Prognosis Of Myelodysplastic Syndromes Research Articles

Factors affecting prognosis in myelodysplastic syndrome: an 11 years’ experience from a tertiary care center

Aims: Myelodysplastic syndrome (MDS) is a clonal bone marrow neoplasia characterized by morphological findings of dysplasia in hematopoietic cells, peripheral cytopenia(s), ineffective hematopoiesis, recurrent genetic abnormalities, and an increased risk of conversion to acute myeloid leukemia (AML). The International Prognostic Scoring System (IPSS) is the most commonly used prognostic classification system for MDS. Classification was made by a combination of morphology, cytopenia, and genetic studies. In this study, we aimed to examine the parameters that affect prognosis in MDS patients, show their effects on mortality, and evaluate their positive or negative effects on the course of the disease. Methods: Two hundred twenty-nine patients who applied to Erciyes University Faculty of Medicine, Department of Hematology, and were diagnosed with MDS according to WHO classification between 2010 and 2020 were included in this retrospective study. Age, gender, additional disease status, laboratory parameters, bone marrow biopsy materials, and genetic mutation analysis data were available. The bone marrow aspiration and biopsy examinations of each patient were evaluated and categorized according to the WHO classification. The prognosis was evaluated according to the data of the patients, survival-exitus, and survival after MDS-AML conversion. Risk scoring was analyzed with three different scoring systems (IPSS, WPSS, and R-IPSS). Results: Of the 229 MDS patients included in the study, 57% (131) were male. The mean age of the patients was 67 years. Age, MDS-AML conversion times, disease duration, cellularity, and pathology blast rate were found to be statistically significant between the groups (p<0.05). Leukocyte, neutrophil, platelet, hematocrit, lymphocyte, monocyte, CRP, erythropoietin, ferritin, and LDH data were found to be statistically significant regarding survival (p<0.05). Age, IPSS risk status 3, and W-PSS risk status 3 were found to be independent risk factors affecting survival. Conclusion: Age, IPSS high risk, and WPSS high risk status were found to be independent risk factors affecting survival. Although our study revealed important data in the analysis of MDS patients, single-center analysis of patients and retrospective analysis revealed the need for further studies.

The Correlation of Gene Mutation and Clinical Characteristics in Patients with Myelodysplastic Syndrome and Prognostic Analysis

To explore the correlation between gene mutations and clinical characteristics, prognosis of myelodysplastic syndromes (MDS). Clinical data of 131 patients with MDS were collected from the First Hospital of Lanzhou University from June 2015 to February 2023, which 19 of them developed into secondary acute myeloid leukemia (sAML) during follow-up time. Second generation sequencing technology was used to detect the mutation types of MDS disease-related genes, drawn gene maps, and analyzed their correlation and prognosis based on the clinical data of patients. The median age of 131 MDS patients was 58(17-86) years old. The ratio of male to female was 1.3∶1. A total of 148 gene mutations and 25 types were found in the center. U2AF1 and ASXL1 were often co-mutations with other genes, which were accompanied by 20q- and normal karyotype (NK) respectively. SETBP1 and SRSF2 were more common in patients over 60 years old, while NPM1 and WT1 under 60 years. Older patients had a higher the number of genetic mutations than younger patients. The incidence of SF3B1 and RUNX1 in males was higher than females and DNMT3A in females was higher than males. The number of gene mutations in sAML was higher than MDS (1.8 vs 1.0, P =0.006). The univariate and multivariate analysis showed that IPSS-R prognostic score≥3.5, TP53 were adverse factors for poor prognosis in MDS patients. Patients with monoallelic mutation（ma-TP53）and wild-type（wt-TP53） TP53 had OS better than biallelic mutation（bi-TP53）(P =0.003). The OS of MDS patients was better than sAML(P =0.01) and transplant patients was significantly better than nontransplant patients(P =0.036). Gene mutation is closely related to cytogenetic indexes and clinical features (peripheral blood cell count, sex, age). IPSS-R prognostic score and TP53 were risk factors affecting OS in MDS patients.

