scholarly journals Eritropoietina Sérica como Marcador Prognóstico em Síndrome Mielodisplásica

2015 ◽  
Vol 28 (6) ◽  
pp. 720 ◽  
Author(s):  
Emília Cortesão ◽  
Rita Tenreiro ◽  
Sofia Ramos ◽  
Marta Pereira ◽  
Paula César ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Acute Leukaemia ◽  
Scoring System ◽  
De Novo ◽  
International Prognostic Scoring System ◽  
Lower Survival ◽  
Prognostic Indices ◽  
Serum Erythropoietin

<strong>Introduction:</strong> This myelodysplastic syndromes are a heterogeneous entity characterized by dysplasia, hypercellular bone marrow, cytopenias and risk of transformation to acute leukaemia. Prognostic factors, such as bone marrow fibrosis, lactate dehydrogenase and β2-microglobulin elevation have been described, but treatment is mainly based in the International Prognostic Scoring System.<br /><strong>Material and Methods:</strong> Our aim was to analyze serum´s erythropoietin at diagnosis in de novo myelodysplastic syndromes patients, through its impact in overall survival and possible implementation as prognostic marker. Clinical and laboratorial data from 102 patients with de novo myelodysplastic syndromes diagnosed between October/2009 and March/2014 were collected. Survival analysis was performed according to serum erythropoietin level stratification, using Kaplan-Meier methodology.<br /><strong>Results:</strong> Our 102 patients had a median age of 74 years, with a male:female ratio of 0.8. Mean erythropoietin was significantly lower in refractory cytopenia with unilineage dysplasia patients in contrast with the higher values observed in 5q- syndrome (p &lt; 0.05). Eleven patients progressed to acute leukaemia; these have higher mean erythropoietin values (p &lt; 0.05). In addition, elevated serum erythropoietin was associated with lower survival rates (p = 0.0336). Predictive value of serum erythropoietin was maintained after Cox regression adjustment. In multivariate analysis, serum erythropoietin is an independent survival predictor (p &lt; 0.001).<br /><strong>Discussion:</strong> Serum erythropoietin is a predictive factor for response to therapy with subcutaneous erythropoietin, and patients with myelodysplastic syndromes with higher values of erythropoietin have poorer response to administration of erythropoietin even at higher doses. Our sample shows that serum erythropoietin also has prognostic value, and in all myelodysplastic syndromes subtypes. Moreover, alone or in combination with other factors or prognostic indices, erythropoietin may enhance the prognostic indices such as the International Prognostic Scoring System, since high levels are associated with progression to acute leukemia and hence lower survival.<br /><strong>Conclusion:</strong> This study suggests that increased erythropoietin levels at diagnosis can by itself be a poor prognosis factor in<br />myelodysplastic syndromes patients, with higher values in patients with progression to acute leukaemia and decreased overall survival.

scholarly journals Coalesced Multicentric Analysis of 2,351 Patients With Myelodysplastic Syndromes Indicates an Underestimation of Poor-Risk Cytogenetics of Myelodysplastic Syndromes in the International Prognostic Scoring System

2011 ◽  
Vol 29 (15) ◽  
pp. 1963-1970 ◽  
Author(s):  
Julie Schanz ◽  
Christian Steidl ◽  
Christa Fonatsch ◽  
Michael Pfeilstöcker ◽  
Thomas Nösslinger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
International Prognostic Scoring System ◽  
Prognostic Impact ◽  
Bone Marrow Blast ◽  
Poor Risk ◽  
Blast Count ◽  
The Impact

Purpose The International Prognostic Scoring System (IPSS) remains the most commonly used system for risk classification in myelodysplastic syndromes (MDSs). The IPSS gives more weight to blast count than to cytogenetics. However, previous publications suggested that cytogenetics are underweighted in the IPSS. Here we investigate the prognostic impact of cytogenetic subgroups compared with that of bone marrow blast count in a large, multicentric, international patient cohort. Patients and Methods In total, 2,351 patients with MDS who have records in the German-Austrian and the MD Anderson Cancer Center databases were included and analyzed in univariate and multivariate models regarding overall survival and risk of transformation to acute myeloid leukemia (AML). The data were analyzed separately for patients treated with supportive care without specific therapy, with AML-like chemotherapy, or with other therapy regimens (low-dose chemotherapy, demethylating agents, immune modulating agents, valproic acid, and cyclosporine). Results The prognostic impact of poor-risk cytogenetic findings (as defined by the IPSS classification) on overall survival was as unfavorable as an increased (> 20%) blast count. The hazard ratio (compared with an abnormal karyotype or a bone marrow blast count < 5%) was 3.3 for poor-risk cytogenetics, 4.8 for complex abnormalities harboring chromosomes 5 and/or 7, and 3.1 for a blast count of 21% to 30% (P < .01 for all categories). The predictive power of the IPSS cytogenetic subgroups was unaffected by type of therapy given. Conclusion The independent prognostic impact of poor-risk cytogenetics on overall survival is equivalent to the impact of high blast counts. This finding should be considered in the upcoming revision of the IPSS.

