Role Of Hypomethylating Agents For Patients With Lower-Risk Myelodysplastic Syndrome Defined By IPSS and IPSS-R

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2782-2782
Author(s):  
Joon Ho Moon ◽  
Sang Kyun Sohn ◽  
Jae Sook Ahn ◽  
Yeo-Kyeoung Kim ◽  
Hyeoung Joon Kim ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Lower Risk ◽  
Conflicts Of Interest ◽  
Risk Groups ◽  
International Prognostic Scoring System ◽  
Hypomethylating Agents ◽  
Risk Patients ◽  
Very High ◽  
Prognostic Power

Abstract Background International Prognostic Scoring System (IPSS) is commonly used to distinguish various subgroups of myelodysplastic syndrome (MDS) patients with different prognosis and to make a therapeutic decision. However, the classic IPSS, defining lower-risk as low and intermediate-1 IPSS, seems to be insufficient to discriminate the prognostic groups of lower-risk MDS. Recently, IPSS was updated into the revised score (IPSS-R) to refine the IPSS by reassessing the major predictive features of MDS. The hypomethylating agents (HMA) are usually recommended for patients with lower-risk MDS who is not responsive to other therapies. However the role of HMA for the patients with lower-risk IPSS are still on debate. This study was conducted to find the rationale to treat HMA for the patients with lower-risk IPSS and to know whether IPSS-R further discriminate the prognosis of patients treated with HMA. Methods The data of 334 patients diagnosed with MDS lower-risk defined by IPSS after Jan 2006 were retrospectively reviewed. Lower-risk IPSS was revised into IPSS-R to know whether it could further discriminate the prognosis of this group of patients. The prognosis of lower-risk by IPSS and IPSS-R were analyzed in terms of overall survival (OS) and prognostic power was calculated with time-dependent Cox-hazard models. To define the role of HMA for patients with lower-risk IPSS, we categorized the lower risk patients into No-HMA group, early HMA group (HMA within 2 mo.), and late HMA group (HMA after 2 mo). Results Out of 334 lower-risk patients (39 low and 295 intermediate-1), 195 patients (58.4%) were treated with HMA (azacitidine 163, decitabine 32). Median time to HMA treatment was 43 days (range 0-1778 days). 3yr-OS rate was not significantly different between HMA group (43.1¡¾4.2%) and non-HMA group (62.3¡¾5.9%) (p=0.099). Early HMA treatment (3yr-OS 36.4¡¾5.4%) didn't show survival benefits compared to late HMA group (54.6¡¾6.3%) or no-HMA group (62.3¡¾5.9%) (p=0.003). Plus, HMA response (CR/PR/HI) didn't guarantee OS benefits: 3yr-OS of 45.2¡¾7.4% in responders (CR/PR/HI, n=74) and 43.4¡¾5.0 in non-responders (SD/PD, n=121) (p=0.239). Among 39 patients with IPSS low, 11 patients (28.2%) were revised into IPSS-R very low, 24 (61.5%) into low, 3 (7.7%) into intermediate, and 1 (2.6%) into high. Among 295 patients with IPSS intermediate-1, 4 patients (1.4%) were revised into IPSS-R very low, 84 (28.5%) into low, 133 (45.1%) into intermediate, 71 (24.1%) into high and 3 (1.0%) into very high. IPSS-R could further discriminate the IPSS lower-risk patients with regard to OS: 3yr-OS rates of 100% in very low, 64.5¡¾5.9% in low, 46.1¡¾5.5% in intermediate, 26.1¡¾6.6% in high, and 0% in very high (p<0.001). The survival benefits of HMA for lower risk groups (very low and low) defined by IPSS-R (n=123) was not defined in the current study, where 3yr-OS was 83.8¡¾6.4% in no-HMA group (n=60) vs. 60.5¡¾7.1% in HMA group (n=63) (p=0.198). Conclusion The prognosis of the patients with lower-risk IPSS (low and intermediate-1) were successfully refined by IPSS-R. The IPSS intermediate-1 risk was heterogeneous group, which subdivided into very low to very high by IPSS-R. However, the beneficial effect of HMA for patients with lower-risk MDS, defined by IPSS (low and intermedite-1) and IPSS-R (very low and low), should be elucidated in the future studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals microRNA-22 and TET-2 Mutation in Myelodysplastic Syndrome Patients Treated with Hypomethylating Agents

