Molecular markers demonstrate diagnostic and prognostic value in the evaluation of myelodysplastic syndromes in cytopenia patients.
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ABSTRACT:
SUBMITTER: He R
PROVIDER: S-EPMC8789920 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Molecular markers demonstrate diagnostic and prognostic value in the evaluation of myelodysplastic syndromes in cytopenia patients.
He Rong R Chiou Jonathan J Chiou Allison A Chen Dong D Chen Constance P CP Spethman Caroline C Bessonen Kurt R KR Oliveira Jennifer L JL Nguyen Phuong L PL Reichard Kaaren K KK Hoyer James D JD Althoff Simon D SD Roh Dana J DJ Miller Mechelle A MA Yuan Ji J Olteanu Horatiu H Begna Kebede K Tefferi Ayalew A Alkhateeb Hassan H Patnaik Mrinal M MM Litzow Mark R MR Al-Kali Aref A Viswanatha David S DS
Blood cancer journal 20220125 1
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Project description:Complex karyotype (CK) is a poor prognosis factor in hematological malignancies. Studies have shown that the presence of CK in myelodysplastic syndrome (MDS) can be associated with MDS progression to acute myeloid leukemia. The goal of this review was to examine the relationship between different types of CK with MDS, as well as its possible role in the deterioration and progression of MDS to leukemia. The content used in this paper has been obtained by a PubMed and Google Scholar search of English language papers (1975-2018) using the terms complex karyotype and myelodysplastic syndromes. A single independent abnormality can be associated with a good prognosis. However, the coexistence of a series of abnormalities can lead to CK, which is associated with the deterioration of MDS and its progression to leukemia. Therefore, CK may be referred to as a prognostic factor in MDS. The detection of independent cytogenetic disorders that altogether can result in CK could be used as a prognostic model for laboratory and clinical use.
| S-EPMC6379782 | biostudies-literature
Project description:Prognosis of lower-risk (International Prognostic Scoring System [IPSS] low/intermediate-1) myelodysplastic syndrome (MDS) is heterogeneous and relies on steady-state assessment of cytopenias. We analyzed relative drops in neutrophil and platelet counts during the first 6 months of follow-up of lower-risk MDS patients. We performed a landmark analysis of overall survival (OS) of lower-risk MDS patients prospectively included in the European LeukaemiaNet MDS registry having a visit at 6 ± 1 month from inclusion to assess the prognostic relevance of relative drops in neutrophils and platelets, defined as (count at landmark - count at inclusion)/count at inclusion. Of 2102 patients, 807 were eligible for the stringent 6-month landmark analysis. Median age was 73 years. Revised IPSS was very low, low, and intermediate/higher in 26%, 43%, and 31% of patients, respectively. A relative drop in platelets >25% at landmark predicted shorter OS (5-year OS, 21.9% vs 48.6% with platelet drop ≤25%, P < 10-4), regardless of baseline IPSS-revised or absolute platelet counts. Relative neutrophil drop >25% had no significant impact on OS. We built a classifier based on red blood cell transfusion dependence (RBC-TD) and relative platelet drop >25% at landmark. Patients with none (62%), either (27%), or both criteria (11%) had 5-year OS of 53.3%, 32.7%, and 9.0%, respectively (P < 10-4). This classifier was validated in an independent cohort of 335 patients. Combining relative platelet drop >25% and RBC-TD at 6 months from diagnosis provides an inexpensive and noninvasive way to predict outcome in lower-risk MDS. This study was registered at www.clinicaltrials.gov as #NCT00600860.
| S-EPMC6113605 | biostudies-literature
Project description:Prolonged isolated thrombocytopenia (PT) is a common complication affecting the outcome of stem cell transplantation. In this study, we undertook a real-world study of 303 myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT) between December 2007 and June 2018. 28.4% of MDS patients suffered from PT after HSCT. Survival analysis indicated that PT was associated with worse overall survival (OS) in MDS patients. The 2-year and 5-year OS in MDS patients with PT after HSCT were 49% and 47%, significantly worse than that of 68% and 60% in patients without PT (P=0.005). For RFS, patients with PT did not have an increased risk of disease relapse (P=0.964). After multivariate adjustment, PT was proved to be the independent risk factor associated with the worse OS (HR 1.49, 95% CI 1.00-2.21, P =0.048). We further analyzed risk factors associated with the occurrence of PT in MDS patients. Multiple logistic regression identified grade II-IV aGVHD, extensive chronic GVHD, hemorrhagic cystitis, and CMV activation as significant risk factors for developing PT. Among these variables, the Odds Ratio (OR) of grade II-IV aGVHD was the highest (P =0.001, OR: 2.65, 95% CI: 1.51-4.64). These data indicated the prognostic value of PT in MDS after HSCT. The identification of risk factors for PT may help improve patient management and lead to the design of effective treatment strategies.