Clinical Relevance of Bone Marrow Fibrosis and CD34-Positive Cell Clusters in Primary Myelodysplastic Syndromes

2009 ◽  
Vol 27 (5) ◽  
pp. 754-762 ◽  
Author(s):  
Matteo Giovanni Della Porta ◽  
Luca Malcovati ◽  
Emanuela Boveri ◽  
Erica Travaglino ◽  
Daniela Pietra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Transfusion Requirement ◽  
Free Survival ◽  
Cell Clusters ◽  
Multilineage Dysplasia ◽  
Poor Risk ◽  
Marrow Fibrosis

Purpose We studied bone marrow (BM) histologic abnormalities in myelodysplastic syndromes (MDS) classified according to WHO criteria to determine their clinical correlates and prognostic value. Patients and Methods Three hundred one consecutive patients were retrospectively evaluated for BM fibrosis and CD34 immunoreactivity. Marrow fibrosis was assessed following the European consensus guidelines. Results Moderate to severe BM fibrosis was detected in 17% of cases and was associated with multilineage dysplasia (P = .001), high transfusion requirement (P < .001), and poor-risk cytogenetics (P = .007). CD34+ cell clusters were found in 23% of patients and were associated with WHO categories with excess of blasts (P < .001) and poor-risk cytogenetics (P = .001). In multivariable analysis, BM fibrosis and presence of CD34+ cell clusters had independent negative impact on overall survival (P < .001 and P = .019, respectively) and leukemia-free survival (P < .001 and P = .004, respectively). A hierarchical clustering analysis identified three subsets of patients with distinct clinical features. One cluster consisted mainly of patients with BM fibrosis, multilineage dysplasia, and high transfusion requirement; these individuals had lower overall survival and leukemia-free survival (P = .001 and P < .001, respectively). Within patients stratified according to International Prognostic Scoring System and WHO classification–based Prognostic Scoring System categories, BM fibrosis involved a shift to a one-step more advanced risk group. Conclusion BM fibrosis identifies a distinct subgroup of MDS with multilineage dysplasia, high transfusion requirement, and poor prognosis and represents an independent prognostic factor that may be useful in clinical decision making. Furthermore, the presence of CD34+ cell clusters is an independent risk factor for progression to acute leukemia.

scholarly journals Marrow Blast Percentage Impact on High-Grade Myelodysplastic Syndrome By the Revised International Prognostic Scoring System

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5510-5510
Author(s):  
Omar Alkharabsheh ◽  
Mrinal M. Patnaik ◽  
Naseema Gangat ◽  
Kebede H. Begna ◽  
Hassan B. Alkhateeb ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myelodysplastic Syndrome ◽  
Scoring System ◽  
International Prognostic Scoring System ◽  
High Grade ◽  
Survival Difference ◽  
Significant Difference ◽  
Risk Of Progression ◽  
Very High

Abstract Introduction: The revised international prognostic scoring system (IPSS-R) for myelodysplastic syndrome (MDS) is widely accepted and has been validated in multiple studies. Patients with adverse cytogenetics do poorly and that is reflected in this scoring system by having the highest score for cytogenetics; 2 for intermediate, 3 for poor and 4 for very poor. Little is known about the effect of marrow blasts in adverse cytogenetic in the high-grade MDS defined by IPSS-R intermediate (>3), high (>4.5) and very high (>5). The goal is to examine the effect of marrow blast percentage on outcome in patients with adverse cytogenetics that is present in the high-grade MDS. Methods: We performed data collection from the Mayo clinic records for patients with confirmed MDS after obtaining appropriate IRB approval. Patients were divided based on their total IPSS-R score and we extracted high-grade MDS cases with intermediate, high and very-high IPSS-R only. Cytogenetics and baseline CBC were available for analysis. We calculated the survival difference in patients with blasts <5% and patient with blasts of 5% to 19% for every group. Survival estimates were calculated by Kaplan-Meier method and compared by log-rank testing using JMP v.13. Results: Our database had 1300 patients with confirmed MDS, 41% (N=536) are high-grade MDS. From those, the median age was 70 and 70% were males. Median bone marrow blast was 6% (0-19). Baseline hemoglobin is 9.2 g/dL, WBC 2.7, ANC 1.05, and platelets 69. Their cytogenetics were 1% very good, 31% good, 23% intermediate, 16% poor and 29% very poor. The total IPSS-R groups were 39%,31%, and 30% for the intermediate, high, and very-high groups respectively. The overall survival (OS) for the high-grade MDS with marrow blast <5% was 12.3 months and for patients with marrow blasts ≥5% 11.4 months (P=.4). At each high-grade MDS; intermediate, high and very high, there were no statistically significant differences for patients with marrow blasts below or above 5%. In term of risk of progression to AML, patients with blasts ≥5% were at higher risk of progression compared with <5% (25% vs 10% , P<.001), with no statistically significant difference in term of time-to-AML progression. Conclusion: The percentages of bone marrow blasts had no impact on overall survival among patients with high grade MDS. However, patients with ≥5% marrow blasts are at a higher risk for progression to AML. Disclosures Al-Kali: Novartis: Research Funding.

