Improved Prognostic Assessment Of Patients With MDS By IPSS-R and MDS-CI

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5207-5207
Author(s):  
Margot van Spronsen ◽  
Margot van Spronsen ◽  
Arjan van de Loosdrecht ◽  
Martine ED Chamuleau
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
High Risk ◽  
Predictive Value ◽  
Scoring System ◽  
Bone Marrow Failure ◽  
Prognostic Assessment ◽  
Co Morbidity ◽  
The Impact

Abstract Purpose Myelodysplastic syndrome (MDS) is a broad spectrum of bone marrow failure syndromes characterized by diversity concerning clinical behavior, influence on patient’s outcome and risk for leukemic evolution. For more accurate prognostic assessment, the International Prognostic Scoring System (IPSS) has been recently revised. The purpose of this single-center study was to validate the r-IPSS and to compare this model with the MD Anderson Risk Model Score (MDAS), the IPSS and the (revised) WHO classification-based Prognostic Scoring System (WPSS(-R)). Furthermore, the predictive value of the MDS-Specific Co-morbidity Index (MDS-CI) as several other prognostic factors were analyzed. Methods Data were retrospectively collected from 222 MDS patients diagnosed at the VUmc between January 2000 and 2013. Selection was based on informative cytogenetics and the availability of peripheral blood and bone marrow counts. The MDAS, (r-)IPSS, (r-)WPSS and MDS-CI were applied and the impact of individual prognostic factors on patients’ outcome was investigated. Kaplan-Meier method was used for estimating survival and the value of prognostic models was determined by Cox’s multivariate regression method. Results Of our study population, 25 (11%), 83 (38%), 51 (23%), 37 (17%) and 25 (11%) patients were classified according to the IPSS-R as very low, low, intermediate, high and very high risk with, respectively, median overall survival (OS) of 129 (95%CI 96-161), 89 (95%CI 73-105), 43 (95%CI 30-57-61), 31 (95%CI 20-42) and 19 (95%CI 7-31) months (P < 0.000). Compared to the MDAS, IPSS, WPSS(-R) and MDAS, the IPSS-R had a higher predictive power for OS. The MDS-CI was of significant predictive value additional to IPSS-R (P < 0.003). Low risk MDS-CI patients who underwent stem cell transplantation (SCT) had a significantly higher mean overall survival (OS), respectively 104 versus 43 months (P < 0.038). However, mean OS of intermediate and high risk MDS patients who received SCT was not better. Conclusion Our data confirm the predictive value of the IPSS-R and show the additional value of the MDS-CI. Combined application of these models refines the prognostic assessment and identifies co-morbidity among MDS patients, which may assist and influence clinical decision making. Disclosures: No relevant conflicts of interest to declare.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

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.

Prognostic factors among 185 adults with newly diagnosed advanced Hodgkin's disease treated with alternating potentially noncross-resistant chemotherapy and intermediate-dose radiation therapy.

1990 ◽  
Vol 8 (7) ◽  
pp. 1173-1186 ◽  
Author(s):  
D J Straus ◽  
J J Gaynor ◽  
J Myers ◽  
D P Merke ◽  
J Caravelli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Prognostic Factors ◽  
High Risk ◽  
Disease Progression ◽  
Striking Difference ◽  
Dose Radiation ◽  
Intermediate Dose

The initial promising results with alternating chemotherapy regimens (mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine [MOPP/ABVD]; lomustine, melphalan, and vindesine [CAD] plus MOPP plus ABV) combined with intermediate-dose radiation therapy (RT) have been sustained with further follow-up; 82.2% of patients (152 of 185) achieved a complete remission (CR), and overall survival is 71.7% +/- 4.4% at 8 years (median follow-up is 55 months among the survivors). No statistically significant differences were found in CR percentage, CR duration, or survival between stages IIB, IIIB, and IV patients. For that reason, stepwise Cox regression analyses to identify the important prognostic factors were performed on overall survival, tumor mortality, freedom from disease progression, and survival following disease progression. Pretreatment characteristics were also tested for association with the probability of achieving CR, CR duration, and death due to other causes. Characteristics that were consistently associated with an independently unfavorable prognosis were low hematocrit, high serum lactic acid dehydrogenase (LDH), age more than 45 years, inguinal node involvement, mediastinal mass greater than .45 of the thoracic diameter, and bone marrow involvement. Patients with two or more unfavorable characteristics were much more likely to fail treatment (median survival, 62.4 months) than those with none or only one unfavorable factor (greater than 95% survival). This striking difference between the low- and high-risk groups remained even if the comparison was restricted to patients less than or equal to 45 years of age. These results provide a basis for selecting the young patients at high risk of failure for more intensive initial treatment with either autologous bone marrow rescue or hematopoietic growth factors.

