scholarly journals Lower risk but high risk

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 428-434
Author(s):  
Amy E. DeZern
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Myelodysplastic Syndromes ◽  
Genetic Information ◽  
Lower Risk ◽  
Molecular Genetic ◽  
Scoring Systems ◽  
International Prognostic Scoring System ◽  
Disease Characteristics ◽  
Prognostic Scoring Systems

Abstract Risk stratification is crucial to the appropriate management of most cancers, but in patients with myelodysplastic syndromes (MDS), for whom expected survival can vary from a few months to more than a decade, accurate disease prognostication is especially important. Currently, patients with MDS are often grouped into higher-risk (HR) vs lower-risk (LR) disease using clinical prognostic scoring systems, but these systems have limitations. Factors such as molecular genetic information or disease characteristics not captured in the International Prognostic Scoring System–Revised (IPSS-R) can alter risk stratification and identify a subset of patients with LR-MDS who actually behave more like those with HR-MDS. This review describes the current identification and management of patients with LR-MDS whose condition is likely to behave in a less favorable manner than predicted by the IPSS-R.

Prognostic models in myelodysplastic syndromes

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 504-510 ◽  
Author(s):  
Rafael Bejar
Keyword(s):  
Risk Stratification ◽  
Myelodysplastic Syndromes ◽  
Somatic Mutations ◽  
Scoring Systems ◽  
Accurate Estimate ◽  
Prognostic Models ◽  
International Prognostic Scoring System ◽  
Clinical Predictors ◽  
Molecular Abnormalities ◽  
Prognostic Scoring Systems

Abstract Establishing the prognosis for patients with myelodysplastic syndromes (MDS) is a key element of their care. It helps patients understand the severity of their disease and set expectations for their future. For physicians, an accurate estimate of prognosis drives decisions about the timing and choice of therapeutic options to consider. The International Prognostic Scoring System (IPSS) has been the standard tool for MDS risk stratification since it was released in 1997. It has been used to describe patients in pivotal clinical trials and is a key element of practice guidelines. Subsequent changes to the classification scheme for MDS and an underestimation of risk in some patients from the low and intermediate-1 categories have led to the development of several newer prognostic models. The most recent is the revised IPSS (IPSS-R), which addresses several of the perceived deficiencies of its predecessor. Despite their utility, none of the available prognostic systems incorporates disease-related molecular abnormalities such as somatic mutations. These lesions are present in the nearly all cases and many have been shown to improve upon existing prognostic models. However, the interpretation of somatic mutations can be challenging and it is not yet clear how best to combine them with clinical predictors of outcome. Here I review several prognostic scoring systems developed after the IPSS and describe the emerging use of molecular markers to refine risk stratification in the MDS patient population.

scholarly journals Serum Vitamin D Levels in Patients with Myelodysplastic Syndromes: A Retrospective Single-Center Analysis

2019 ◽  
Vol 141 (4) ◽  
pp. 225-231
Author(s):  
Catharina Müller-Thomas ◽  
Heinz Tüchler ◽  
Martina Rudelius ◽  
Heike Schneider ◽  
Sabrina Pfefferkorn ◽  
...  
Keyword(s):  
Vitamin D ◽  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Serum Vitamin ◽  
Innate Immune ◽  
International Prognostic Scoring System ◽  
Lower Serum ◽  
Serum Vitamin D ◽  
Disease Characteristics ◽  
Vitamin D Levels

Background/Aims: There is growing evidence supporting the role of innate immune deregulation and inflammation in the pathogenesis of myelodysplastic syndromes (MDS). Vitamin D (VD) is known to be involved in various immune and epigenetic processes. This analysis aimed to evaluate serum VD levels in patients with MDS and to analyze associations between serum VD levels and disease characteristics. Methods: Serum levels of 25-hydroxyvitamin D3 (25(OH)-D3), the major form of VD in human serum, were measured by chemiluminescence immunoassay in 62 unselected patients with MDS. Associations between serum 25(OH)-D3 levels and disease characteristics were analyzed using Kendall’s tau and two-sided p values. Results: The median serum 25(OH)-D3 level was markedly reduced (17.5 ng/mL). Patients with lower-risk disease features had lower serum 25(OH)-D3 levels than patients with higher-risk disease features with regard to medullary blast counts (16 vs. 31 ng/mL, p < 0.001), the revised international prognostic scoring system (13 vs. 30.5 ng/mL, p = 0.001), and blood counts. Conclusions: We show that patients with lower-risk disease characteristics exhibit lower serum VD levels than patients with higher-risk disease characteristics. Whether these findings might reflect innate immune deregulation has to be investigated in further studies.