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5127-5127
Author(s):  
Seong Kyu Park ◽  
Se Hyung Kim ◽  
Sung Hee Lim ◽  
Chan Kyu Kim ◽  
Jong-Ho Won ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Lower Risk ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
Hypomethylating Agents ◽  
Poor Survival ◽  
Leukemic Transformation ◽  
Clinical Role ◽  
Aberrant Expression ◽  
Tet2 Mutation

Abstract Background: MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. Some reports suggested that aberrations in the miR-22-TET2 regulatory network are common in myelodysplastic syndrome (MDS) and leukemia, and its aberrant expression correlates with poor survival. We attempted to identify the clinical role of miR-22 and TET-2 in patients with myelodysplastic syndrome. Materials and Methods: A total of 41 MDS patients who treated with hypomethylating agents were recruited. Real time RT-PCR was performed to assess the expression levels of miR-22 and TET-2 mutation in bone marrow samples at the time of diagnosis. And we investigated the relationship between its results and clinical outcomes. Results: TET2 mutation frequency in the higher risk group based the IPSS and IPSS-R was lower than that of lower risk group (11.1% vs 38.1%). miR22 expression was also down-regulated in higher risk group (higher risk: 1.70 ± 0.96 vs lower risk: 3.14 ± 1.38, p=0.006). TET2 mutation seemed to be different according to the responsiveness to hypomethylating agents. TET2 mutation, IPSS, and IPSS-R were significantly associated with the risk of leukemic transformation. Patients with an decreased value in the consecutive assessment of miR-22 at the time of diagnosis and 3 months after initial treatment tended to be associated with poor survival outcome (survival rate at 3 years: 18.2% vs 35.1% for patients with an increase, p=0.168). Prognostic factors for survival included TET-2 mutation, cytogenetics, IPSS or IPSS-R, and leukemic transformation. Conclusion: miR-22 expression and TET2 mutation had a clinical impact on outcomes in MDS patients treated with hypomethylating agents. And these biomarkers might have a potential as a prognostic factor for MDS patients. Disclosures No relevant conflicts of interest to declare.

Outcome of Patients with Lower-Risk Myelodysplastic Syndrome (MDS) After Azacitidine (AZA) Treatment Failure.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2815-2815
Author(s):  
Asmita Mishra ◽  
Jeffrey E Lancet ◽  
Najla H Al Ali ◽  
Eric Padron ◽  
Viet Q. Ho ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Treatment Failure ◽  
Lower Risk ◽  
Median Overall Survival ◽  
Unmet Need ◽  
Risk Groups ◽  
Low Risk ◽  
Risk Patients