scholarly journals Overall Survival in Patients with Myelofibrosis Who Have Discontinued Ruxolitinib: A Literature Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3457-3457
Author(s):  
Derek Tang ◽  
Ankush Taneja ◽  
Preety Rajora ◽  
Indeg Sly ◽  
Niall James Davison
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
Literature Review ◽  
Survival Data ◽  
Scoring System ◽  
Janus Kinase ◽  
Cochrane Library ◽  
International Prognostic Scoring System ◽  
Independent Reviewer

Introduction: Myelofibrosis (MF) is a rare bone marrow cancer characterized by bone marrow fibrosis and abnormal cytokine expression, often leading to splenomegaly, constitutional symptoms, and cytopenia. Prognostic scoring systems (the International Prognostic Scoring System and the Dynamic International Prognostic Scoring System) classify patients into low-, intermediate-1-, intermediate-2-, or high-risk categories. Most patients with MF have either intermediate-2- or high-risk disease, indicating a poor overall prognosis and short survival time (5-year survival rate in Europe: 35%). Ruxolitinib is the first Janus kinase inhibitor (JAKi) treatment for MF approved by the US Food and Drug Administration and the European Medicines Agency. However, the rate of discontinuation of ruxolitinib in the first 2-3 years of treatment is high (&gt; 50%) due to treatment resistance, disease recurrence, and worsening of anemia. This literature review aimed to assess overall survival (OS) in patients with MF who have discontinued ruxolitinib. Methods: A systematic literature review (SLR) was conducted in which Embase®, MEDLINE®, and the Cochrane Library were searched to identify published evidence from database inception until August 2018. Conference proceedings, health technology assessments, and bibliographies were also searched. Additionally, this SLR was updated in a targeted manner using Embase® until February 2019 to identify and update the OS evidence among patients with MF who have discontinued ruxolitinib. Retrieved studies were included if they were published in English and reported OS data in the targeted patient population of interest. Two independent reviewers assessed the studies against pre-defined eligibility criteria (Table 1) to include or exclude the studies, and any uncertainty was resolved by a third independent reviewer, in the case of the SLR, or by mutual agreement, in the case of the update. All extracted data were quality checked by a second independent reviewer. A descriptive, qualitative analysis was conducted to assess OS in patients with MF who have used and discontinued ruxolitinib. Results: Of the 4,011 publications retrieved, 11 studies were included (Table 2). Six were retrospective observational studies, 2 were randomized controlled trials (RCTs), and 3 were non-RCTs. Across all the included studies, 5 reported estimates of median OS. Across the 4 studies reporting median OS for standard of care or approved treatments, median OS ranged from 4.9-30 months (Kuykendall et al. 2017, Mehra et al. 2016, Newberry et al. 2017, Palandri et al. 2018). Patients receiving no treatment after ruxolitinib had a median OS of 4.9 months (Kuykendall et al., 2017). Median OS in patients who received treatment with salvage therapy or conventional agents (e.g. hydroxyurea, danazol, anagrelide) was typically around 14 months (14, 14, and 15 months in Mehra et al. 2016, Newberry et al. 2017, and Kuykendall et al. 2017, respectively). Estimated median OS following ruxolitinib discontinuation for early discontinuers and spleen responders in the COMFORT-II study was approximately 16.5 months (NICE, 2015). One study reported median OS for an investigational agent (Mascarenhas et al. 2018); median OS was 19.9 and 29.9 months for imetelstat 4.7 mg/kg and 9.4 mg/kg, respectively. Conclusions: This literature review revealed that patients with MF generally experience poor OS after discontinuing ruxolitinib, especially in patients who receive no further treatments. Line of therapy definitions were rarely reported across studies, which may contribute to variations across study findings. In addition, survival estimates after prior ruxolitinib therapy varied depending on the treatment received and the reason for discontinuation of ruxolitinib. Limited survival data for investigational therapies were available from early-stage trials and may be subject to substantial variations in large-scale registrational trials. Some of the studies included in this literature review may be ongoing as they are currently available in abstract form only, and new data may become available in the near future. Sustained efforts to develop more effective treatments for patients with MF who have discontinued ruxolitinib are imminently needed. Disclosures Tang: Celgene Corporation: Employment, Equity Ownership. Taneja:BresMed Health Solutions Ltd: Employment. Rajora:BresMed Health Solutions Ltd: Employment. Sly:BresMed Health Solutions Ltd: Employment. Davison:BresMed Health Solutions Ltd: Employment.