Comparison of Risk Models for Patients with Lower Risk Myelodysplastic Syndromes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1919-1919
Author(s):  
Hye Ryoun Kim ◽  
Guillermo Garcia-Manero ◽  
Carlos E. Bueso-Ramos ◽  
Hagop M. Kantarjian ◽  
Sourindra Maiti ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Risk Stratification ◽  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Prognostic Significance ◽  
Gene Mutations ◽  
International Prognostic Scoring System ◽  
Cancer Center ◽  
Study Cohort ◽  
University Of Texas

Abstract Accurate prognostication is essential for patients with myelodysplastic syndromes (MDS) to facilitate optimal patient management. Several systems for predicting the outcome of patients with MDS are commonly used in clinics, including the International Prognostic Scoring System (IPSS), revised IPSS, and a low risk MDS model developed by The University of Texas MD Anderson Cancer Center (MDA). We designed this study to evaluate and compare these three models in lower risk MDS patients in order to accurately identify patients with a poor prognosis who may need early therapeutic intervention. A total of 733 adult patients, median age 69 years (range, 24-91), who were diagnosed as lower risk MDS (IPSS low or intermediate-1) with complete cytogenetic evaluations at MDA were included in this study. Both IPSS and revised IPSS systems stratified the study cohort into groups with significantly different overall survival (OS) (P<0.001 in both). The MDA model further stratified patients into significantly different OS groups (P<0.001), and further stratified the revised IPSS low group (N=248, P<0.001) by OS, but not the very low or intermediate (INT) groups. Because both IPSS models are heavily weighted toward cytogenetic features, but over half of MDS patients present with normal (diploid) cytogenetics, we compared the effectiveness of these models in risk stratification among diploid MDS patients. Without the effects of cytogenetics, all 3 models still stratified OS significantly (P<0.001 for all). Revised IPSS further stratified IPSS low (N=171, P<0.001) and INT-1 (N=184, P=0.005) into significant different OS groups. The MDA model further stratified IPSS low (P=0.041) and INT-1 (p<0.001) into significant different OS groups. Multivariate analyses showed that age, bone marrow blast count, and hemoglobin and platelet levels were independent factors for survival in all MDS patients and in diploid MDS patients, whereas absolute neutrophil count was not significant for either group. Molecular markers hold promise for further risk stratification in diploid MDS patients. We assessed the prognostic significance of common gene mutations, such as NPM1, FLT3, DNMT3A, NRAS and KIT. We also identified a signature of plasma microRNAs of which expression levels can predict survival of diploid MDS patients more accurately than all three models. In summary, the revised IPSS system has improved the stratification of patients in the IPSS low and INT-1 categories. The MDA model improves the OS stratification in IPSS low and INT-1 groups, as well as the revised IPSS low group. All three systems effectively predict survivals in diploid MDS patients. Development of novel molecular markers will enable further risk stratification of MDS patients, especially in the diploid MDS group. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Kantarjian: ARIAD, Pfizer, Amgen: Research Funding. Cooper:InCellerate: Equity Ownership; Sangamo: Patents & Royalties; Targazyme: Consultancy; GE Healthcare: Consultancy; Ferring Pharmaceuticals: Consultancy; Fate Therapeutics: Consultancy; Janssen Pharma: Consultancy; BMS: Consultancy; Miltenyi: Honoraria.