Clinical Relevance of Differential RARα and PPARβ/δ Expression in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are clinically heterogeneous hematological malignancies with an increased risk of transformation to acute myeloid leukemia, emphasizing the importance of identifying new diagnostic and prognostic markers. This study sought to investigate the predictive ability of all-trans retinoic acid (ATRA)-dependent nuclear transcription factors RARα and PPARβ/δ gene expression in MDS patients. Peripheral blood specimens were collected from 49 MDS patients and 15 healthy volunteers. The specimens were further separated in Ficoll density gradient to obtain the mononuclear cells fractions. Gene expression analysis was carried out using quantitative real-time polymerase chain reaction (qRT-PCR) technique. In the mononuclear cell fractions of MDS patients, RARα expression was increased (p<0.05) and PPARβ/δ expression was decreased (p<0.01) compared to healthy volunteers. When RARα and PPARβ/δ expression was compared in groups of MDS patients with different risks of disease progression, no statistically significant difference was found for RARα expression, while PPARβ/δ expression was significantly lower in the high-risk group of patients compared to the low-risk group (p<0.05). The expression of RARα was significantly associated with overall survival (p<0.05). ROC analysis showed that the expression of PPARβ/δ, rather than RARα expression, could have potential diagnostic value for MDS patients (AUC=0.75, p=0.003 and AUC=0.65, p=0.081, respectively). RARα and PPARβ/δ genes are putative biomarkers that may be associated with the diagnosis and prognosis of MDS.

ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.

Granulocyte Colony-Stimulating Factor and Decitabine-Containing Conditioning Improves Survival in Myelodysplastic Syndrome Patients with Iron Overload Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Background: Iron overload is considered as an unfavorable prognosis in myelodysplastic syndrome (MDS) even in those undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although iron chelation therapy has improved the prognosis of these patients to some extent, the effect has not yet been satisfactory. This study aimed to investigate whether granulocyte colony-stimulating factor and decitabine (G-DAC)-containing conditioning improve the prognosis of iron-overloaded MDS patients undergoing allo-HSCT. Study Design: One hundred and ninety-seven patients were enrolled in this retrospective study. Based on the level of serum ferritin (SF) and conditioning regimen, all patients enrolled were divided into 4 groups: SF﹤1000µg/L with G-DAC conditioning (cohort 1), SF﹤1000µg/L with non-G-DAC conditioning (cohort 2), SF ≥ 1000µg/L with G-DAC conditioning (cohort 3) and SF ≥ 1000µg/L with non-G-DAC conditioning (cohort 4). The clinical features and prognosis between cohorts were analyzed. Results: The 2-year overall survival (OS) was 77.0%, 72.1%, 73.8% and 38.7% ( P = 0.001), and disease-free survival (DFS) was 75.7%, 62.8%, 71.7% and 35.5% ( P = 0.001), and the cumulative incidence of non-relapse mortality (NRM) was 17.3%, 25.0%, 15.2% and 53.1% ( P = 0.001), and the incidence of relapse was 8%, 13.6%, 13.1% and 12.5% ( P = 0.592), respectively, in the four groups. To be specific, cohort4 had worse OS and DFS and higher NRM than the other three groups (all P﹤0.05). Multivariate analysis revealed that SF ≥ 1000µg/L was a risk factor for OS, DFS and NRM ( P = 0.022, P = 0.025, P = 0.036), while G-DAC-containin g conditioning was a protective factor ( P = 0.009, P = 0.003, P = 0.004). Intriguingly, when cohort 1 to cohort4 were included in the multivariate analysis, only cohort4 was a risk factor for OS, DFS and NRM (all P﹤0.05), but cohort3, namely iron-overloaded patients who received G-DAC-containing conditioning had no difference in prognosis compared with patients with SF﹤1000µg/L. Conclusions: The poor prognosis of patients with iron overload could be overcome by G-DAC-containing conditioning partly.

