Myelodysplastic Syndrome Patients Younger Than 50 Years: Epidemiological Data and Clinical Features

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4976-4976
Author(s):  
Massimo Breccia ◽  
Paola Finsinger ◽  
Roberto Latagliata ◽  
Laura Cannella ◽  
Giuseppina Loglisci ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Clinical Features ◽  
Who Classification ◽  
Conflicts Of Interest ◽  
Low Risk ◽  
Refractory Anemia ◽  
Monosomy 7 ◽  
Younger Patients ◽  
Male Predominance

Abstract Abstract 4976 Less than 10% of patients with myelodysplastic syndromes (MDS) are younger than 50 years. It is yet unknown the exact role of prognostic scoring systems in this subset, because clinical relevant data were derived from large series of elderly patients. Undefined are also the clinical features of younger patients exposed to potential mutagens due to occupational reasons. Aim of our study was to report and analyze one of the largest series of young MDS, in terms of prognosis and overall survival. Ninety-one patients with MDS aged less than 50 years consecutively diagnosed and conservatively treated form July 1983 and December 2009 are reported and compared with the whole population of elderly MDS patients. Median age at diagnosis was 44 years (range 21–50). Sex M/F ratio was 0.68. According to FAB criteria there were 56 patients with refractory anemia (RA), 3 with refractory anemia with ringed sideroblasts (RARS), 22 with refractory anemia with excess of blasts (RAEB), 5 with refractory anemia with excess of blasts in transformation (RAEB-t) and 5 with chronic myelomonocytic leukemia (CMML). Revised 2008 WHO classification reclassified low risk patients as pure RA (only 8 patients), refractory unilineage cytopenia (RCUD, refractory thrombocytopenia, 2 patients) and refractory cytopenia with multilineage dysplasia (RCMD, 45 patients). RAEB patients were classified as RAEB-1 (11 patients) and RAEB-2 (11 patients). Eighty-five patients had evaluable cytogenetic analysis: the most frequent karyotypic change was trisomy 8 (10.5%), followed by monosomy 7 (5%). Among this cohort, 23 patients had occupational exposure to potential mutagens (more frequently benzene and its derivates and solvents): in the exposed group there was a male predominance (16/7), a higher frequency of RCMD (52%) and a higher frequency of monosomy 7 (13%). At a median follow-up of 72 months, 22 patients (24 %) evolved to acute leukemia: among the exposed cohort, a higher frequency of AML evolution was observed (39% vs 19% of non-exposed). IPSS categorization showed 30 patients as low risk, 35 patients as intermediate-1, 14 patients as intermediate-2 and 4 patients as high risk, with intermediate-1 risk being the more commonly detected. Both the intermediate-2 and high risk according to IPSS, together with age cut-off above 40 years, male sex, FAB and WHO high-risk definition and exposure to carcinogens during lifetime, were found to be predictive of a shorter overall survival. Comparison of younger patients with elderly MDS population followed in the same Institute over the same period of time, showed statistical differences in survival (88 months for younger vs 24 months for elderly MDS, p<0.0001), sex ratio (p=0.002), FAB and WHO classification (both p=0.03). These results suggest that MDS in patients aged less than 50 years could be identified as a distinct category and that aggressive approaches should rarely be recommended for younger patients belonging to the low and intermediate-I risk groups. Disclosures: No relevant conflicts of interest to declare.

Myelodysplastic Syndromes in Adults - Preliminary Results From the First, Retrospective, Multicenter Brazilian Registry.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4841-4841
Author(s):  
Silvia M.M. Magalhães ◽  
Rosane Bittencourt ◽  
Elvira Velloso ◽  
Maria de Lourdes Chauffaille ◽  
Alita Andrade Azevedo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Clinical Features ◽  
Myelodysplastic Syndromes ◽  
Tertiary Care ◽  
Incidence Rates ◽  
Low Risk ◽  
Refractory Anemia ◽  
Survival Curves ◽  
Fab Classification