scholarly journals The Impact of Identifying the Syndromic and Genetic Diagnoses on Hematopoietic Stem Cell Transplantation Outcome in Patients with Inherited Bone Marrow Failure Syndromes

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5015-5015
Author(s):  
Yeon Jung Lim ◽  
Omri Avraham Arbiv ◽  
Melanie Evelyn Kalbfleisch ◽  
Robert J Klaassen ◽  
Conrad Fernandez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Cord Blood ◽  
Bone Marrow Failure ◽  
Stem Cell Source ◽  
Bone Marrow Failure Syndromes ◽  
Cell Source ◽  
Syndromic Diagnosis ◽  
The Impact

Background: Over the last decade major progress has been made in developing new diagnostic methods and in phenotypic and molecular classification of inherited bone marrow failure syndromes (IBMFSs). Nevertheless, data from the Canadian Inherited Marrow Failure Registry (CIMFR) indicates that 28% of patients with inherited bone marrow failure syndromes (IBMFS) cannot be assigned a specific syndromic diagnosis. These unclassified IBMFS (UIBMFS) cases may represent either novel syndromes or atypical presentations of previously described disorders. Hematopoietic stem cell transplantation (HSCT) is the only curative option for bone marrow failure and malignant myeloid transformation in IBMFSs. However, it is unknown whether the application of this treatment to UIBMFS patients without an ability to modify the procedure according to the underlying genetic and syndromic diagnosis affects outcome. To our knowledge, there are no published transplant data on cohorts of patients with UIBMFSs. The aims of this study were to evaluate the outcome and prognostic factors of HSCT in a cohort of patients with UIBMFSs and to determine whether the knowledge of the syndromic/genetic diagnosis before HSCT has an impact on transplant outcome. Methods: Patients were enrolled on the CIMFR if they were diagnosed with a specific IBMFSs (e.g. Fanconi anemia), and/or they had bone marrow failure and either a family history of bone marrow, or physical malformations or a diagnosis before the age of one year. Patients were considered as having an UIBMFS if they fulfilled the above criteria, but could not be assigned a specific syndromic diagnosis since they did not meet the diagnostic criteria for any known IBMFS. HSCT data were extracted from the CIMFR database and analyzed. Descriptive statistics were used to compare between groups. Cox proportional hazards model was used for univariate analysis to identify risk factors for worse overall survival post HSCT in patients with UIBMFSs. Results: Among the patients enrolled in the CIMFR, 22 with UIBMFSs and 68 with classified IBMFSs (CIBMFSs) underwent HSCT between January 2001 and December 31, 2017. Transplanted patients with UIBMFSs were hematologically characterized by multilineage cytopenia (n=13), single-lineage cytopenia (n=1), myelodysplastic syndrome (MDS) (n=5) or acute myeloid leukemia (AML) (n=3). Patients with CIBMFSs had Fanconi anemia (n=30), dyskeratosis congenita (n=7), Shwachman-Diamond syndrome (n=9), Kostmann syndrome (n=6), Diamond-Blackfan anemia (n=4) or others (n= 11). Median age at diagnosis of patients with UIBMFSs was 4.18 years (range; 0 to 32.0 years) and median age at HSCT for UIBMFSs was 5.74 years (range; 0.17-66.67 years). Median time between diagnosis of UIBMFS and HSCT was 0.48 years (range; 0.12 - 34.67), this was significantly shorter than that of CIBMFS (1.77 years, range; 0.17 - 15 years, P=0.014). Six patients (27.3%) of UIBMFS and 9 patients (19.7%) with CIBMFS underwent HSCT for MDS-RCEB or AML (P=0.15). The overall 5-year survival of UIBMFS patients was significantly inferior to that of CIBMFS patients: 56±11.4% vs. 76±5.5%, respectively (P=0.047). 5-year overall survival of patients with UIBMFSs was significantly worse among those whose stem cell source was cord blood (15±13.3%) vs. those who received other stem cell sources (91±8.7%, P=0.04), while stem cell source did not affect prognosis of patients with CIBMFSs. Engraftment failure among UIBMFS patients who received cord blood was significantly higher than engraftment failure among those who received bone marrow (55.6% vs. 9.1%, P=0.024). No other factors reached statistical significance when the impact of stem cell source on overall survival was analyzed, including transfusion load, transplant indications, intensity of conditioning regimens, related/non-related donor, degree of human leukocyte antigen (HLA) matching or identifying a diagnosis after HSCT. Conclusion: Identifying the syndromic diagnosis of IBMFSs is critically important when considering HSCT. The worse HSCT outcome of UIBMFSs in this study might be related to an inability to tailor the transplant approach to the patient specific phenotype and genotype. Our data suggest that cord blood should be avoided as a stem cell source in patients with UIBMFSs. Disclosures No relevant conflicts of interest to declare.

