Diagnosis Of Myelodysplastic Syndrome Research Articles

The Danish Myelodysplastic Syndromes Database: Patient Characteristics and Validity of Data Records.

BackgroundThe Danish Myelodysplastic Syndromes Database (DMDSD) comprises nearly all patients diagnosed with myelodysplastic syndromes (MDS) in Denmark since 2010. The DMDSD has not yet been used for epidemiological research and the quality of registered variables remains to be investigated.ObjectiveTo describe characteristics of the patients registered in the DMDSD and to calculate predictive values and the proportion of missing values of registered data records.MethodsWe performed a nationwide cross-sectional validation study of recorded disease and treatment data on MDS patients during 2010–2019. Patient characteristics and the proportion of missing values were tabulated. A random sample of 12% was drawn to calculate predictive values with 95% confidence intervals (CIs) of 48 variables using information from medical records as a reference standard.ResultsOverall, 2284 patients were identified (median age: 76 years, men 62%). Of these, 10% had therapy-related MDS, and 6% had an antecedent hematological disease. Hemoglobin level was less than 6.2 mmol/L for 59% of patients. Within the first two years of treatment, 59% received transfusions, 35% received erythropoiesis-stimulating agents, and 15% were treated with a hypomethylating agent. For the majority of variables (around 80%), there were no missing data. A total of 260 medical records were available for validation. The positive predictive value of the MDS diagnosis was 92% (95% CI: 88–95). Predictive values ranged from 64% to 100% and exceeded 90% for 36 out of 48 variables. Stratification by year of diagnosis suggested that the positive predictive value of the MDS diagnosis improved from 88% before 2015 to 95% after.ConclusionIn this study, there was a high accuracy of recorded data and a low proportion of missing data. Thus, the DMDSD serves as a valuable data source for future epidemiological studies on MDS.

The clinical and functional effects of TERT variants in myelodysplastic syndrome

AbstractGermline pathogenic TERT variants are associated with short telomeres and an increased risk of developing myelodysplastic syndrome (MDS) among patients with a telomere biology disorder. We identified TERT rare variants in 41 of 1514 MDS patients (2.7%) without a clinical diagnosis of a telomere biology disorder who underwent allogeneic transplantation. Patients with a TERT rare variant had shorter telomere length (P < .001) and younger age at MDS diagnosis (52 vs 59 years, P = .03) than patients without a TERT rare variant. In multivariable models, TERT rare variants were associated with inferior overall survival (P = .034) driven by an increased incidence of nonrelapse mortality (NRM; P = .015). Death from a noninfectious pulmonary cause was more frequent among patients with a TERT rare variant. Most variants were missense substitutions and classified as variants of unknown significance. Therefore, we cloned all rare missense variants and quantified their impact on telomere elongation in a cell-based assay. We found that 90% of TERT rare variants had severe or intermediate impairment in their capacity to elongate telomeres. Using a homology model of human TERT bound to the shelterin protein TPP1, we inferred that TERT rare variants disrupt domain-specific functions, including catalysis, protein–RNA interactions, and recruitment to telomeres. Our results indicate that the contribution of TERT rare variants to MDS pathogenesis and NRM risk is underrecognized. Routine screening for TERT rare variants in MDS patients regardless of age or clinical suspicion may identify clinically inapparent telomere biology disorders and improve transplant outcomes through risk-adapted approaches.

Choosing unwisely: Low-value care in older adults with a diagnosis of myelodysplastic syndrome.