Abstract Abstract 4841 Myelodysplastic syndromes (MDS) are a group of acquired clonal stem cell disorders that mainly affect the elderly population, characterized by ineffective hematopoiesis and high risk of leukemic transformation. MDS are heterogeneous in terms of morphology, clinical features and survival. An increasing body of work reveals that there might be differences in clinical features between Asian and Western cases. Japanese patients seem to be younger, have a lower frequency of refractory anemia (RA) with ringed sideroblast (RARS) and a higher frequency of RA, according to FAB classification, as well as different prognostic factors such as the frequency of cytogenetic abnormalities. Incidence rates for MDS in Brazil are unavailable. The purpose of the study was to obtain epidemiological data of MDS adult patients who presented from January 2003 to December 2007 in 10 Brazilian tertiary-care hematology centers from different regions of the country. Patient data collected by participating physicians were entered and stored with the use of an internet-based, data collection tool. Blood counts, bone marrow aspiration, trephine biopsy and chromosomal study were recorded. Survival was estimated through Kaplan-Meier method and the difference between survival curves was assessed by means of Log-Rank Test. Death incidence rates were estimated and compared. Statistical analyses of relevant variables were performed. Three hundred and forty three patients with diagnosis of MDS according to FAB/WHO classification were included in this retrospective analysis. The mean age at presentation was 68 years (range 17 to 98). Fifty percent of cases were male. Cigarette smoking, alcohol abuse and pesticide/herbicide exposure were reported in 33.5%, 13.4% and 14.3% respectively. Median hemoglobin was 8.7 g/dL, median neutrophils count was 1,575/mm3 and median platelets count was 97,000/mm3. There was no excess of blasts in 68.4% of cases. Bone marrow biopsy was performed in 78.5% of patients. Lymphoid nodules were seen in 11.3% and any degree of fibrosis in 28.6%. Cytogenetic analysis was performed in 67.8% of cases and showed chromosomal abnormalities in 50.5%. The del(5q) isolated or combined with other alterations were observed in 6.0%. Flow cytometry analysis for CD55 and CD59 was performed in 11,3% and was normal in 97,4%. Near 8% of cases were classified as secondary MDS. The distribution of disease subtypes according to FAB classification was: RA 42,3%, RARS 9,0%, RA with excess of blasts (RAEB) 20,7%, RAEB-t 4,2% and chronic myelomonocytic leukemia (CMML) 3,9%. According to IPSS patients were stratified as low-risk (low risk plus intermediate I) 55,9% and high risk (intermediate II and high risk) 13,1%. In 30,1% no stratification was possible. In 26,5% of cases iron overload was diagnosed although only 28,3% of cases had performed serum ferritin. The follow-up time ranged from 1 to 78 months (mean: 28 months). Thirty-six percent of patients died and the death was MDS-related in 68.3% of cases. The high and low risk survival curves were significantly different (p<0,001), and, the death incidence rate (per 1000 person.month) was 8,7 (95% CI: 6,6-11,4) and 29,1 (95% CI: 19,5-43,4) for the low and high-risk group respectively. This clinical registry of adult Brazilian MDS patients represents a unique opportunity to gain insight about these disorders and its demographic and clinical features and provide an important baseline for future studies. Disclosures No relevant conflicts of interest to declare.

Factors Involved in Response to Thalidomide in Myelodysplastic Syndrome: Impace of HLA and Prognostic Factors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5079-5079
Author(s):  
Sule Mine Bakanay ◽  
Klara Dalva ◽  
Pervin Topcuoglu ◽  
Sinem Civriz-Bozdag ◽  
Mutlu Arat ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Dose Range ◽  
Response Rates ◽  
Risk Groups ◽  
Low Risk ◽  
Refractory Anemia ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Significant Difference