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.

Impact of Megakaryocyte Morphology on Prognosis of Persons with Myelodysplastic Syndromes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2876-2876
Author(s):  
Gege Feng ◽  
Wen Cui ◽  
Wenyu Cai ◽  
Tiejun Qin ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Scoring System ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Systematic Classification ◽  
Significant Difference ◽  
The Impact

Abstract Purpose: To describe the morphological evolution of megakaryocytic dysplasia by developing a systematic classification and evaluate the impact of our classification of dys-megakaryopoiesis on prognosis of persons with MDS. Patients and methods: 423 consecutive patients who had received no prior therapy with MDS diagnosed from January 2000 to April 2014 were enrolled. Follow-up data were available for 371 subjects (88%). Date of last follow-up was December 15, 2014 or date of last contact. Median follow-up was 22 months (range, 1¨C180 months). Subjects with lower-risk MDS fall into Revised International Prognostic scoring systems (IPSS-R) categories of very low-, low-, and intermediate-risk groups and those with higher-risk category into the high- and very high-risk groups. We performed CD41 immune staining and proposed a systematic classification of dys-megakaryopoiesis on bone marrow films: (1) micro-megakaryocytes (<12 µm); (2) micro-megakaryocytes (12-40 µm) with 1 nucleus; (3) micro-megakaryocytes (12-40 µm) with 2 nuclei; (4) micro-megakaryocytes (12-40 um) with multiple nuclei; (5) dys-morphic megakaryocytes (¡Ý40µm) with 1 nucleus; (6) dys-morphic megakaryocytes (¡Ý40 µm) with 2 nuclei; and (7) dys-morphic megakaryocytes (¡Ý40 µm) with multiple nuclei. To evaluate the prognostic impact of dys-megakaryopoiesis based on cell size we divided the seven subtypes into dys-megakaryopoiesis with and without micro-megakaryocytes. Samples were also divided based on numbers of nuclei: (1) mono-nucleated dys-morphic megakaryocytes; (2) bi-nucleated dys-morphic megakaryocytes; and (3) multinucleated dys-morphic megakaryocytes. The best discriminator cutoff point of each group was determined by the minimal P-value approach. The best discriminators were micro-megakaryocytes ¡Ý25%, dys-megakaryopoiesis except micro-megakaryocytes ¡Ý5%, mono-nucleated dys-megakaryopoiesis ¡Ý30% and bi-nucleated dys-megakaryopoiesis ¡Ý1%. In multi-nucleated megakaryopoiesis category, differences in survival at the optimal discriminator were not statistically significant (P=0.10). Results: Subjects in low- and high-risk cohorts were different with platelets (micro-megakaryocytes; P<0.001; dys-megakaryopoiesis except micro-megakaryocytes; P<0.001; mono-nucleated dys-megakaryopoiesis; P<0.001; bi-nucleated dys-megakaryopoiesis; P=0.028), bone marrow blasts (micro-megakaryocytes; P<0.001; dys-megakaryopoiesis except micro-megakaryocytes; P<0.001; mono-nucleated dys-megakaryopoiesis except micro-megakaryocytes; P<0.001; bi-nucleated dys-megakaryopoiesis; P<0.001), WHO 2008 subtypes (dys-megakaryopoiesis; P=0.001; dys-megakaryopoiesis except micro-megakaryocytes; P<0.001; mono-nucleated dys-megakaryopoiesis P<0.001; bi-nucleated dys-megakaryopoiesis; P=0.014) and IPSS-R risk cohorts (micro-megakaryocytes; P<0.001; dys-megakaryopoiesis except micro-megakaryocytes; P<0.001; mono-nucleated dys-megakaryopoiesis; P<0.001; bi-nucleated dys-megakaryopoiesis; P=0.001). There was no significant difference in age, gender, hemoglobin concentration and blood neutrophils levels at diagnosis between low- and high-risk cohorts. In addition, levels of micro-megakaryocytes and mono-nucleated megakaryocytes were significantly associated with IPSS-R cytogenetic category (P=0.002 and P=0.001). A significant association with IPSS-R cytogenetic category was not found for subjects with dys-megakaryopoiesis except micro-megakaryocytes and bi-nucleated megakaryopoiesis (P=0.187 and P=0.654).In multivariate analyses, micro-megakaryocytes ¡Ý25% and mono-nucleated dys-morphic megakaryocytes ¡Ý30% were independent adverse prognostic factors (hazard ratio [HR]=1.56 [95% confidence interval [CI], 1.10, 2.20]; P=0.012 and 1.49 [1.05, 2.10]; P =0.024). These effects were greater than those for other boundaries except micro-megakaryocytes ¡Ý5% and bi-nucleated dys-morphic megakaryocytes ¡Ý1% (P=0.288 and P =0.133). Conclusion: Our data suggest integration of micro-megakaryocytes and mono-nuclear dysmorphic megakaryocytes improves the predictive accuracy of the International Prognostic Scoring System-Revised (IPSS-R) scoring system. Disclosures No relevant conflicts of interest to declare.

