scholarly journals Elevated mature monocytes in bone marrow accompanied with a higher IPSS-R score predicts a poor prognosis in myelodysplastic syndromes

2020 ◽  
Author(s):  
An Wu ◽  
Panpan Gao ◽  
Ningning Wu ◽  
Cong Shi ◽  
Zhenya Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Multivariate Analyses ◽  
International Prognostic Scoring System ◽  
Bone Marrow Blast ◽  
Clinical Value ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Karyotype Analyses ◽  
Independent Adverse Prognostic Factor

Abstract Background: Myelodysplastic syndromes (MDS) is a group of heterogeneousmyeloid clonal diseases originating from hematopoietic stem cells. Clinically, elevated mature monocyte is often observed, but its clinical value still remains unclear.Methods: We retrospectively analyzed a cohort of 235 MDS patients to explore the prognostic value of the percentage of mature monocyte in bone marrow (PMMBM). All patients were divided into elevated PMMBM group and the normal group by 6% PMMBM as the cut-off value. Results: Our results showed that PMMBM>6% was associated with inferior overall survival (OS) (P=0.007) and leukemia-free survival (LFS) (P=0.016) along with higher Revised International Prognostic Scoring System (IPSS-R) score (P<0.0001) and higher frequency of IDH2 mutation (P=0.001). Multivariate analyses showed that besides older age (>60 years), lower hemoglobin level (<10 g/dl), higher bone marrow blast percentage (>5%), poorer karyotype, elevated PMMBM was also an independent adverse prognostic factor for OS in MDS (P=0.049). Conclusions: These findings indicate that increased PMMBM accompanied with a higher IPSS-R score may predict a poor outcome and provide a novel evaluation factor for MDS patients especially when their karyotype analyses fail.

scholarly journals Elevated mature monocytes in bone marrow accompanied with a higher IPSS-R score predicts a poor prognosis in myelodysplastic syndromes

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
An Wu ◽  
Panpan Gao ◽  
Ningning Wu ◽  
Cong Shi ◽  
Zhenya Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Multivariate Analyses ◽  
International Prognostic Scoring System ◽  
Bone Marrow Blast ◽  
Clinical Value ◽  
Hematopoietic Stem ◽  
Adverse Prognostic Factor ◽  
Karyotype Analyses ◽  
Independent Adverse Prognostic Factor

Abstract Background Myelodysplastic syndromes (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. Clinically, elevated mature monocyte in bone marrow is often observed, but its clinical value still remains unclear. Methods We retrospectively analyzed a cohort of 216 MDS patients to explore the prognostic value of the percentage of mature monocyte in bone marrow (PMMBM). All patients were divided into elevated PMMBM group and the normal group by 6% PMMBM as the cut-off value. Results Our results showed that PMMBM> 6% was associated with inferior overall survival (OS) (P = 0.026) along with higher-risk IPSS-R (P = 0.025) and higher frequency of IDH2 mutation (P = 0.007). Multivariate analyses showed that besides older age (> 60 years) for OS, gender (male) for OS, lower neutrophil count (< 0.8 ×  109/L) for OS, higher bone marrow blast percentage (> 5%) for OS and LFS, poorer karyotype for OS, elevated PMMBM was also an independent adverse prognostic factor for OS in MDS (P < 0.0001) but not for LFS (P = 0.736). Conclusions These findings indicate that increased PMMBM may assists Revised International Prognostic Scoring System (IPSS-R) to predict a poor outcome and provide a novel evaluation factor for MDS patients especially when their karyotype analyses fail.

scholarly journals Identification of miR-320 family members as potential diagnostic and prognostic biomarkers in myelodysplastic syndromes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chengyao Wan ◽  
Jing Wen ◽  
Xiaolin Liang ◽  
Qiongni Xie ◽  
Wenqi Wu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Prognostic Score ◽  
Family Members ◽  
Roc Curves ◽  
High Expression ◽  
International Prognostic Scoring System ◽  
Hematopoietic Stem ◽  
Diagnosis And Prognosis ◽  
Kaplan Meier

AbstractMyelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and the abnormal differentiation of hematopoietic stem cells. An increasing number of researches have demonstrated that microRNAs play crucial roles in the pathogenesis of myelodysplastic syndromes. Herein, we aimed to identify novel potential microRNAs bound up with the diagnosis and prognosis of MDS. MiRNA microarray analysis was used to screen deregulated microRNAs in the bone marrow of MDS patients. qRT-PCR was employed to confirm the microarray results. All members of miR-320 family (miR-320a, miR-320b, miR-320c, miR-320d, and miR-320e) were significantly increased in MDS patients compared to normal control. Although we found no correlation between miR-320 family and most clinical characteristics, high miR-320c and miR-320d expression seemed to be associated with high numbers of bone marrow (BM) blasts and worse karyotype. High expression of all the members of the miR-320 family seemed to be associated with a high prognostic score based on International Prognostic Scoring System (IPSS). The areas under the miR-320 family member ROC curves were 0.9037 (P < 0.0001), 0.7515 (P = 0.0002), 0.9647 (P < 0.0001), 0.8064 (P < 0.0001) and 0.9019 (P < 0.0001). Regarding Kaplan–Meier analysis, high miR-320c and miR-320d expression were related to shorter overall survival (OS). Moreover, multivariate analysis revealed the independent prognostic value of miR-320d for OS in MDS. The expression of miR-320 family members was up-regulated in MDS, and miR-320 family members could serve as candidate diagnostic biomarkers for MDS. High expression of miR-320d was an independent prognostic factor for OS in MDS.

scholarly journals The myelodysplastic syndromes: diagnosis, prognosis and therapy

2013 ◽  
pp. 90-97
Author(s):  
Cristina Clissa ◽  
Carlo Finelli ◽  
Antonio De Vivo
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Allogeneic Bone Marrow Transplantation ◽  
Clinical Signs ◽  
The Elderly ◽  
International Prognostic Scoring System ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Risk Class

The authors conducted a systematic review of the medical literature published in the past 15 years on the myelodysplastic syndromes (MDSs). The MDSs are typically seen in the elderly, and primary and secondary forms can be distinguished. This heterogeneous group of hematologic diseases is caused by clonal disorders of pluripotent hematopoietic stem cells. The pathogenesis of the syndromes appears to be multifactorial. Genetic damage, spontaneous or induced by environmental or iatrogenic factors, leads to abnormal proliferation and apoptosis of bone marrow stem cells. The most common presentation is anemia, alone or associated with thrombocytopenia and / or neutropenia, accompanied by the related symptoms and clinical signs (asthenia, fatigue, bleeding, recurrent infections). The diagnosis involves the exclusion of other causes of cytopenia and is based on well-defined, internationally recognized criteria, which are mainly morphologic and cytogenetic. Accurate diagnosis of MDS is essential for prognostic evaluation and for estimating the risk of progression to acute myeloid leukemia (AML). The risk is rated according to the International Prognostic Scoring System (IPSS), which includes 4 levels (low, intermediate-1, intermediate-2, and high). The risk class is a major determinant of the therapeutic approach. Apart from supportive care (transfusions), the main therapeutic tools are erythropoiesis-stimulating agents (ESAs), iron-chelating agents, immunomodulatory drugs, demethylating agents and, in selected cases, allogeneic bone marrow transplantation.

scholarly journals Safety and efficacy of azacitidine in elderly patients with intermediate to high-risk myelodysplastic syndromes

2016 ◽  
Vol 8 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Shyamala C. Navada ◽  
Lewis R. Silverman
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Older Patients ◽  
Bone Marrow Failure ◽  
Common Adverse Effect ◽  
The United States ◽  
International Prognostic Scoring System ◽  
Hematopoietic Stem ◽  
Risk Of Death ◽  
Increased Risk

Myelodysplastic syndromes (MDS) represent a clonal hematopoietic stem cell disorder characterized by morphologic features of dyspoiesis, a hyperproliferative bone marrow, and one or more peripheral blood cytopenias. In patients classified according to the Revised International Prognostic Scoring System (R-IPSS) with intermediate or higher-risk disease, there is an increased risk of death due to progressive bone marrow failure or transformation to acute myeloid leukemia (AML). Azacitidine was the first DNA hypomethylating agent approved by the United States (US) Food and Drug Administration (FDA) for the treatment of MDS and the only therapy that has demonstrated a significant survival benefit over conventional care regimens (CCRs) in patients with intermediate or higher-risk disease. Prolonged survival is independent of achieving a complete remission. Azacitidine has been used in older patients with both clinical and hematological improvement as well as an acceptable side effect profile. The most common adverse effect is myelosuppression. These findings support the use of azacitidine as an effective treatment in older patients with higher-risk MDS.