Abstract Myelodysplastic Syndrome (MDS) is a clonal disease of hematopoiesis characterized by dysplasia in one or more lineages. Since the syndrome is clinically heterogenous, treatment options are complex and hard to define. Thalidomide (T) is the first agent tested in MDS for its immunomodulatory and anti-angiogenic effects. Twenty to 59 % response rates, which is mainly hematological improvement, have been reported. However, because of excessive toxicity and low response rates, thalidomide has not been widely used as an effective treatment option for MDS. Factors invoved in response to T are not well delineated. Better response to immunosupression (IS) in HLA-DRB1*15(+) patients with aplastic anemia and some MDS subgroups have been reported. In this study, the medical records of MDS patients, who received T at least for ≥ 3 months were retrospectively analyzed. Responses could be evaluated in 47 patients with a median age of 59 years (range, 15–84) and M/F: 29/18. According to WHO classification, there were 7 refractory anemia (RA), 9 refractory anemia with ring sideroblasts (RARS), 5 refractory cytopenia with multilineage dysplasia (RCMD), 2 RCMD-RA, 13 RCMD-RS, 6 Hypoplastic MDS, 1 RAEB, 4 MDS/MF. International Prognostic Scoring (IPSS) risk groups consisted of 42 low/intermediate-1 and 5 intermediate-2/high risk patients. Clonal cytogenetic abnormalities were found in 16 patients (5 trisomy 8, 3 monosomy 7, 2 delY, 2 increased chromosomal breaks, 1 del5q, 1 monosomy 15 and 1 del21q). Thalidomide was administered at a dose range of 100–400mg/day and for a range of 3–48 months. Twenty-one patients had hematological response (10 major and 11 minor). Seven patients among responders had received additional erythropoietin (EPO) combined with T. There was no statistically significant difference between responders and non-responders in terms of age (median 53 vs 60.5 years), sex (M/F: 12/9 vs 17/26) and IPSS risk groups (Low risk/high risk: 19/2 vs 23/3). Response rates were 44% in RA; 50% in RCMD-RA; 56% in RARS; 55% in RCMD-RS; 20% in RCMD; 20% in hypoplastic MDS; 75% in MDS/MF. and none in RAEB patient. The EPO levels did not differ significantly between the responders and non-responders (EPO miu/ml &lt;500 in 93% vs 83%). However, compared with non-responders, majority of the responders had ferritin levels &lt;1000 mcg/L (83% vs 50%, p&lt;0.05). A total of 21 patients had their HLA type screened. HLADRB1*15 was detected in 44% of responders (4/9) and 16% of non-responders (2/12) (p&lt;0.05). Interestingly, among 5 patients who had trisomy 8, 4 responded to T. Fourty-five percent of mainly low risk-MDS patients responded to T. Patients with MDS/MF and RARS/RCMD-RS and patients with less iron overload responded better. HLADRB1*15 predominance and the presence of trisomy 8 in T responders should be underlined.

Epidemiological and Clinicopathological Data From the Brazilian Registry of Patients with Myelodysplastic Syndromes and Comparative Analysis Between Different Geographic Areas

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1884-1884 ◽  
Author(s):  
Silvia M. M. Magalhaes ◽  
Tania Silva Madeira ◽  
Rosane Bittencourt ◽  
Elvira Velloso ◽  
Maria de Lourdes Chauffaille ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Features ◽  
Myelodysplastic Syndromes ◽  
Conflicts Of Interest ◽  
Geographical Area ◽  
Clinicopathological Features ◽  
Patterns Of Care ◽  
Refractory Anemia ◽  
Clinical Expertise ◽  
Significant Difference