Abstract Abstract 2815 Background: Azacitidine has emerged as the standard of care for treatment of higher risk MDS based upon results of the AZA-001 study. Several groups reported poor outcomes after AZA failure in patients with int-2 or high risk International Prognostic Scoring System (IPSS) risk groups with a median overall survival (OS) ranging from 4–8 months (mo). In the USA, AZA is approved for all FAB types and risk groups and is as first or second line therapy for anemia after erythroid stimulating agents in low /int-1 risk non-deletion 5q MDS and is the treatment of choice for thrombocytopenia. The outcome of patients with lower risk myelodysplastic syndrome (MDS) after AZA failure has not been characterized. We report our experience in a large cohort of low/int-1 (lower risk) MDS patients after AZA failure. Methods: Patients were identified through the Moffitt Cancer Center (MCC) MDS database. Individual charts were reviewed and relevant clinical data was extracted. Patients with low or intermediate-1 (int-1) risk disease as defined by IPSS who had received AZA treatment were identified. These patients were also risk stratified based on Global MD Anderson Score (MDAS). The primary objective was to estimate OS in these patients after AZA failure. AZA failure was defined as failure to respond after 4 or more treatment courses, loss of response, or disease progression while on therapy. All responses were defined according to the International Working Group (IWG) 2006 criteria. The Kaplan–Meier method was used to estimate median overall survival. Results: Two hundred eighty MDS patients with low/int-1 IPSS risk who had received AZA treatment were identified. Most patients (81%) were greater than 60 years of age (median, 69 years), and 90% of AZA treated patients were RBC transfusion dependent. Refractory cytopenia with multilineage dysplasia (RCMD) was the most common WHO subtype (44%), and 81% of patients had good risk cytogenetics (Table-1). The median time from MDS diagnosis to AZA treatment was 12.3 months; median number of AZA cycles received was six. At the time of AZA treatment, 241 patients (86 %) were risk stratified as int-1 versus 39 patients (14 %) who were stratified as low risk IPSS. The IWG 2006 responses to AZA treatment included 4% CR (n=10 ), 1% marrow CR (n=2), 4% PR (n=10), 27% Hematological improvement (HI) (n=75), whereas 52% (n=146) had stable disease with no HI (n=146) and 10% had progressive disease (n=10); 6 patients (2%) died on therapy, and responses were missing in 2 patients (<1%). The overall best response (HI or better) was 36%. The median OS for the entire cohort after AZA failure was 18.5 months (95% CI [13.5–23.5 mo], Figure 1A). The median OS for patients with low risk IPSS disease from time of AZA failure was 46 months versus 15 mo for int-1 patients (p<0.005, Figure 1B). When utilizing MDAS, median OS was 33.3 months for low risk patients, 21 months for int-1, 11 months for int-2, and 7.5 months for poor risk patients (p=0.005). Conclusions: To our knowledge this is the first report describing the outcome of lower risk MDS patients after AZA treatment failure. Outcome is particularly poor for those patients with int-1 risk MDS, with a median OS of 15 mo. Global MDAS identified patients upstaged to int-2 or high risk with less than one year OS. There is unmet need for effective novel therapies for lower risk MDS patients after AZA failure. Disclosures: List: Celgene: Consultancy. Komrokji:Celgene: Speakers Bureau.

Response to hypomethylating agents improves long-term outcomes for lower-risk patients with myelodysplastic syndrome in case-matched cohorts

2018 ◽  
Vol 97 (12) ◽  
pp. 2309-2317 ◽  
Author(s):  
Dong Won Baek ◽  
Yoo Jin Lee ◽  
Hyunjeong Kim ◽  
Seo Yeon Ahn ◽  
Jae Sook Ahn ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Lower Risk ◽  
Hypomethylating Agents ◽  
Long Term Outcomes ◽  
Risk Patients

How we treat lower-risk myelodysplastic syndromes

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4280-4286 ◽  
Author(s):  
Pierre Fenaux ◽  
Lionel Adès
Keyword(s):  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Iron Chelation ◽  
International Prognostic Scoring System ◽  
Hypomethylating Agents ◽  
First Line ◽  
Thrombopoietin Receptor ◽  
Red Blood Cell Transfusions

AbstractLower-risk myelodysplastic syndromes (MDSs) are defined as having low or intermediate 1 risk by the International Prognostic Scoring System and are characterized mainly by anemia in most cases. Supportive care—primarily red blood cell transfusions—remains an important component of their treatment, but exposes patients to insufficient correction of anemia, alloimmunization, and organ iron overload (for which the role of iron chelation remains debated). Treatment aimed at preventing anemia recurrence should therefore be used whenever possible. Erythropoiesis stimulating agents remain the first-line treatment of anemia in most lower-risk MDS without del(5q), whereas anemia of low-risk MDS with del 5q responds to lenalidomide in two-thirds of the cases, but this drug should be used cautiously because profound cytopenias may occur initially. Treatment after failure of those first-line therapies are disappointing overall, with many patients eventually requiring long-term transfusions, but encouraging results have been reported with hypomethylating agents and lenalidomide. Selected patients respond to antithymocyte globulins, and thrombopoietin receptor agonists are under investigation in lower-risk MDS with thrombocytopenia. Some patients, while remaining at a “lower risk” MDS level, have severe cytopenias and/or poor prognostic factors, found using newer prognostic parameters, or resistance to treatment, making them urgent candidates for more intensive approaches, including allogeneic stem cell transplantation.