Prognosis and Outcomes in MDS-MPN Unclassifiable: Single Institution Experience of a Rare Disorder

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1698-1698 ◽  
Author(s):  
Ateefa Chaudhury ◽  
Rami S. Komrokji ◽  
Najla H. Al Ali ◽  
Ling Zhang ◽  
Pardis Vafaii ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Stratification ◽  
Scoring System ◽  
Lower Risk ◽  
Research Funding ◽  
Median Overall Survival ◽  
Scoring Systems ◽  
Rare Disorder ◽  
International Prognostic Scoring System ◽  
Cancer Center

Abstract Introduction: The 2008 World Health Organization (WHO) classification has recognized a unique overlap category that has features of proliferation found in myeloproliferative neoplasms (MPN) and also dysplasia found in myelodysplastic syndrome (MDS). The least well characterized of the 4 MDS/MPN overlap diseases is a rare entity known as MDS/MPN Unclassifiable (MDS/MPN-U), comprising <5% of myeloid disorders. Furthermore, given the rarity of this disorder, there is no validated risk stratification scoring system, although there are several commonly used prognostic models for MDS, including the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), and the M.D. Anderson Cancer Center model (MDAS). The objectives of this study were to evaluate the natural history of this very uncommon diagnosis and to determine which of the current scoring symptoms used for MDS best discriminates outcomes. Methods: The Moffitt Cancer Center database of over 3000 MDS patients was used to identify patients with MDS/MPN-U and to subsequently perform a comprehensive chart/pathology review. We then applied IPSS, IPSS-R, and the MDAS scores to each patient in order to compare differences in overall survival (OS) amongst different risk groups within each scoring system. Finally, we compared outcomes in the MDS/MPN-U group with a large number of matched MDS cases from within our database, using the MDAS. Descriptive statistical analyses were utilized. Chi square analysis and t- test were performed to compare categorical and continuous variables. Akaike information criteria (AIC) were used to assess the relative goodness of fit of the models. All data was analyzed using SPSS version 21.0 statistical software. Results: Forty three patients were identified with MDS/MPN-U and were pathologically confirmed to meet WHO criteria. Median age was 71 years (range 55 - 91) and the M:F = 26.17. Median baseline laboratory parameters: WBC 11.2 x 103/dL (range 0.9 - 84.8); Hb 9.7 g/dL (range 5.8-14.4); platelets 137 x 103/uL. Table 1 summarizes risk stratification per current validated MDS scoring systems. The majority of patients had lower risk disease by all the models. Forty of 42 (95%) patients evaluable for prognostic scoring were classified as low/Int-1 by IPSS. However, 11 out of the 40 pts (28%) classified as lower risk by IPSS were upgraded to Int-2 or high risk by MDAS. Twenty-two patients received hypomethylating agents (HMA) as first line treatment after supportive care. Per IWG 2006, 8 of 22, (36%) had complete response, partial remission, or hematologic improvement, 7 (32%) had stable disease, and 6 (27%) had progressive disease. The median OS for all MDS/MPN-U patients was 33 months (95% Confidence Interval 22 - 45). Within each MDS scoring system, statistically significant survival differences were detected between risk stages (table 1). The IPSS-R did not improve the IPSS prognostic value. Patients categorized as lower-risk (low/Int-1) by MDAS had superior survival compared to IPSS. Lastly, we compared outcomes between the 43 MDS/MPN-U patients and 1117 IPSS low/Int-1 matched controls within the MDS database. Median overall survival was inferior in MDS/MPN-U vs. MDS (33.4 mo vs. 57 mo, p = 0.005). In addition, using the MDAS, stage-by-stage, survival was significantly worse in the MDS/MPN-U group. Table 1. Risk Stratification Based on MDS Scoring Systems MDS/MPN-Un (%) Median Overall Survival (mo) P-value IPSS Low Int-1 Int-2 High 15 (35.7)25 (59.5)1 (2.4)1 (2.4) 33.433.312.86.0 < 0.001 IPSS-R Very Low Low Intermediate High Very High 6 (14.3)21 (50)10 (23.8)4 (9.5)1 (2.4) 18.2333.425.112.86.0 0.001 MDAS Low Int-1 Int-2 High 6 (14.3)20 (47.6)13 (31.0)3 (7.1) 52.433.425.16.0 < 0.001 Conclusions: MDS/MPN-U appears to have a variable disease course but with generally poor outcomes, even amongst lower-risk patients classified by MDS scoring systems, and despite a moderate rate of response to treatment. Matched comparisons indicate inferior outcomes compared with similarly staged MDS patients. The MDAS may offer increased discriminatory capacity for determining prognosis based on disease stage. Further work with a larger patient population and cross comparisons to other MDS/MPN diseases will assist further understanding of this rare disorder. Integration of somatic mutations data may compliment the clinical models. Disclosures Komrokji: Novartis: Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; Pharmacylics: Speakers Bureau; Incyte: Consultancy. Lancet:Kalo-Bios: Consultancy; Celgene: Consultancy, Research Funding; Pfizer: Research Funding; Amgen: Consultancy; Seattle Genetics: Consultancy; Boehringer-Ingelheim: Consultancy.