Molecular Taxonomy of Myelodysplastic Syndromes and Its Clinical Implications

Background Recurrent genetic abnormalities are responsible for the pathogenesis of myelodysplastic syndromes (MDS) and their biologic heterogeneity, however current classifications of MDS are still largely based on morphology.Here, we propose a molecular taxonomy of MDS and describe its clinical relevance. Methods We assembled a cohort of 3,233 diagnostic MDS or related myeloid neoplasm samples from the International Working Group for the Prognosis of MDS. Gene mutations, copy-number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) events were derived from targeted sequencing of a 152-gene panel. Molecular features were used for unsupervised clustering analysis using Bayesian Dirichlet processes, and the results were manually curated into a rule-based hierarchical classification tree. Results We detected oncogenic mutations, CNAs, and cnLOH events in 91, 43, and 11% of patients, respectively. We validated and extended patterns of co-occurrence and mutual exclusivity between gene mutations and CNAs, and further described (i) specific occurrences in cis between gene mutations and cnLOH events, (ii) distinct patterns of co-mutation between the allelic state of a same locus (haploid LOH or cnLOH associated with -7/del(7q)), or of the same mutated gene ( TP53, TET2), and (iii) distinct patterns of co-mutation between hotspots of the same gene ( U2AF1). These patterns informed feature definition for clustering analysis. We characterized 18 distinct MDS molecular subgroups. The first 16 groups encompassed 86% (n=2,769) of patients and were based on the presence or absence of mutations in 21 genes ( ASXL1, BCOR, BCORL1, DDX41, DNMT3A, EZH2, FLT3, IDH1, IDH2, MLL, MYC, NPM1, SETBP1, SF3B1, SRSF2, STAG2, TET2, TP53, U2AF1, WT1, ZRSR2), and 6 cytogenetic events (inv(3), complex karyotype, der(1;7), -7, del(5q), -Y), as well as LOH at the TP53 and TET2 locus. The molecularly not-otherwise specified (mNOS) group(8%, n=254) corresponded to the presence of other cytogenetic abnormalities and/or mutations in 51 other recurrently mutated genes (&amp;gt;0.5%). The No-event category (6%, n=210) was characterized by the absence of any recurrent drivers in our assay. Groups ranged in size from 0.5% to 14% of patients and were associated with distinct clinical phenotypes ( Fig 1A) and outcomes ( Fig 1B). The median bone marrow blast percentage across groups ranged from 1.5 to 10%, the median overall survival (OS) from 0.9 to 8.2 years, and the 2-year rate of leukemic transformation from 0 to 40%. The representation of molecular groups within blast strata (&amp;lt;5%, 5-9%, 10-19% blast percentages) was highly heterogeneous: 7, 8, and 9 different groups accounted for more than 5% of patients within each blast stratum, respectively. The prognostic impact of blast counts on outcomes depended on the molecular subgroups. Among the 12 molecular groups with at least 10 patients with outcome data in all 3 blast strata, blast count was prognostically significant in 8 of those groups ( SF3B1, CCUS-like, del(5q), bi-TET2, mNOS, BCOR/L1, IDH-STAG2, TP53-complex) and was not significant in 4 groups ( EZH2-ASXL1, -7/SETBP1, DDX41, AML-like). The molecular groups validated established ( TP53-complex, del(5q), SF3B1) and well characterized entities ( DDX41, AML-like), added further evidence to support previously reported subsets ( bi-TET2, der(1;7), CCUS-like), and described novel genetic subsets (-7/ SETBP1, EZH2-ASXL1, IDH-STAG2, BCOR/L1, U2AF157, U2AF134, SRSF2, ZRSR2). Finally, the MDS molecular groups were used to investigate the genetic heterogeneity of secondary/therapy-related MDS (s/t-MDS) and of myelodysplastic/myeloproliferative neoplasms (MDS/MPN). There were 7 and 6 distinct groups that accounted for more that 5% of patients with s/t-MDS or MDS/MPN, respectively. Within each genetic subgroup, s/t-MDS and MDS/MPN had similar clinical and outcome profiles to primary MDS. Conclusions The genetic complexity of MDS can be organized into 18 molecular groups that reflect the underlying genetic basis of the disease. The prognostic influence of bone marrow blasts varied in the individual genetic subgroups, suggesting that the clinical impact of increased blasts depends on the genetic context. The molecular taxonomy derived in this study is clinically relevant and will inform future classification schemas.

