts,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3803-3803
Author(s):  
Mrinal M. Patnaik ◽  
Curtis A Hanson ◽  
Nanna Sulai ◽  
Janice M Hodnefield ◽  
Ryan A Knudson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Prognostic Scores ◽  
World Health ◽  
Refractory Anemia ◽  
Ring Sideroblasts ◽  
Red Cell Transfusion ◽  
Health Organization ◽  
Risk Categories

Abstract Abstract 3803 Background: Ring sideroblasts (RS) represent abnormal mitochondrial iron deposits that are commonly present in myelodysplastic syndromes (MDS). The presence of ≥15% RS, by definition (World Health Organization-WHO) is necessary for a diagnosis of a MDS-RS; with refractory anemia with ring sideroblasts (RARS) being a specific morphologic category. RS can also be seen with other morphologic categories such as; refractory cytopenias with multilineage dysplasia (RCMD), MDS-unclassifiable (MDS-U) and refractory anemia with excess blasts (RAEB-1/2). Amongst these categories, RARS is generally believed to have the best survival rate with the lowest risk of leukemic transformation and this has been attributed to the absence of associated dysplasia in more than one lineage. However, it has not been systematically shown whether or not the exact percentage of RS provides additional prognostic information in the context of an accurate morphologic categorization and risk stratification by karyotype or the revised IPSS (IPSS-R). Methods: 200 patients with primary MDS without excess blasts and ≥1% RS were seen at the Mayo Clinic from 1997 through 2007. All patients underwent bone marrow (BM) examination and cytogenetic evaluation at diagnosis and the pathology slides, including iron stains, were centrally re-reviewed to accurately quantify bone marrow (BM) RS percentage and to confirm WHO morphologic categories. Molecular profiling included analysis for IDH1, IDH2, JAK2 and MPL mutations. For the purposes of this study patients were divided into 4 categories based on the RS percentage; <5%, 5–14%, 15–50% and >50%. In addition, each patient was assigned IPSS and IPSS-R prognostic scores at diagnosis and risk stratified by karyotype according to the IPSS-R cytogenetic risk categories. Cox proportional regression method was used for multivariable analysis. Results: Of the overall 200 study patients, 140 (70%) were male and median age was 71 years (range, 17–90 years). At presentation, 34 (17%) patients were red cell transfusion-dependent. There were 56 (28%) patients with <5% RS (RCMD-52, MDS-U-14), 32 (16%) with 5–14% RS (RCMD-29, MDS-U-3), 79 (39%) with 15–50% RS (RARS-43, RCMD-29, MDS-U-2) and 33 (16%) with >50% RS (RARS-13, RCMD-17, MDS-U-3). Three patients (2%) were IDH1 mutant (RARS-1, RCMD-2), 17 (8%) IDH2 mutant (RARS-1, RCMD-14, MDS-U-2), 5 JAK2 V617F (3%) mutant (RARS-2, RCMD-3) and one patient with RCMD had the MPL W515L mutation. At a median follow-up of 33 months, 156 (73%) deaths and 24 (12%) leukemic transformations were documented. Median survivals were 63 months for MDS with >50% RS, 43 months for MDS with 15–50% RS, 35 months for MDS with 5–14% RS, and 14 months for MDS with <5% RS (p=0.005). In univariate analysis, additional risk factors included decreased hemoglobin, decreased platelet count, increased circulating blasts, WHO morphologic categories, red cell transfusion need, IPSS, IPSS-R and cytogenetic risk categories per IPSS-R. On a multivariable analysis only the IPSS-R prognostic score (p<0.0001) and the WHO morphologic categories (p=0.02 for RARS) retained significance. Univariate analysis disclosed significantly inferior leukemia-free survival (LFS) in patients with RCMD, thrombocytopenia, increased circulating blasts, and poor IPSS and IPSS-R prognostic scores. On multivariable analysis once again only the IPSS-R prognostic scores (p=0.02) and WHO morphologic categories (p=0.02) retained their significance. In other words, RS percentage, independent of WHO classification, as a continuous or categorical variable (i.e.: <5%, 5–14%, 15–50% & >50%) did not affect either overall survival or LFS. Conclusions: In MDS without excess blasts, once an accurate WHO morphologic categorization is made based on the presence or absence of multi-lineage dysplasia, there is no additional prognostic value for quantifying bone marrow ring sideroblasts. WHO classification and IPSS-R prognostic scores remain the most important factors in assessing patients with MDS. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5674-5677 ◽  
Author(s):  
Mrinal M. Patnaik ◽  
Curtis A. Hanson ◽  
Nanna H. Sulai ◽  
Janice M. Hodnefield ◽  
Ryan A. Knudson ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Multivariable Analysis ◽  
World Health ◽  
Refractory Anemia ◽  
Idh Mutations ◽  
Ring Sideroblasts ◽  
Transfusion Dependency ◽  
Health Organization ◽  
The Impact

Abstract 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.

scholarly journals World Health Organization class-independent risk categorization in mastocytosis