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.

Monosomal Karyotype In Myelodysplastic Syndromes, with or without Monosomy 7 or 5, Is Prognostically Worse Than An Otherwise Complex Karyotype

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2918-2918
Author(s):  
Mrinal M. Patnaik ◽  
Curtis A. Hanson ◽  
Janice Hodnefield ◽  
Ryan Knudson ◽  
Van Dyke L Daniel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clin Oncol ◽  
Myelodysplastic Syndromes ◽  
World Health ◽  
Complex Karyotype ◽  
Bone Marrow Blast ◽  
Monosomy 7 ◽  
Free Survival ◽  
Autosomal Chromosome ◽  
Monosomal Karyotype

Abstract Abstract 2918 Background: Monosomal karyotype (MK) is defined as the presence of two or more distinct autosomal chromosome monosomies or a single autosomal monosomy associated with at least one structural abnormality (Breems DA et al. J Clin Oncol 2008; 26: 4791). In acute myeloid leukemia (AML), MK has been associated with a worse prognosis than otherwise complex karyotype, regardless of the specific type of autosomal chromosome involved (Breems DA et al. J Clin Oncol 2008; 26: 4791). Whether or not these observations also hold true for myelodysplastic syndromes (MDS) is currently unknown. Objective: To determine if MDS with complex karyotype can be prognostically sub-stratified further based on the presence or absence of MK and if prognosis in MDS with MK is in addition affected by the presence or absence of monosomy 7 or monosomy 5. Methods: The Mayo Clinic database for MDS was used to identify consecutive patients with complex karyotype, defined as the presence of three or more numerical or structural cytogenetic abnormalities. World Health Organization (WHO) criteria were used for MDS diagnosis and leukemic transformation (Vardiman JW et al. Blood 2009; 114: 937). Overall and leukemia-free survivals were calculated from the time of initial cytogenetic studies documenting complex karyotype. Results: A total of 127 MDS patients (median age 70 years; 79 males) with complex karyotype were identified. Amongst them, 106 (83%) met the above-stipulated criteria for MK and 21 (17%) had complex karyotype without monosomies. The MK in the 106 patients included monosomy 7 and/or monosomy 5 in 73 cases. The three complex karyotype subsets (i.e. complex without monosomies vs. MK that included monosomy 7 and/or 5 vs. MK excluding monosomy 7 or 5) were not significantly different in terms of age and sex distribution, hemoglobin level, leukocyte or platelet count, bone marrow blast percentage or International Prognostic Scoring System (IPSS) risk score. However, survival was significantly inferior in patients with MK compared to those with complex karyotype without monosomies (p=0.01; HR 1.9, 95% CI 1.1–3.3). Multivariable analysis identified MK (p=0.002), advanced age (p=0.0004), increased bone marrow blast percentage (0.04), but not IPSS risk category (p=0.34), as independent risk factors for survival. Interestingly, there was no difference in survival among MK patients further sub-stratified by the presence or absence of monosomy 7 and/or monosomy 5 (Figure 1). Although not statistically significant, leukemia-free survival was also worse in patients with MK compared to those with complex karyotype (p=0.11; HR 2.7, 95% CI 0.8–9.0); none of the aforementioned variables significantly affected leukemia-free survival. Conclusions: Monosomal karyotype in MDS identifies a prognostically worse subgroup of patients with complex karyotype. Furthermore, in the context of MK, autosomal monosomies other than monosomy 7 or monosomy 5 are prognostically as detrimental. 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.

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.

Sign in / Sign up

Export Citation Format

Share Document