Abstract Abstract 1884 Brazil is a country of continental dimensions, divided into five regions with ethnic, economical and social heterogeneity. The country is experiencing a rapid and intense demographic transition. Those aged 60 and over represent 10.5%, the fastest growing age group in the population. Myelodysplastic syndromes (MDS) have been reported to differ regarding clinical features, subtype distribution, frequency of abnormal karyotypes and overall survival between Western and Eastern countries, suggesting that ethnic and environmental differences may play a role. This study is a multicenter observational cross-sectional registry. The primary objective was to characterize demographics, clinicopathological features and patterns of care of patients with MDS treated in 12 Brazilian tertiary centers, selected based on clinical expertise and scientific experience. Four hundred and seventy-six patients with date of diagnosis between January/2003 and December/2007 were considered in the analysis: 50.8% were female, the median age at time of diagnosis was 68.3 years, with lower figure in Southern region: 65 years (p=0.02); 86.6% lived in urban area and rural origin was higher in Northeast (p<0.001). Median Hb at presentation was 8g/dL, neutrophils 1,575/mm3 and platelets 97,000/mm3. No difference in severity of cytopenias was observed between regions. Dyserythropoiesis was the most prevalent abnormality (82%). A biopsy was performed in 74.1% of cases. Any degree of fibrosis was detected in 19.5%. Lower median estimated cellularity (50%) (p=0.001) and higher percentage of fibrosis (p=0.01) was observed in Northeast. Most patients performed cytogenetics (62.4%) and a protocol to exclude non-clonal disorders. Ferritin was analyzed in only 24.6% of cases and median value was 483ng/dL. Most patients had primary MDS (92.9%) and low-risk IPSS (83.2%). The predominant subtype was refractory anemia (56.7%) according to FAB and refractory cytopenia with multilineage dysplasia (40.6%) according to WHO classification. Red cell transfusion dependency was recorded in 66.3%, the majority received ≥20 units and iron overload was diagnosed in only 21% of cases. Referring to treatment, any growth factor was used in 44.2%, thalidomide in 16.1%, immunosuppressive therapy in 9.4% and iron chelation in only 6.4%. Allogenic bone marrow transplantation was reported in 3.4% of cases. Although pattern of supportive care did not differ between regions a significant difference was observed in median overall survival (p=0.002). Median time of follow-up was 31m. The Brazilian registry of MDS patients represents a unique opportunity to characterize demographic and clinicopathological features and patterns of care and to compare data from the different regions and from different countries. Some clinical features are similar to Eastern countries, supporting the speculation that different, adapted clinical guidelines would be required. Regional differences may be due to ethnic and racial characteristics secondary to different patterns of migration in a large geographical area, suggesting that genetic as well as environmental factors may play a role. Disclosures: No relevant conflicts of interest to declare.

Azacitidine for Treatment of Therapy Related Myelodysplastic Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1712-1712
Author(s):  
Rami S. Komrokji ◽  
Najla H Al Ali ◽  
E Alrawi ◽  
Eric Padron ◽  
Janelle Perkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Scoring System ◽  
Research Funding ◽  
Who Classification ◽  
De Novo ◽  
Risk Groups ◽  
Refractory Anemia ◽  
Cancer Center ◽  
P Value