scholarly journals Established and novel agents for myelodysplastic syndromes

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 82-89 ◽  
Author(s):  
Mikkael A. Sekeres ◽  
Aaron T. Gerds
Keyword(s):  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Hematopoietic Cell Transplantation ◽  
Scoring Systems ◽  
The United States ◽  
Immunosuppressive Drugs ◽  
Novel Agents ◽  
Hypomethylating Agents ◽  
Risk Patients ◽  
Prognostic Scoring Systems

Abstract The myelodysplastic syndromes (MDS) are the most commonly diagnosed myeloid malignancy, with >15 000 new cases identified in the United States yearly. Prognostic scoring systems supplant a formal staging approach and, in general, divide patients into those with lower-risk and those with higher-risk MDS. Although treatment goals for patients with lower-risk disease focus on minimizing transfusions and optimizing quality of life, in higher-risk MDS, the goal is to delay transformation to acute leukemia and to prolong survival. In lower-risk patients, isolated cytopenias are treated with erythropoiesis-stimulating agents or growth factors such as thrombopoietin mimetics. For patients with the del(5q) cytogenetic abnormality or those who fail these initial approaches, lenalidomide may be tried, as can experimental agents. Lower-risk patients with multiple cytopenias may be treated with immunosuppressive drugs or low-dose hypomethylating agents. For patients with higher-risk disease, hypomethylating agents are the preferred initial treatment approach, with evaluation for hematopoietic cell transplantation at diagnosis. Several novel agents are being developed for MDS patients who have failed hypomethylating drugs.

scholarly journals Lowering the boom on lower-risk myelodysplastic syndromes

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 367-372
Author(s):  
Mikkael A. Sekeres ◽  
Bhumika J. Patel
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Antithymocyte Globulin ◽  
Scoring Systems ◽  
Response Criteria ◽  
Hypomethylating Agents ◽  
Bone Marrow Blast ◽  
Molecular Abnormalities ◽  
Prognostic Scoring Systems

Abstract Lower-risk myelodysplastic syndromes are defined using prognostic scoring systems that incorporate data on bone marrow blast percentage, degree and numbers of cytopenias, and cytogenetic abnormalities. Increasingly, these are incorporating molecular abnormalities to further refine risk. Therapy is geared toward predominating cytopenias, with erythropoiesis-stimulating agents luspatercept and lenalidomide used to ameliorate anemia, romiplostim and eltrombopag tackling thrombocytopenia, and hypomethylating agents and antithymocyte globulin palliating pancytopenia. Newer agents on the horizon are abrogating the downstream sequelae of specific molecular mutations. One challenge for the future is in further modifying response criteria to align with improvements that are clinically meaningful to patients.

Arsenic Trioxide in Patients With Myelodysplastic Syndromes: A Phase II Multicenter Study

2006 ◽  
Vol 24 (16) ◽  
pp. 2465-2471 ◽  
Author(s):  
Norbert Vey ◽  
Andre Bosly ◽  
Agnes Guerci ◽  
Walter Feremans ◽  
Herve Dombret ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
International Prognostic Scoring System ◽  
Risk Category ◽  
Moderate Activity ◽  
Loading Dose ◽  
Median Response ◽  
System Risk