2019 ◽  
Vol 9 (3) ◽  
Author(s):  
Animesh Pardanani ◽  
Terra L. Lasho ◽  
Kaaren K. Reichard ◽  
Curtis A. Hanson ◽  
Ayalew Tefferi
Keyword(s):  
World Health Organization ◽  
World Health ◽  
Health Organization ◽  
Risk Categorization

PENGARUH AKSES DAN MOTIVASI TERHADAP PERILAKU IBU HAMIL DALAM MELAKUKAN KUNJUNGAN ANTENATAL DI WILAYAH KERJA PUSKESMAS PANCUR BATU TAHUN 2015

2016 ◽  
Vol 1 (2) ◽  
pp. 48-60
Author(s):  
Oktafiana Manurung ◽  
Ermawaty Arisandi Siallagan
Keyword(s):  
Antenatal Care ◽  
World Health Organization ◽  
Univariate Analysis ◽  
World Health ◽  
Bivariate Analysis ◽  
Antenatal Visit ◽  
Chi Square ◽  
Cross Sectional ◽  
The World ◽  
Health Organization

According to the World Health Organization (WHO) Indonesian women have According to the World Health Organization (WHO) Indonesian women have very bad criteria in terms of health, marriage, employment, education, equality with men. This condition is thought to lead to low maternal access to antenatal care. Goals : Antenatal care in accordance with antenatal care standards may decrease Maternal and Infant Mortality due to regular antenatal care can detect early problems that occur in the mother during pregnancy.Methods : The type of this research is analytical descriptive with cross sectional design which aims to analyze the influence of access and motivation of pregnant mother to mother behavior in doing antenatal visit. The research was conducted in Pancur Batu Puskesmas Working Area. The population is 181 people and the sample size is 61 people. Data analysis was performed using univariate analysis, bivariate analysis with Chi-Square test, and multivariate analysis with multiple logistic regression test.Result : The result of this research indicate that physical accessibility variable is the availability of unrelated officer (p = 0,461) to mother behavior in antenatal visit, social accessibility variable (p = 0,005) and attitude (p = 0,023), and for motivation variable is motive P = 0.005) and expectations (p = 0.019) had a significant effect on maternal behavior in antenatal visits.Conclution : Based on the results of research suggested Head of Pancur Batu Puskesmas to conduct training to officers especially midwives who provide services mainly about hospitality in providing services and to officers implementing services further improve the communication of information and education so that every pregnant women have a good understanding that can eventually cause attitude Positive, high motivation and expectation that can affect the mother in conducting standardized antenatal visits.

Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade II gliomas

2006 ◽  
Vol 60 (3) ◽  
pp. 380-383 ◽  
Author(s):  
Johan Pallud ◽  
Emmanuel Mandonnet ◽  
Hugues Duffau ◽  
Michèle Kujas ◽  
Rémy Guillevin ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
World Health Organization ◽  
Growth Rates ◽  
Prognostic Value ◽  
World Health ◽  
Resonance Imaging ◽  
Grade Ii ◽  
Health Organization

Retrospective Analysis of Patients with Refractory Cytopenia with Unilineage Dysplasia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4847-4847
Author(s):  
Yuchun Wang ◽  
Xin Du ◽  
Suxia Geng
Keyword(s):  
Myelodysplastic Syndromes ◽  
Who Classification ◽  
Conflicts Of Interest ◽  
Major Change ◽  
Classification Systems ◽  
World Health ◽  
Refractory Anemia ◽  
Prognostic Information ◽  
Prognostic Assessment ◽  
Health Organization

Abstract Abstract 4847 Background Myelodysplastic syndromes (MDS) are a group of clonal heterogeneous bone marrow stem cell disorders characterized by dysplastic hypercellular marrows with peripheral cytopenias. Accurate diagnosis and classification are essential for subgroup identification and prognostic assessment of patients with MDS. Classification systems such as the World Health Organization (WHO) classification are widely used but do not always provide sufficient prognostic information. So WHO improved the classification systems last year(2008). The major change was that refractory anemia (RA) was substituted by refractory cytopenia with unilineage dysplasia (RCUD). The aim of this study was to apply the new WHO classification to re-evaluate MDS with RA. Methods MDS patients with RA diagnosed between 2000 and 2008 were retrospectively reclassified with WHO criteria (2008). Results According to the new WHO classification, RCUD is intended to encompass those myelodysplastic syndromes (MDS) which present with a refractory cytopenia with unilineage dysplasia and includes refractory anemia (RA), refractory neutropenia (RN) and refractory thrombocytopenia (RT), so in 34 cases diagnosed as RA, 12 cases (12/34,35%) still pertained to RA, 19 cases (56% ) to RN and 3 (9%) cases to RT. IPSS showed 94% of RCUD cases categorized as low or intermediate-I risk. The median survival of patients with RCUD was 84 months. Conclusions RA is the main subtypes of RCUD. Understanding the clinical features of RCUD accurately is helpful to determine the right subtype of RCUD. The new WHO classification system was improved to provide better diagnostic criteria. Disclosures No relevant conflicts of interest to declare.

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