Additional Prognostic Value of Bone Marrow Histology in Patients Subclassified According to the International Prognostic Scoring System for Myelodysplastic Syndromes

2003 ◽  
Vol 21 (2) ◽  
pp. 273-282 ◽  
Author(s):  
E. Verburgh ◽  
R. Achten ◽  
B. Maes ◽  
A. Hagemeijer ◽  
M. Boogaerts ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
Prognostic Value ◽  
Predictive Power ◽  
Intensive Therapy ◽  
International Prognostic Scoring System ◽  
Prognostic System ◽  
Bone Marrow Histology

Purpose: The most recent and powerful prognostic instrument established for myelodysplastic syndromes (MDS) is the International Prognostic Scoring System (IPSS), which is primarily based on medullary blast cell count, number of cytopenias, and cytogenetics. Although this prognostic system has substantial predictive power in MDS, further refinement is necessary, especially as far as lower-risk patients are concerned. Histologic parameters, which have long proved to be associated with outcome, are promising candidates to improve the prognostic accuracy of the IPSS. Therefore, we assessed the additional predictive power of the presence of abnormally localized immature precursors (ALIPs) and CD34 immunoreactivity in bone marrow (BM) biopsies of MDS patients. Patients and Methods: Cytogenetic, morphologic, and clinical data of 184 MDS patients, all from a single institution, were collected, with special emphasis on the determinants of the IPSS score. BM biopsies of 173 patients were analyzed for the presence of ALIP, and CD34 immunoreactivity was assessable in 119 patients. Forty-nine patients received intensive therapy. Results: The presence of ALIP and CD34 immunoreactivity significantly improved the prognostic value of the IPSS, with respect to overall as well as leukemia-free survival, in particular within the lower-risk categories. In contrast to the IPSS, both histologic parameters also were predictive of outcome within the group of intensively treated MDS patients. Conclusion: Our data confirm the importance of histopathologic evaluation in MDS and indicate that determining the presence of ALIP and an increase in CD34 immunostaining in addition to the IPSS score could lead to an improved prognostic subcategorization of MDS patients.

scholarly journals Validation of a Prognostic Model and the Impact of Mutations in Patients With Lower-Risk Myelodysplastic Syndromes

2012 ◽  
Vol 30 (27) ◽  
pp. 3376-3382 ◽  
Author(s):  
Rafael Bejar ◽  
Kristen E. Stevenson ◽  
Bennett A. Caughey ◽  
Omar Abdel-Wahab ◽  
David P. Steensma ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
Prognostic Model ◽  
Prognostic Significance ◽  
International Prognostic Scoring System ◽  
Disease Modifying Therapy ◽  
Md Anderson ◽  
The Impact

Purpose A subset of patients with myelodysplastic syndromes (MDS) who are predicted to have lower-risk disease as defined by the International Prognostic Scoring System (IPSS) demonstrate more aggressive disease and shorter overall survival than expected. The identification of patients with greater-than-predicted prognostic risk could influence the selection of therapy and improve the care of patients with lower-risk MDS. Patients and Methods We performed an independent validation of the MD Anderson Lower-Risk Prognostic Scoring System (LR-PSS) in a cohort of 288 patients with low- or intermediate-1 IPSS risk MDS and examined bone marrow samples from these patients for mutations in 22 genes, including SF3B1, SRSF2, U2AF1, and DNMT3A. Results The LR-PSS successfully stratified patients with lower-risk MDS into three risk categories with significant differences in overall survival (20% in category 1 with median of 5.19 years [95% CI, 3.01 to 10.34 years], 56% in category 2 with median of 2.65 years [95% CI, 2.18 to 3.30 years], and 25% in category 3 with median of 1.11 years [95% CI, 0.82 to 1.51 years]), thus validating this prognostic model. Mutations were identified in 71% of all samples, and mutations associated with a poor prognosis were enriched in the highest-risk LR-PSS category. Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS. Only EZH2 mutations retained prognostic significance in a multivariable model that included LR-PSS and other mutations (hazard ratio, 2.90; 95% CI, 1.85 to 4.52). Conclusion Combining the LR-PSS and EZH2 mutation status identifies 29% of patients with lower-risk MDS with a worse-than-expected prognosis. These patients may benefit from earlier initiation of disease-modifying therapy.

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.

Sign in / Sign up

Export Citation Format

Share Document