The Absolute Monocyte Count at Diagnosis Affects Prognosis in Myelodysplastic Syndromes Independently of the IPSS-R Risk Score.

The absolute monocyte count (AMC) is associated with mortality in a variety of medical conditions. Its prognostic impact in myelodysplastic syndromes (MDSs) is less well studied. Therefore, we investigated its potential prognostic value in a cohort from the Düsseldorf MDS registry in relationship to the revised international prognostic scoring system (IPSS-R). An AMC below the population's median (<0.2 × 109/L) was associated with several adverse disease features such as lower haemoglobin levels, lower count of neutrophils and platelets, and a higher percentage of blasts in the bone marrow. MDS patients with an AMC < 0.2 × 109/L had a significantly higher risk of progression into acute myeloid leukemia (AML). In a univariate, proportional hazards model the effect of the AMC as a continuous variable was modelled via p-splines. We found a U-shaped effect with the lowest hazard around 0.3 × 109/L. Accordingly, an AMC within the last quartile of the population (0.4 × 109/L) was associated with a reduced overall survival independently of IPSS-R, but not with the risk of secondary AML. Considering monocytopenia as a risk factor for AML progression in MDS may provide an additional argument for allogeneic transplantation or the use of hypomethylating agents in patients who are not clear candidates for those treatments according to current prognostic scoring systems and/or recommendations. Further studies are needed to assess the prognostic impact of the AMC in the context of prognostic scoring systems, considering the molecular risk profile, and to identify the mechanisms responsible for the higher mortality in MDS patients with a subtle monocytosis.

Arginine metabolism key enzymes affect the prognosis of myelodysplastic syndrome by interfering with macrophage polarization.

Immune factors contribute to the onset of myelodysplastic syndrome (MDS). Arginine metabolism affects tumor-associated macrophage (TAM) polarization. This study investigated the infiltration of TAMs and effect of arginine metabolism key enzymes on MDS prognosis. We used the GEO (Gene Express Omnibus database) dataset "GSE19429" to analyze and compare metabolism-associated pathways between MDS patients with excess blasts and those without. The markers of TAMs and arginine metabolism key enzymes, including CD68, iNOS, ARG1 and ASS1 were included in this study. A cohort of 79 patients with acute myeloid leukemia or MDS extracted from GenomicScape's online data mining platform was used to analyze the prognostic significance of the mRNA levels. Fifty-eight patients with primary MDS admitted to Sichuan University's West China Hospital from 2013 to 2017 were evaluated for protein levels. The coexpression of CD68, iNOS, and ARG1 was investigated using an Opal polychromatic immunofluorescence kit. The "Arginine and proline metabolism" pathways (padjusted = 0.01) were associated with excess blasts in patients with MDS. In the mRNA expression cohort, patients with low NOS2 (or iNOS) and high ARG1, ASS1, and CD68 expression levels had worse prognosis. Patients with high CD68 (p = 0.01), high iNOS (p < 0.01), low ARG1 (p = 0.01), and negative ASS1 (p = 0.02) protein expression levels had better prognoses. iNOS and ARG1 were coexpressed with CD68 in MDS patients with or without excess blasts, respectively. Arginine metabolism may contribute to the prognosis of patients with MDS by affecting TAM polarization.

High BM plasma S100A8/A9 is associated with a perturbed microenvironmentand poor prognosis in myelodysplastic syndromes.