scholarly journals CIRCULATING microRNA EXPRESSION IN MYELODYSPLASTIC SYNDROME

2019 ◽  
Vol 141 (7-8) ◽  
pp. 233-237
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Peripheral Blood ◽  
Scoring System ◽  
Molecular Mechanisms ◽  
International Prognostic Scoring System ◽  
Circulating Microrna ◽  
Hematopoietic Stem ◽  
The Impact

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by ineffective hematopoiesis and cytopenia in peripheral blood, where about a third of patients may develop acute myeloid leukemia (AML). The diagnosis of MDS requires the analysis of peripheral blood and bone marrow. Depending on the percentage of blasts in the bone marrow, the number of cytopenias and cytogenetic abnormalities, determination of the prognostic indices is possible (IPSS – „International Prognostic Scoring System“, R-IPSS-„Revised International Prognostic Scoring System“, WPSS – „WHO Prognostic Scoring System“). Until today, numerous studies have been conducted on the molecular mechanisms and epigenetic pathways in myelodysplastic syndrome, and their prognostic and therapeutic importance, but there are few studies analyzing the importance of microRNAs (miRNAs) in MDS. In the last few years, there have been numerous results on the impact of aberrant miRNA expression in malignant disorders where the miRNA represent tumor suppressor genes or oncogenes. Several miRNAs have been recognized as diagnostic and prognostic parameters and possible therapeutic targets. In this paper, we present the overview of recent results on the role of miRNA in MDS.

The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21587-e21587
Author(s):  
Ting Ye ◽  
Jieying Zhang ◽  
Xinyi Liu ◽  
Mengmei Yang ◽  
Yuhan Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Predictive Value ◽  
Cox Regression ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Cox Regression Analysis ◽  
Melanoma Patients ◽  
The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

Endometrial Cancer Lymphadenectomy Trial (ECLAT) (pelvic and para-aortic lymphadenectomy in patients with stage I or II endometrial cancer with high risk of recurrence; AGO-OP.6)

2021 ◽  
Vol 31 (7) ◽  
pp. 1075-1079
Author(s):  
Günter Emons ◽  
Jae-Weon Kim ◽  
Karin Weide ◽  
Nikolaus de Gregorio ◽  
Pauline Wimberger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
High Risk ◽  
Controlled Trial ◽  
Left Renal Vein ◽  
Stage I ◽  
Open Label ◽  
Risk Of Recurrence ◽  
Gynecology And Obstetrics ◽  
The Impact

BackgroundThe impact of comprehensive pelvic and para-aortic lymphadenectomy on survival in patients with stage I or II endometrial cancer with a high risk of recurrence is not reliably documented. The side effects of this procedure, including lymphedema and lymph cysts, are evident.Primary ObjectiveEvaluation of the effect of comprehensive pelvic and para-aortic lymphadenectomy in the absence of bulky nodes on 5 year overall survival of patients with endometrial cancer (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) and a high risk of recurrence.Study HypothesisComprehensive pelvic and para-aortic lymphadenectomy will increase 5 year overall survival from 75% (no lymphadenectomy) to 83%, corresponding to a hazard ratio of 0.65.Trial DesignOpen label, randomized, controlled trial. In arm A, a total hysterectomy plus bilateral salpingo-oophorectomy is performed. In arm B, in addition, a systematic pelvic and para-aortic lymphadenectomy up to the level of the left renal vein is performed. For all patients, vaginal brachytherapy and adjuvant chemotherapy (carboplatin/paclitaxel) are recommended.Major Inclusion CriteriaPatients with histologically confirmed endometrial cancer stages pT1b–pT2, all histological subtypes, and pT1a endometrioid G3, serous, clear cell, or carcinosarcomas can be included when bulky nodes are absent. When hysterectomy has already been performed (eg, for presumed low risk endometrial cancer), study participation is also possible.Exclusion CriteriaPatients with pT1a, G1 or 2 of type 1 histology or uterine sarcomas (except for carcinosarcomas), endometrial cancers of FIGO stage III or IV (except for microscopic lymph node metastases) or visual extrauterine disease.Primary EndpointOverall survival calculated from the date of randomization until death.Sample Size640 patients will be enrolled in the study.Estimated Dates for Completing Accrual and Presenting ResultsAt present, 252 patients have been recruited. Based on this, accrual should be completed in 2025. Results should be presented in 2031.Trial RegistrationNCT03438474.

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