Survival Advantage with Hypomethylating Agents In Patients with Higher Risk Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1859-1859
Author(s):  
Young-Hoon Park ◽  
Je-Hwan Lee ◽  
Kyoo Hyung Lee ◽  
Jung-Hee Lee ◽  
Dae-Young Kim ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Survival Data ◽  
Lower Risk ◽  
Conflicts Of Interest ◽  
Cox Model ◽  
Immunosuppressive Treatment ◽  
Complete Response ◽  
Risk Category ◽  
Hypomethylating Agents ◽  
Treatment Groups

Abstract Abstract 1859 Background: Two hypomethylating agents, azacitidine and decitabine, are active in myelodysplastic syndrome (MDS) and both drugs have been approved for the treatment of MDS in Korea. In this retrospective analysis, we tried to analyze the effects of hypomethylating agents on the clinical outcomes of the patients with MDS. Methods: A total of 385 patients, who were diagnosed as MDS at the Asan Medical Center between July 1992 and March 2010, were included in this study. We divided the patients into three treatment groups such as hypomethylating therapy (HMT, n=92), intensive chemotherapy (IC, n=15), and supportive care (including low-dose cytarabine and immunosuppressive treatment, SC, n=278). Primary end points of this study were overall survival (OS) and progression-free survival (PFS). PFS was defined as time from diagnosis to AML progression or death. All survival data were censored at the time of hematopoietic cell transplantation (HCT) to eliminate the influence of HCT on survivals. The difference of survivals was compared using time updated Cox model because times from diagnosis of MDS to treatment (HMT or IC) were various. Results: Baseline clinico-laboratory features were not significantly different between 3 treatment groups (HMT vs. IC vs. SC) in regard to sex, age, WHO subtype, and IPSS risk category. Among 83 patients in the HMT group, 39 (47.0%) attained any response to HMT including complete response, partial response, marrow complete response, and hematologic improvement. Survival data were the followings: OS, HMT vs. IC vs. SC, median 62.5 vs. 16.7 vs. 21.0 months; PFS, median 37.7 vs. 13.8 vs. 17.8 months. Multivariate analyses by stratified time updated Cox model showed that hazard ratio (HR) of HMT compared to SC was 1.029 (95% CI, 0.670–1.582, P=0.895) for OS and 0.539 (95% CI, 0.362–0.803, P=0.002) for PFS. When we performed subgroup analyses in lower risk disease (IPSS Low/Intermediate-1) and higher risk disease (IPSS Intermediate-2/High), the effects of HMT on survivals were different by the risk stratification of MDS. In lower risk MDS, there were no survival benefits of HMT compared to SC (OS, median 53.9 vs. 39.8 months, HR 1.570, P=0.108; PFS, median 37.7 vs. 52.5 months, HR 0.880, P=0.633), whereas both OS and PFS were significantly longer in HMT compared to SC (OS, median 137.9 vs. 5.9 months, HR 0.289, P=0.043; PFS, median 80.2 vs. 0.9 months, HR 0.154, P<0.001). Conclusion: Our data suggested that hypomethylating therapy could improve the survivals (OS and PFS) of the patients with higher risk MDS. Disclosures: No relevant conflicts of interest to declare.

Investigation of a 22-gene genomic classifier (GC) for risk stratification and molecular subtyping in an Asian prostate cancer (PCa) cohort.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 249-249
Author(s):  
Wei Loong Sherman Yee ◽  
Wai Yee Woo ◽  
Adelene Sim ◽  
Kar Perng Low ◽  
Alice Meng ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Racial Differences ◽  
White Men ◽  
Risk Groups ◽  
Molecular Subtyping ◽  
Basal Subtype ◽  
Grid Database ◽  
Risk Patients ◽  
Very High