Abstract Abstract 1712 Background: Therapy related MDS (t-MDS) is a rising challenge, it accounts for about 10%-15% of MDS cases. Outcome of t-MDS is generally poor. Azacitidine is currently standard of care for higher risk MDS based on AZA-001 randomized clinical trial demonstrating survival advantage. Efficacy of azacitidine in t-MDS is not well studied. We investigated the outcome of t-MDS patients treated with azacitidine at the Moffitt Cancer Center (MCC). Methods: This was a retrospective review of t-MDS cases treated at Moffitt Cancer Center (MCC) with azacitidine. Patients were identified through MCC MDS database and individual charts were reviewed. The primary objective was overall survival (OS) from time of azacitidine starting date. Patients were included if at least received one cycle of azacitidine. Disease status was defined by both the French American British (FAB) and the World Health Organization (WHO) classification systems, and risk was scored by the International Prognostic Scoring System (IPSS), and MD Anderson Scoring System (MDAS). Response to azacitidine was defined per the International Working Group (IWG 2006) criteria. All analyses were conducted using SPSS version 15.0. (SPSS Inc, Chicago, IL). Descriptive statistics were used for baseline characteristics and responses. Kaplan-Meier estimates were used to calculate overall survival (OS). Results: Between July 2004 and April 2010, 76 patients with t-MDS/AML were treated with azacitidine. The median duration of follow up was 58 months. The median age was 64.5 years (36–84). Majority of patients were Caucasians race 87% (n=66) and 55% (n=42) were male gender. The underlying malignancy was hematological malignancy in 38 patients (50%), solid tumor in 34 patients (45%), and 4 patients (5%) had both. Prior treatment for primary malignancy included chemotherapy in 44 patients (58%), chemoradiation in 23 patients (30%), and 9 patients (12%) received radiation therapy only. Fourteen patients received prior autologous SCT. According to WHO classification 2.6% (2) were Refractory anemia (RA), 3.9% (3) Refractory anemia with ring sideroblasts (RARS), 30.3% (23) refractory anemia with multilineage cytopenia (RCMD), 28.9% (22) refractory anemia with excess blasts I (RAEB-I), 25% (19) refractory anemia with excess blasts II (RAEB-II), 1.3% (1) CMML, 6.6% (5) AML, and 1.3 % (1) unknown. The IPSS risk was low in 1.3% (1), intermediate-1 (int-1) 19.7% (15), int-2 57.9% (44), high risk 17.1% (13) and unknown 3.9% (3). Based on MDAS the risk groups were 1.3% (1) low, 7.9% (6) int-1, 26.3% (20) int-2, 63.2% (48) high risk, and 1.3% (1) unknown. The cytogenetic risk groups were in 13.2% (10) good, 10.5% (8) intermediate, 72.4% (55) poor, and 1.3% (1) unknown. The median number of azacitidine cycles was 4 (Range 1–18). The response rates (IWG 2006 criteria) were 11.8% (9) CR, 2.6% (2) marrow CR, 10.5% (8) PR, 18.4% (14) HI, 14.5% (11) Stable disease (SD), 21.1 % (16) progressive disease (PD), and 17.1% (13) unknown. The overall response rate (CR+mCR+PR+HI) was 43.4 % (33). Among all patients 34.2% (26) had HI-E, 23.7% (18) had HI-N, and 32.9% (25) HI-P. The median OS was 14.9 months (95%CI 12.2–17.7) from start of azacitidine treatment. Twenty patients underwent allogeneic stem cell transplant (allo SCT). The median OS survival for patients who underwent allo SCT was 22.2 months compared to 13.6 months for those who did not. (p-value 0.015, log rank test). The median OS for patients who achieved SD or better best response with azacitidine therapy was 17.2 months compared to 8.3 months for patients with PD (p-value 0.014). Conclusion: Azacitidine is active in t-MDS; response rates are comparable to de novo MDS patients. Overall survival for t-MDS treated with azacitidine is slightly inferior to de novo MDS treated on AZA-001 study in general but similar to those with poor karyotype on the same study. Disclosures: Komrokji: Celgene: Honoraria, Research Funding, Speakers Bureau. Lancet:Celgene: Research Funding. List:Celgene: Consultancy.

scholarly journals A prognostic model based on seven immune-related genes predicts the overall survival of patients with hepatocellular carcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qian Yan ◽  
Wenjiang Zheng ◽  
Boqing Wang ◽  
Baoqian Ye ◽  
Huiyan Luo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Risk Score ◽  
Immune Cells ◽  
Prognostic Model ◽  
Risk Groups ◽  
Low Risk ◽  
Prognostic Performance ◽  
Immune Related Genes

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.

scholarly journals Impact of Different Modules of 21-Gene Assay in Early Breast Cancer Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengdi Chen ◽  
Deyue Liu ◽  
Weilin Chen ◽  
Weiguo Chen ◽  
Kunwei Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Younger Patients ◽  
Gene Assay ◽  
Risk Patients ◽  
Gene Modules ◽  
The Impact