Purpose Evaluation of the safety and efficacy of arsenic trioxide in patients with myelodysplastic syndromes (MDS). Patients and Methods MDS patients diagnosed according to standard French-American-British criteria received a loading dose of 0.3 mg/kg per day of arsenic trioxide for 5 days followed by a maintenance dose of 0.25 mg/kg arsenic trioxide twice weekly for 15 weeks. Patients were divided into two cohorts: lower-risk MDS (International Prognostic Scoring System risk category low or intermediate 1) and higher-risk MDS (International Prognostic Scoring System risk category intermediate 2 or high). Modified International Working Group criteria were used for response evaluation. Results Of 115 patients enrolled and treated in the study, 67% of patients were transfusion dependent at baseline; median age was 68 years. Most treatment-related adverse events were mild to moderate. The overall rate of hematologic improvement (intent-to-treat) was 24 (19%) of 115, including one complete and one partial response in the higher-risk cohort. The hematologic response rates were 13 (26%) of 50 and 11 (17%) of 64 in patients with lower-risk and higher-risk MDS, respectively. Major responses were observed in all three hematologic lineages; 16% of RBC transfusion-dependent patients and 29% of platelet transfusion-dependent patients became transfusion independent. At data cut off, the median response duration was 3.4 months, with responses ongoing in nine patients. Conclusion Arsenic trioxide treatment consisting of an initial loading dose followed by maintenance therapy has moderate activity in MDS, inducing hematologic responses in both lower- and higher-risk patients. This activity combined with a manageable adverse effect profile warrants the additional study of arsenic trioxide, particularly in combination therapy, for the treatment of patients with MDS.

Abstract 1772: Electrocardiographic Unrecognized Myocardial Infarction Risk Stratification: Quantitated SPECT Infarct Size Predicts Mortality Independent of Clinical and Exercise Test Variables

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Khawaja Ammar ◽  
Todd D Miller ◽  
David O Hodge ◽  
Richard J Rodeheffer ◽  
Raymond J Gibbons
Keyword(s):  
Myocardial Infarction ◽  
Risk Stratification ◽  
Infarct Size ◽  
Mortality Risk ◽  
Exercise Test ◽  
Prognostic Score ◽  
Scoring Systems ◽  
Threshold Method ◽  
Duke Treadmill Score ◽  
Prognostic Scoring Systems

Background : Unrecognized myocardial infarction (UMI), as diagnosed by surveillance electrocardiography (ECG), has the same poor prognosis as recognized (RMI), independent of ejection fraction or ischemia. The value of post UMI risk stratification by infarct size is unknown. Methods : The study group consisted of 5430 patients who underwent 2 day stress (exercise n = 191, pharmacologic n = 155) and rest Tc-99m sestamibi SPECT studies. UMI was diagnosed if ECG showed Q wave MI in the absence of history of MI. SPECT infarct size was quantitated based on a 60% of peak counts threshold method and was expressed as a percentage of the left ventricle (% LV). The association between infarct size and mortality was adjusted for clinical and exercise test prognostic scoring systems. Results : The population consisted of 346 UMI, 628 RMI, and 4456 patients without MI (No MI). Compared to No MI, mortality risk was increased in UMI (RR 1.7, 95% CI 1.6–1.9; p < 0.001) and RMI (RR 1.6, 95% CI 1.4–1.9; p < 0.001) patients. In the UMI group, infarct size was significantly associated with mortality ( p < 0.001), which persisted after adjustment for Mayo prognostic score alone (available in all patients) ( p < 0.001) and for Mayo prognostic score, Framingham risk score, and Duke treadmill score (data available in 137 patients) ( p < 0.001). For every 10% LV increase in infarct size, mortality risk increased 30% (RR = 1.3, 95% CI 1.2–1.5) (see figure ). Conclusions: In patients with UMI, larger quantitated SPECT infarct size predicts increased mortality independent of clinical and exercise test prognostic scoring systems. This finding supports the use of infarct size imaging for risk stratification of UMI patients.

scholarly journals DNA methylation identifies genetically and prognostically distinct subtypes of myelodysplastic syndromes

2019 ◽  
Vol 3 (19) ◽  
pp. 2845-2858 ◽  
Author(s):  
Brian Reilly ◽  
Tiffany N. Tanaka ◽  
Dinh Diep ◽  
Huwate Yeerna ◽  
Pablo Tamayo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Mononuclear Cells ◽  
Scoring Systems ◽  
Bone Marrow Mononuclear Cells ◽  
Key Points ◽  
Prognostic Scoring Systems

Key Points Targeted DNAm profiling of MDS patient bone marrow mononuclear cells identifies several distinct DNAm clusters. Clusters enrich for specific genetic lesions and show differences in survival independent of clinical prognostic scoring systems..

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