249 Background: A 22-gene GC has been proposed to refine risk stratification of localized PCa by conventional NCCN criteria, and this may potentially influence treatment recommendations. Nonetheless, majority of studies looking at the utility of GC were conducted in White and non-White men from Western cohorts. We therefore investigated the association of GC with NCCN risk groups (RG) in an Asian PCa cohort. Additionally, we examined for inter-racial differences in molecular subtyping between Asian and White/non-White PCa. Methods: GC (Decipher Biosciences Inc., CA) was performed on diagnostic biopsies of men who were treated with radiotherapy +/- hormonal therapy at a single institution (N = 75). ISUP Gleason’s grade (GG) and tumor cellularity were reviewed by an expert GU pathologist. RNA was extracted from 2 x 2.0-mm tumor cores using Qiagen AllPrep DNA/RNA FFPE Kit (Qiagen, Germany) and gene expression was performed on Affymetrix Human Exon 1.0 ST Array (ThermoFischer, CA). PAM50 molecular subtyping was derived using the DecipherGRID database. Results: We profiled 80 tumors from 75 patients, comprising of 18 (24.0%), 9 (12.0%), 21 (28.0%), and 19 (25.3%) NCCN low-/favorable intermediate-, unfavorable intermediate-, high- and very high-RG, respectively; of note, 8 (10.7%) patients had regional/metastatic disease at diagnosis. Using the GC, 27 (33.8%), 14 (17.5%) and 39 (48.8%) were classified as low- (<0.45), intermediate- (0.45-0.6) and high-RG, respectively (>0.6). When stratified using a three-tier clinico-genomic (CG) classification system (Spratt et al. 2017), 6 of 21 (28.6%) NCCN-defined high-risk and 4 of 19 (21.1%) very high-risk patients were downgraded to CG-defined intermediate-/low-risk, while 2 of 27 (7.4%) NCCN low-/intermediate-risk patients were in fact upgraded to CG high-risk. Next, we interrogated the PAM50 basal-luminal signature in our cohort. Interestingly, when matched to White (N = 5762) and non-White (N = 155) for NCCN RG, ISUP GG and age, we observed a high proportion of basal subtype (62.7%) in Asians, which contrasted the prevalence observed in White (16.7%) and non-White (15.9%) North American patients (Chi-sq P <0.001). Conclusions: Here, we demonstrated the utility of the 22-gene GC for refining the NCCN risk stratification in a largest Asian PCa dataset to-date. An unexpectedly high proportion of PAM50 basal-subtype was observed, suggesting race-specific differences of the tumor transcriptome.

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.

Abstract P275: Demographic and Clinical Profile of Patients with Risk Factors for Coronary Heart Disease (CHD) Defined by National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III Guidelines

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
David M Kern ◽  
Sanjeev Balu ◽  
Ozgur Tunceli ◽  
Swetha Raparla ◽  
Deborah Anzalone
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Groups ◽  
Lipid Lowering ◽  
High Risk Patients ◽  
Low Hdl ◽  
Risk Patients ◽  
Artery Disease ◽  
Very High ◽  
Statin Use