S100A8/A9 is a proinflammatory protein and plays an essential role in the pathogenesis of myelodysplastic syndromes (MDS) via the S100A8/A9-Toll-like receptors axis. While S100A8/A9 levels have been used as biomarkers in many inflammatory diseases, their clinical relevance has not been conclusively resolved in MDS. To address this, we used an enzyme-linked immunosorbent assay to quantify S100A8/A9 heterodimers in bone marrow (BM) plasma from 215 MDS patients and compared S100A8/A9 levels across patients with various disease risks and genotypes. S100A8/A9 levels correlated with ASXL1 variant allele frequencies significantly. Moreover, mutant ASXL1 with concurrent RUNX1, STAG2, ZRSR2, or EZH2 mutations was associated with higher S100A8/A9 levels. We further showed that higher S100A8/A9 independently predicted inferior leukemia-free survival and overall survival in MDS patients, irrespective of age, Revised International Prognostic Scoring System subgroups, and known detrimental mutations. Lastly, through deep-sequenced transcriptomic analysis, we demonstrated that higher S100A8/A9 in the BM intimated a perturbed microenvironment with enhanced myeloid-derived suppressor cell-mediated tumor immune escape signal, altered metabolism, and impairment in the functions and quantities of CD8+ T cells and NK cells. S100A8/A9 in the BM microenvironment may be a potential biomarker in the prognostication of MDS and target for novel therapy.

Research Progress on Gene Mutation and CHIP in Pathogenesis of MDS --Review

With the development of molecular biology techniques, the people's understanding of myelodysplastic syndromes (MDS) has greatly improved, a heterogeneous hematopoietic pre-malignant disorder of the stem cells. Gene mutations include RNA splicing, DNA methylation, chromosome modification, transcription factors, signal transduction kinases, RAS pathways, cohesion complexes, DNA repair, etc. Gene mutation is the determinant of diagnostic typing and therapeutic efficacy of MDS. The new concepts of CHIP and ICUS have aroused people's attention to the elderly patients with clonal hematopoiesis and non-clonal cytopenia but without MDS characteristics, who have the possibility of high-risk transformation to MDS and leukemia. In order to better understand the pathogenesis of MDS, the significance of gene mutations, CHIP and ICUS in the diagnosis and prognosis of MDS were reviewed in this paper.

LEP promoter methylation in the initiation and progression of clonal cytopenia of undetermined significance and myelodysplastic syndrome

BackgroundIdiopathic non-clonal cytopenia (ICUS) and clonal cytopenia (CCUS) are common in the elderly population. While these entities have similar clinical presentations with peripheral blood cytopenia and less than 10% bone marrow dysplasia, their malignant potential is different and the biological relationship between these disorders and myeloid neoplasms such as myelodysplastic syndrome (MDS) is not fully understood. Aberrant DNA methylation has previously been described to play a vital role in MDS and acute myeloid leukemia (AML) pathogenesis. In addition, obesity confers a poorer prognosis in MDS with inferior overall survival and a higher rate of AML transformation. In this study, we measured DNA methylation of the promoter for the obesity-regulated gene LEP, encoding leptin, in hematopoietic cells from ICUS, CCUS and MDS patients and healthy controls. We investigated whether LEP promoter methylation is an early event in the development of myeloid neoplasms and whether it is associated with clinical outcome.ResultsWe found that blood cells of patients with ICUS, CCUS and MDS all have a significantly hypermethylated LEP promoter compared to healthy controls and that LEP hypermethylation is associated with anemia, increased bone marrow blast percentage, and lower plasma leptin levels. MDS patients with a high LEP promoter methylation have a higher risk of progression, shorter progression-free survival, and inferior overall survival. Furthermore, LEP promoter methylation was an independent risk factor for the progression of MDS in a multivariate Cox regression analysis.ConclusionIn conclusion, hypermethylation of the LEP promoter is an early and frequent event in myeloid neoplasms and is associated with a worse prognosis.

P099 - Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment: HIGH BM PLASMA S100A8/A9 IS ASSOCIATED WITH A PERTURBED MICROENVIRONMENT AND POOR PROGNOSIS IN MYELODYSPLASTIC SYNDROMES

P099 - Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment: HIGH BM PLASMA S100A8/A9 IS ASSOCIATED WITH A PERTURBED MICROENVIRONMENT AND POOR PROGNOSIS IN MYELODYSPLASTIC SYNDROMES

High Co-Expression of PDCD1/TIGIT/CD47/KIR3DL2 in Bone Marrow Is Associated with Poor Prognosis for Patients with Myelodysplastic Syndrome.