| S-EPMC9309887 | biostudies-literature
Project description:BackgroundMyelodysplastic syndromes (MDS) are a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The controlling nutritional status (CONUT) score, an easy-to-use tool for assessing the nutritional status, was reported as an independent prognostic factor in cancer patients. However, its role in patients with MDS is unclear.ObjectiveWe aimed to explore the impact of CONUT score on the prognosis of patients with MDS, which is of great significance for clinical treatment.MethodsA total of 121 patients with MDS were analyzed. The CONUT score was calculated prior to therapy. The bio-informatics tool X-tile was used to define the CONUT score and the threshold of 4 points was determined to predict the prognosis. Patients were divided into CONUTlow and CONUThigh groups, and the characteristics were compared between two groups.ResultsResults show that CONUTlow was associated with better overall survival (OS) than CONUThigh patients (Median OS, 30.20 vs. 19.63 months, p = 0.0003). However, there were no statistical differences in progression-free survival (PFS) between the two groups (p = 0.2683). Results of univariate and multivariate COX proportional hazard analysis adjusted for bone marrow blasts level, platelet count, International Prognostic Scoring System (IPSS) scores, gender, and hemoglobin (Hb) level showed that the CONUT score was useful in the evaluation standard of OS of MDS (hazard ratio (HR) 2.297, 95% CI 1.441-3.663, p < 0.001).ConclusionsThe CONUT, as a novel immuno-nutritional biomarker, may be useful in predicting the OS of MDS.
| S-EPMC9363897 | biostudies-literature
Project description:PurposeMyelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M.MethodsA total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed.ResultsIPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score.ConclusionIPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may facilitate the clinical implementation of the score.
| S-EPMC10414702 | biostudies-literature
Project description:The clinicopathologic heterogeneity of myelodysplastic syndromes (MDS) is driven by diverse, somatically acquired genetic abnormalities. Recent technological advances have enabled the identification of many new mutations, which have implicated novel pathways in MDS pathogenesis, including RNA splicing and epigenetic regulation of gene expression. Molecular abnormalities, either somatic point mutations or chromosomal lesions, can be identified in the vast majority of MDS cases and underlie specific disease phenotypes. As the full array of molecular abnormalities is characterized, genetic variables are likely to complement standard morphologic evaluation in future MDS classification schemes and risk models.
| S-EPMC3514602 | biostudies-literature
Project description:BackgroundThe recent application of gene-sequencing technology has identified many new somatic mutations in patients with myelodysplastic syndromes (MDS). Among them, serine and arginine rich splicing factor 2 (SRSF2) mutations belonging to the RNA splicing pathway were of interest. Many studies have already reported the potential prognostic value of SRSF2 mutations in MDS patients, with controversial results. Therefore, a meta-analysis was performed to investigate their prognostic impact on MDS.MethodsDatabases, including PubMed, Embase and the Cochrane Library, were searched for relevant studies published up to 14 October 2016. Overall survival (OS) was selected as the primary endpoint, and acute myeloid leukemia (AML) transformation was the secondary endpoint. We extracted the corresponding hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and AML transformation from multivariate Cox proportional hazards models. The combined HRs with their 95% CIs were calculated using fixed or random effect models.ResultsA total of 10 cohort studies, covering 1864 patients with de novo MDS and 294 patients with SRSF2 mutations, were included in the final meta-analysis. Our results indicated that SRSF2 mutations had an adverse prognostic impact on OS (p<0.0001) and AML transformation (p = 0.0005) in the total population. Among the MDS patients with low or intermediate-1 risk defined according to the International Prognostic Scoring System (IPSS), SRSF2 mutations predicted a shorter OS (p = 0.009) and were more likely to transform to AML (p = 0.007).ConclusionsThis meta-analysis indicates an independent, adverse prognostic impact of SRSF2 mutations on OS and AML transformation in patients with de novo MDS. This also applies to the subgroup of low- or intermediate-1-IPSS risk MDS. The identification of mutations in SRSF2 can improve current risk stratification and help make treatment decisions.
| S-EPMC5617234 | biostudies-literature
Project description: Not available
| S-EPMC10933698 | biostudies-literature
Project description:BackgroundRecent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS) that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2).MethodsPretreatment bone marrow (BM) samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR) and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS) and leukemia-free survival (LFS). We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.ResultsIn our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53%) and were significantly correlated with poorer OS (P = 0.007). IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS) (P = 0.039). In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023). We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs) of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09) and 2.21 (95% CI, 1.48-3.30), respectively.ConclusionThe results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.
| S-EPMC4061070 | biostudies-literature
Project description:The inflammasome plays an essential role in lower risk MDS and immune subversion, with the up-regulation of immune checkpoint molecules in the progression to higher-risk disease. In this study, we explored the utility of immune-related biomarkers for the diagnosis and prognosis of MDS. We performed an exploratory, case-control study with 20 randomly selected MDS patients and nine controls with non-inflammatory (n = 3) and inflammatory conditions (n = 6). Patients were stratified in groups of lower (n = 10) and higher risk (n = 10) using IPSS-R. For the exploration of inflammasome and immune checkpoint activities, the expression of caspase-1 (Casp1), programmed cell death protein 1 (PD-1) and its ligand (PD-L1) were assessed in bone marrow samples using immunohistochemistry. In multivariate analysis, we observed significant differences for Casp1 but not PD1/PD-L1 expression in our four conditions (p = 0.003). We found a discordant co-expression of Casp1/PD-L1 in MDS (rho = -0.41, p = 0.07) compared with a concordant co-expression in controls (rho = 0.64, p = 0.06). Neutrophil counts correlated directly with Casp1 (rho = 0.57, p = 0.009) but inversely with PD-L1 expression (rho = -0.58, p = 0.007). We identified characteristic discordant co-expression patterns in lower- (Casp1high/PD-L1low) and higher-risk MDS (Casp1low/PD-L1high), contrasting with concordant patterns in the non-inflammatory (Casp1low/PD-L1low) and inflammatory conditions (Casp1high/PD-L1high). Further validation is warranted in larger, prospective studies.
| S-EPMC8616142 | biostudies-literature