Introduction: This study aimed to compare the demographic and clinical characteristics of patients with different risk factors for CHD as defined by NCEP ATP III guidelines. Methods: Dyslipidemia patients (≥1 medical claim for dyslipidemia, ≥1 pharmacy claim for a statin, or ≥1 LDL-C value ≥100 mg/dL [index date]) aged ≥18 y were identified from the HealthCore Integrated Research Environment from 1/1/2007-7/31/2012. Patients were classified as low risk (0 or 1 risk factor): hypertension, age ≥45 y [men] or ≥55 y [women], or low HDL-C), moderate/moderately high risk (≥2 risk factors), high risk (having CHD or CHD risk equivalent), or very high risk (having ACS or other established cardiovascular disease plus diabetes or metabolic syndrome). Demographics, comorbidities, medication use and lipid levels during the 12 months prior, and statin use during the 6 months post-index date were compared across risk groups (very high vs each other risk group). Results: There were 1,524,351 low-risk (mean age: 47 y; 45% men), 242,357 moderate-risk (mean age: 58 y; 59% men), 188,222 high-risk (mean age: 57 y; 52% men), and 57,469 very-high-risk (mean age: 63 y; 61% men) patients identified. Mean Deyo-Charlson comorbidity score differed greatly across risk strata: 0.20, 0.33, 1.26, and 2.22 from low to very high risk (p<.0001 for each). Compared with high-risk patients, very-high-risk patients had a higher rate of ischemic stroke: 5.4% vs 4.1%; peripheral artery disease: 17.1% vs 11.6%; coronary artery disease: 8.5% vs 8.2%; and abdominal aortic aneurysm: 2.3% vs 2.0% (p<.05 for each). Less than 1% of the total population had a prior prescription for each non-statin lipid-lowering medication (bile acid sequestrants, fibrates, ezetimibe, niacin, and omega-3). Very-high-risk patients had lower total cholesterol (very-high-risk mean: 194 mg/dL vs 207, 205, and 198 mg/dL for low-, moderate-/moderately-high-, and high-risk patients, respectively) and LDL-C (very-high-risk mean: 110 mg/dL vs 126, 126, and 116 mg/dL for the other risk groups; p<.0001 for each); higher triglycerides (TG) (very-high-risk mean: 206 mg/dL vs 123, 177, and 167 mg/dL for the other groups; p<.0001 for each); and lower HDL-C (very-high-risk mean: 45 mg/dL vs 57 [p<.0001], 45 [p=.006], and 51 mg/dL [p<.0001]). Statin use was low overall (15%), but higher in the very-high-risk group (45%) vs the high- (29%), moderate-/moderately-high- (18%), and low- (12%) risk groups (p<.0001 for each). Conclusions: Despite a large proportion of patients having high lipid levels, statin use after a dyslipidemia diagnosis was low: ≥80% of all patients (and more than half at very high risk) failed to receive a statin, indicating a potentially large population of patients who could benefit from statin treatment. Prior use of non-statin lipid-lowering medications was also low considering the high TG and low HDL-C levels among high-risk patients.

scholarly journals MIPSS70+ v2.0 predicts long-term survival in myelofibrosis after allogeneic HCT with the Flu/Mel conditioning regimen

2019 ◽  
Vol 3 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Haris Ali ◽  
Ibrahim Aldoss ◽  
Dongyun Yang ◽  
Sally Mokhtari ◽  
Samer Khaled ◽  
...  
Keyword(s):  
Molecular Markers ◽  
High Risk ◽  
Scoring System ◽  
Conditioning Regimen ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients ◽  
Transplantation Outcomes ◽  
Very High

Abstract Although allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF), data are limited on how molecular markers predict transplantation outcomes. We retrospectively evaluated transplantation outcomes of 110 consecutive MF patients who underwent allo-HCT with a fludarabine/melphalan (Flu/Mel) conditioning regimen at our center and assessed the impact of molecular markers on outcomes based on a 72-gene next-generation sequencing panel and Mutation-Enhanced International Prognostic Scoring System 70+ v2.0 (MIPSS70+ v2.0). With a median follow-up of 63.7 months, the 5-year overall survival (OS) rate was 65% and the nonrelapse mortality (NRM) rate was 17%. In mutational analysis, JAK2 V617F and ASXL1 mutations were the most common. By univariable analysis, higher Dynamic International Prognostic Scoring System scores, unrelated donor type, and very-high-risk cytogenetics were significantly associated with lower OS. Only CBL mutations were significantly associated with lower OS (hazard ratio [HR], 2.64; P = .032) and increased NRM (HR, 3.68; P = .004) after allo-HCT, but CALR, ASXL1, and IDH mutations did not have an impact on transplantation outcomes. Patient classification per MIPSS70 showed worse OS for high-risk (HR, 0.49; P = .039) compared with intermediate-risk patients. Classification per MIPSS70+ v2.0 demonstrated better OS when intermediate-risk patients were compared with high-risk patients (HR, 0.291) and much lower OS when very-high-risk patients were compared with high-risk patients (HR, 5.05; P ≤ .001). In summary, we present one of the largest single-center experiences of Flu/Mel-based allo-HCT, demonstrating that revised cytogenetic changes and MIPSS70+ v2.0 score predict transplantation outcomes, and thus can better inform physicians and patients in making decisions about allo-HCT.

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