Cellular immune disorder is a common characteristic of myelodysplastic syndrome (MDS). Abnormal natural killer (NK) cell function has been reported in MDS patients, and this is closely related to disease progression and poor prognosis. However, little is known about the association between the abnormal immune checkpoint (IC) that results in abnormal immune NK cell function and the prognosis of MDS. In this study, RNA-sequencing data from 80 patients in the GSE114922 dataset and bone marrow (BM) samples from 46 patients with MDS in our clinical center were used for overall survival (OS) analysis and validation. We found that the NK cell-related IC genes PDCD1, TIGIT, CD47, and KIR3DL2 had higher expression and correlated with poor OS for MDS patients. High expression of PDCD1 or TIGIT was significantly associated with poor OS for MDS patients younger than 60 years of age. Moreover, co-expression of PDCD1 and TIGIT had the greatest contribution to OS prediction. Interestingly, PDCD1, TIGIT, CD47, and KIR3DL2 and risk stratification based on the Revised International Prognostic Scoring System were used to construct a nomogram model, which could visually predict the 1-, 2-, and 3-year survival rates of MDS patients. In summary, high expression of IC receptors in the BM of MDS patients was associated with poor OS. The co-expression patterns of PDCD1, TIGIT, CD47, and KIR3DL2 might provide novel insights into designing combined targeted therapies for MDS.

Validation of the Molecular International Prognostic Scoring System in patients with myelodysplastic syndromes

Letter to Blood| April 6, 2023 Validation of the Molecular International Prognostic Scoring System in patients with myelodysplastic syndromes Clinical Trials & Observations Tariq Kewan, Tariq Kewan Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OHDepartment of Hematology and Oncology, Yale University, New Haven, CT https://orcid.org/0000-0003-4651-5125 Search for other works by this author on: This Site PubMed Google Scholar Waled Bahaj, Waled Bahaj Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH Search for other works by this author on: This Site PubMed Google Scholar Arda Durmaz, Arda Durmaz Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OHSystems Biology and Bioinformatics Department, School of Medicine, Case Western Reserve University, Cleveland, OH https://orcid.org/0000-0001-8394-600X Search for other works by this author on: This Site PubMed Google Scholar Mai Aly, Mai Aly Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OHFaculty of Medicine, Assiut University, Assiut, Egypt https://orcid.org/0000-0002-3926-6856 Search for other works by this author on: This Site PubMed Google Scholar Olisaemeka D. Ogbue, Olisaemeka D. Ogbue Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH Search for other works by this author on: This Site PubMed Google Scholar Hetty E. Carraway, Hetty E. Carraway Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH https://orcid.org/0000-0001-5241-3614 Search for other works by this author on: This Site PubMed Google Scholar Mikkael A. Sekeres, Mikkael A. Sekeres Department of Hematology and Oncology, University of Miami, Miami, FL Search for other works by this author on: This Site PubMed Google Scholar Valeria Visconte, Valeria Visconte Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH Search for other works by this author on: This Site PubMed Google Scholar Carmelo Gurnari, Carmelo Gurnari Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OHDepartment of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy https://orcid.org/0000-0001-6829-5544 Search for other works by this author on: This Site PubMed Google Scholar Jaroslaw P. Maciejewski Jaroslaw P. Maciejewski Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH Search for other works by this author on: This Site PubMed Google Scholar Blood (2023) 141 (14): 1768–1772. https://doi.org/10.1182/blood.2022018896 Article history Submitted: October 28, 2022 Accepted: January 17, 2023 Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Tariq Kewan, Waled Bahaj, Arda Durmaz, Mai Aly, Olisaemeka D. Ogbue, Hetty E. Carraway, Mikkael A. Sekeres, Valeria Visconte, Carmelo Gurnari, Jaroslaw P. Maciejewski; Validation of the Molecular International Prognostic Scoring System in patients with myelodysplastic syndromes. Blood 2023; 141 (14): 1768–1772. doi: https://doi.org/10.1182/blood.2022018896 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Clinical Trials and Observations, Myeloid Neoplasia TO THE EDITOR: Myelodysplastic syndrome (MDS) represents a heterogeneous group of disorders encompassing a wide range of pathologically distinct subtypes associated with different outcomes. Until recently, clinical and cytogenetic features have dominated the pathological classification and the prognostication of MDS.1-3 The wide use of next-generation sequencing and subsequent molecular studies have examined the impact of different genetic alterations on the pathogenetic derivation, diagnostic assignment, and disease prognosis.4-9 The latest contribution to the task of adopting molecular features into the clinical prognostic scheme is represented by the Molecular International Prognostic Scoring System (IPSS-M), a product of the International Working Group for Prognosis in MDS (IWG-PM).10 Here, we took advantage of a large cohort of patients with MDS (n = 1281, supplemental Methods, available on the Blood website) to validate the novel IPSS-M and to compare the score with the...