BackgroundThe 21-gene assay recurrence score (RS) provides additional information on recurrence risk of breast cancer patients and prediction of chemotherapy benefit. Previous studies that examined the contribution of the individual genes and gene modules of RS were conducted mostly in postmenopausal patients. We aimed to evaluate the gene modules of RS in patients of different ages.MethodsA total of 1,078 estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients diagnosed between January 2009 and March 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were included. All patients were divided into three subgroups: Group A, ≤40 years and premenopausal (n = 97); Group B, &gt;40 years and premenopausal (n = 284); Group C, postmenopausal (n = 697). The estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of the variance tests were conducted for RS and its constituent modules.ResultsIn patients &gt;40 years, RS had a strong negative correlation with its estrogen module (ρ = −0.76 and −0.79 in Groups B and C) and a weak positive correlation with its invasion module (ρ = 0.29 and 0.25 in Groups B and C). The proliferation module mostly contributed to the variance in young patients (37.3%) while the ER module contributed most in old patients (54.1% and 53.4% in Groups B and C). In the genetic high-risk (RS &gt;25) group, the proliferation module was the leading driver in all patients (ρ = 0.38, 0.53, and 0.52 in Groups A, B, and C) while the estrogen module had a weaker correlation with RS. The impact of ER module on RS was stronger in clinical low-risk patients while the effect of the proliferation module was stronger in clinical high-risk patients. The association between the RS and estrogen module was weaker among younger patients, especially in genetic low-risk patients.ConclusionsRS was primarily driven by the estrogen module regardless of age, but the proliferation module had a stronger impact on RS in younger patients. The impact of modules varied in patients with different genetic and clinical risks.

scholarly journals Mutational Characteristics and Changing Pattern from Idiopathic Cytopenia of Undetermined Significance to High-Risk Myelodysplastic Syndrome Stratified By IPSS-R

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3009-3009
Author(s):  
Eun-Ji Choi ◽  
Young-Uk Cho ◽  
Seongsoo Jang ◽  
Chan-jeoung Park ◽  
Han-Seung Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Rna Splicing ◽  
Conflicts Of Interest ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
Sequencing Data ◽  
Undetermined Significance

Background: Unexplained cytopenia comprises a spectrum of hematological diseases from idiopathic cytopenia of undetermined significance (ICUS) to myelodysplastic syndrome (MDS). Revised International Prognostic Scoring System (IPSS-R) is the standard tool to assess risk in MDS. Here, we investigated the occurrence, characteristics, and changing pattern of mutations in patients with ICUS and MDS stratified by IPSS-R score. Methods: A total of 211 patients were enrolled: 73 with ICUS and 138 with MDS. We analyzed the sequencing data of a targeted gene panel assay covering 141 genes using the MiSeqDx platform (Illumina). The lower limit of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Bone marrow components were assessed for the revised diagnosis according to the 2016 WHO classification. Lower-risk (LR) MDS was defined as those cases with very low- or low-risk MDS according to the IPSS-R. Higher-risk (HR) MDS was defined as those cases with high- or very high-risk MDS according to the IPSS-R. Results: Patients with ICUS were classified as very low-risk (39.7%), low-risk (54.8%), and intermediate-risk (5.5%) according to the IPSS-R. Patients with MDS were classified as LR (35.5%), intermediate-risk (30.4%), and HR (34.1%). In the ICUS, 28 (38.4%) patients carried at least one mutation in the recurrently mutated genes in MDS (MDS mutation). The most commonly mutated genes were DNMT3A (11.0%), followed by TET2 (9.6%), BCOR (4.1%), and U2AF1, SRSF2, IDH1 and ETV6 (2.7% for each). IPSS-R classification was not associated with mutational VAF and the number of mutations in ICUS. In the 49 LR MDS, 28 (57.1%) patients carried at least one MDS mutation. The most commonly mutated genes were SF3B1 (20.4%), followed by TET2 (12.2%), U2AF1 (10.2%), DNMT3A (10.2%), ASXL1 (10.2%), and BCOR (6.1%). Higher VAF and number of mutations were observed in LR MDS compared to ICUS patients. In the 42 intermediate-risk MDS, 27 (64.3%) patients carried at least one MDS mutation. The most commonly mutated genes were ASXL1 (23.8%), followed by TET2 (21.4%), RUNX1 (16.7%), U2AF1 (14.3%), DNMT3A (14.3%), SF3B1 (9.5%), and SRSF2, BCOR, STAG2 and CBL (7.1% for each). In the 47 HR MDS, 36 (76.6%) patients carried at least one MDS mutation. The most commonly mutated genes were TET2 (25.5%), followed by DNMT3A (14.9%), TP53 (14.9%), RUNX1 (12.8%), U2AF1 (10.6%), ASXL1 (10.6%), and SRSF2 and KRAS (6.4% for each). As the disease progressed, VAF and number of the MDS mutations gradually increased, and mutations involving RNA splicing, histone modification, transcription factor or p53 pathway had a trend for increasing frequency. Specifically, ASXL1, TP53, and RUNX1 mutations were the most striking features in patients with advanced stage of the disease. Cohesin mutations were not detected in ICUS, whereas these mutations were detected at a relatively high frequency in HR MDS. Our data were summarized in Table 1. Conclusions: We demonstrate that on disease progression, MDS mutations are increased in number as well as are expanded in size. Furthermore, a subset of mutations tends to be enriched for intermediate- to HR MDS. The results of this study can aid both diagnostic and prognostic stratification in patients with unexpected cytopenia. In particular, characterization of MDS mutations can be useful in refining bone marrow diagnosis in challenging situations such as distinguishing LR MDS from ICUS. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma

2020 ◽  
Author(s):  
Yi Ding ◽  
Tian Li ◽  
Min Li ◽  
Tuersong Tayier ◽  
MeiLin Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Model ◽  
Risk Group ◽  
Clinical Information ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Positive Regulation ◽  
Risk Patients ◽  
Cox Analysis

Abstract Background: Autophagy and long non-coding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.Methods: We downloaded RNA-sequencing data and clinical information of melanoma from The Cancer Genome Atlas. The co-expression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate COX regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.Results: According to the results of the univariate COX analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate COX analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p<0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNAs risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Risk Classification ◽  
Low Risk ◽  
Classification Model ◽  
Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

scholarly journals Risk stratification in pediatric low-grade glioma and glioneuronal tumor treated with radiation therapy: an integrated clinicopathologic and molecular analysis

2020 ◽  
Vol 22 (8) ◽  
pp. 1203-1213 ◽  
Author(s):  
Sahaja Acharya ◽  
Jo-Fen Liu ◽  
Ruth G Tatevossian ◽  
Jason Chiang ◽  
Ibrahim Qaddoumi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Groups ◽  
Low Risk ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Prognostic Features

Abstract Background Management of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these findings in an external dataset. Methods Children with non-metastatic, biopsy-proven unresectable LGG/LGGNT treated with RT at a single institution between 1997 and 2017 were identified. Recursive partitioning analysis (RPA) was used to stratify patients into low- and high-risk prognostic groups based on overall survival (OS). CNS9702 data were used for validation. Results One hundred and fifty patients met inclusion criteria. Median follow-up was 11.4 years. RPA yielded low- and high-risk groups with 10-year OS of 95.6% versus 76.4% (95% CI: 88.7%–98.4% vs 59.3%–87.1%, P = 0.003), respectively. These risk groups were validated using CNS9702 dataset (n = 48) (4-year OS: low-risk vs high-risk: 100% vs 64%, P &lt; 0.001). High-risk tumors included diffuse astrocytoma or location within thalamus/midbrain. Low-risk tumors included pilocytic astrocytoma/ganglioglioma located outside of the thalamus/midbrain. In the subgroup with known BRAF status (n = 49), risk stratification remained prognostic independently of BRAF alteration (V600E or fusion). Within the high-risk group, delayed RT, defined as RT after at least one line of chemotherapy, was associated with a further decrement in overall survival (P = 0.021). Conclusion A high-risk subgroup of patients, defined by diffuse astrocytoma histology or midbrain/thalamus tumor location, have suboptimal long-term survival and might benefit from timely use of RT. These results require validation.

Sign in / Sign up

Export Citation Format

Share Document