Clinical significance of prognostic nutritional index in myelodysplastic syndrome

ABSTRACTBackgroundPrognostic nutritional index has been found to be related to the clinical outcomes of patients with cancer. However, its role in myelodysplastic syndromes (MDS) patients is unclear. We aimed to assess the value of nutritional status in predicting the prognosis of MDS patients.MethodsTotally 121 MDS patients were analyzed retrospectively. The prognostic nutritional index (PNI) was used to assess nutritional status of the patients. The bio-informatics tool X-tile was used to define the threshold, and accordingly patients were divided into PNIlow and PNIhigh groups, the characteristics were compared between two groups.ResultsThe PNIhigh was associated with better OS (Overall Survival) than PNIlow in MDS patients (Median OS, 28.03 months versus 19.63 months, P = 0.0205). But there were no statistical differences in PFS (Progression-Free-Survival) between the two groups (P = 0.9373). The univariable and multivariable COX proportional hazard analysis adjusted for age, gender, platelet count, HB level and IPSS-R scores, and the results showed that PNI is a useful index in the evaluation of the OS of MDS (HR 0.588, 95%CI 0.374–0.926, P = 0.024).ConclusionPNI would be a simple and immediately available tool for predicting the prognosis of MDS.

The value of serum IL-4 to predict the survival of MDS patients

BackgroundImmune indicators are routinely used for the detection of myelodysplastic syndrome (MDS), but these are not utilized as a reference indicator to assess prognosis in MDS-related prognostic evaluation systems, such as the World Health Organizational prognostic scoring system, the international prostate symptom score, and the revised international prostate symptom score.MethodsWe examined immune indicators, including cluster of differentiation (CD)3, CD4, CD8, CD56, CD19, interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-a, and interferon-γ in 155 newly diagnosed MDS patients. We also conducted a correlation analysis with clinical indices.ResultsIL-4 was found to be a predictor of survival in these 155 patients using the receiver operating characteristic curve, with 5.155 as the cut-off point. Patients with serum IL-4 levels ≥ 5.155 had a lower overall survival (OS) than those with IL-45.155 at diagnosis. Furthermore, multivariate analysis revealed that IL-4 levels > 5.155 were an independent predictor of OS (hazard ratio: 0.237; 95% confidence interval, 0.114–0.779; P = 0.013). In addition, serum IL-4 expression in the three different scoring systems showed significant differences in the survival of medium- to high-risk MDS patients (P = 0.014, P < 0.001, P < 0.001).ConclusionsAccording to our study, IL-4 levels at the time of diagnosis can predict MDS prognosis in patients as a simple index reflecting host systemic immunity.

Fetal hemoglobin level predicts lower-risk myelodysplastic syndrome.

The relationship between fetal hemoglobin (HbF) levels and disease prognosis in patients with myelodysplastic syndrome (MDS) is unclear. This study aimed to clarify the relationship between HbF level and the prognosis of MDS. To this end, data from 217 patients diagnosed with MDS between April 2006 and August 2020 at Ebina General Hospital were analyzed retrospectively. The primary endpoint was leukemia-free survival (LFS) for 5years after diagnosis. HbF levels were significantly higher in patients with MDS than in control patients without MDS (n = 155), with a cut-off value of 0.4%. Higher-risk patients had a similar prognosis regardless of HbF level, but lower-risk patients had longer LFS at intermediate HbF levels. Although prognosis based on pre-treatment HbF levels did not differ significantly among azacitidine-treated patients, prognosis tended to be better in lower-risk patients with intermediate HbF levels. Multivariate analysis showed that the intermediate HbF category correlated with LFS, independently of MDS lower-risk prognostic scoring system (LR-PSS)-related factors. This study is the first to assess the association between HbF levels and the new World Health Organization 2016 criteria for MDS, demonstrating the significance of HbF levels in the prognosis of MDS.

Risk stratifying MDS in the time of precision medicine.

Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by morphologic dysplasia, persistent cytopenia, and a variable risk of evolution to acute myeloid leukemia (AML). Risk stratification is crucial in a patient-centered approach to the treatment of MDS. Based on hematologic parameters and cytogenetic abnormalities, the Revised International Prognostic Scoring System is currently used for this purpose. In the past years, the use of massively parallel DNA sequencing has clarified the genetic basis of MDS and has enabled development of novel diagnostic and prognostic approaches. When conventional cytogenetics is combined with gene sequencing, more than 90% of patients are found to carry a somatic genetic lesion. In addition, a portion of patients has germline variants that predispose them to myeloid neoplasms. The recently developed International Consensus Classification of MDS includes new entities that are molecularly defined-namely, SF3B1-mutant and TP53-mutant MDS. The International Working Group for Prognosis in MDS has just developed the International Prognostic Scoring System-Molecular (IPSS-M) for MDS, which considers hematologic parameters, cytogenetic abnormalities, and somatic gene mutations. The IPSS-M score is personalized and can be obtained using a web-based calculator that returns not only the individual score but also the expected leukemia-free survival, overall survival, and risk of AML transformation. Providing an efficient risk stratification of patients with MDS, the IPSS-M represents a valuable tool for individual risk assessment and treatment decisions.

Prognostic value of ASXL1 mutations in patients with myelodysplastic syndromes and acute myeloid leukemia: A meta-analysis.

Additional sex combs-like 1 (ASXL1) mutations, a hotspot in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), have been frequently reported for their potential prognostic value, but the results are controversial. Therefore, a meta-analysis was performed. Databases, including PubMed, Embase, and Cochrane Library, were searched for relevant studies published up to January 13, 2022. STATA v16.0 software was used to calculate the combined hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and AML transformation. Subgroup analysis was used to explore the effects of the grouping factors on heterogeneity.Ten studies on ASXL1 mutations and the prognosis of MDS were selected. Our results indicate that ASXL1 mutations have an adverse prognostic impact on OS (HR = 1.68,95%CI:1.45-1.94, p < .0001) and AML transformation (HR = 2.20,95% CI:1.68-2.87, p < .0001). The results for different age groups were not significantly different (HR = 1.87,95% CI: 1.31-2.67; HR = 1.62,95% CI:1.35-2.07). Ten studies covering 5816 patients with AML were included. The pooled HR for OS was 1.37 (95% CI:1.20-1.56, p < .0001). ASXL1 mutations were especially associated with a poorer OS in the subgroup aged ≥60 years (HR = 2.86, 95% CI:1.34-6.08, p = .006); when considering cytogenetically normal AML (CN-AML), the HR was 1.78(95% CI:1.27-2.49, p = .001). This meta-analysis indicates an independent, adverse prognostic impact of ASXL1 mutations in patients with MDS and AML, which also applies to patients with CN-AML. Age was a risk factor for patients with AML and ASXL1 mutations but not for patients with MDS.

On the basis of sex: outcomes in myelodysplastic syndromes

Sex has long been relevant in patients with myelodysplastic syndromes given there is a higher prevalence1 and poorer prognosis2 among men compared with women. However, this relationship has been traditionally viewed as one that is confounded by disease genetics or caused by differential responses to therapy,3 and not necessarily as an independent prognostic factor. In The Lancet Haematology, the GenoMed4All consortium4 used large European population datasets to challenge this dogma. The authors' data show that male sex is associated with a poorer prognosis in myelodysplastic syndromes than female sex, particularly in patients with low-risk prognostic scores according to the Revised International Prognostic Scoring System (IPSS-R).