1532 Background: In tandem with the Choosing Wisely initiative, ASCO’s Cost of Care Task Force has proposed a list of low-value (LV) procedures and therapies that may be of limited benefit to patients. Myelodysplastic syndrome (MDS) is the most common myeloid malignancy in the US. A complete diagnostic evaluation (CDE) of MDS requires a bone marrow biopsy, fluorescence in situ hybridization and chromosomal analysis. As a potential LV procedure, we evaluated receipt of CDE in MDS patients with isolated or no cytopenias and no transfusion dependence. Methods: Using national 2011-2014 Medicare data, we identified fee-for-service Medicare patients 66 years of age or older with an MDS diagnosis, one or no cytopenias, and no blood transfusions in the 16 weeks before or after an MDS diagnosis (n = 16,779). We examined the following variables that may have provided a clinical context to (or not to) pursue CDE – demographics (age, race, sex); number of Elixhauser comorbid conditions ( &lt; 5 vs &gt;5); nursing home status, prior history of lymphoma, myeloma, MGUS and other cancers; chronic kidney disease (CKD); colonoscopy; and therapies received including erythropoiesis stimulating agents (ESAs), hypomethylating agents (HMAs) or lenalidomide. We conducted Classification and Regression Tree (CART) analysis, a machine learning approach to identify combinations of factors in patients with little clinical justification for CDE, and Cox proportional hazards regression analysis to compare survival outcomes between those with or without CDE. Results: Over half of our study population (51%) received CDE. Of those, 46.6% were 80 years of age or older, 4.8% were nursing home residents; and 33.6% had 5 or more chronic conditions. Results from CART analysis showed that among patients with an isolated cytopenia (e.g., isolated anemia), 46.0% of patients &gt;80 years (n = 860), and 57.7% (n = 1,156) of those in the 66-79 age group underwent CDE in the absence of CKD, colonoscopy, HMA, or ESA. Among those with no cytopenia (n = 3890), 866 patients received CDE in the absence of HMA, ESA, or history of lymphoma or progression to leukemia. In adjusted analyses, no survival benefit was associated with receipt of CDE (p = 0.24). Conclusions: A substantial number of patients with an MDS diagnosis, isolated or no cytopenias, and no transfusion dependence received a CDE in the absence of other diagnoses, procedures, or therapies that may have explained the clinical decision to perform CDE. These procedures entail costs, pain and anxiety, but do not appear to yield useful information to guide clinical management, as evidenced by the comparable survival outcomes between patients who did and did not undergo CDE. To promote patient-centered care, careful patient selection that reduces unnecessary CDE in MDS patients should be a priority in clinical decision-making.

The association between myelodysplastic syndromes (MDS) and inflammatory bowel diseases (IBD): Analysis of Nationwide Inpatient Sample (NIS) database.

e19033 Background: The co-occurrence of MDS and IBD has been gradually recognized in the literature. Yet, large-scale national studies are required to investigate this observed association further. We aimed to delineate the clinical features, outcomes between the concurrent of MDS with IBD and MDS or IBD alone in a nationally representative database. Methods: Data were obtained from the NIS 2010-2014, using appropriate ICD-9 codes to identify patients who were admitted with a principal diagnosis of MDS with IBD as secondary (MDS-1/IBD) and MDS without IBD and patients who were admitted with a principal diagnosis of IBD with MDS (IBD-1/MDS) and without MDS. We assessed the mortality rate as the primary outcome, mean length of stay (LOS), and rate of blood transfusion as secondary outcomes by Pearson χ2 -test and univariate regression (logistic regression). Results: We identified 190 hospitalizations for MDS-1/IBD and 4895 hospitalizations for IBD-1/MDS. The mean LOS was higher for MDS-1/IBD group than for IBD or MDS only (11.7 vs. 6.1 and 7 days). However, the mortality rate in the MDS-1/IBD group was lower than in patients with IBD or MDS only (2.6% vs. 3.8% and 4.4%). While the rate of blood transfusion was higher among males in the MDS group, it was significantly higher among females when there is a concurrent MDS-1/IBD. However, the differences were not significant when MDS is not the primary diagnosis i.e IBD-1/MDS. In univariate analysis, age and Charlson comorbidity index were significantly associated with an increased mortality rate when there are IBD and MDS than MDS or IBD alone. Conclusions: While unable to assess appropriateness, NIS data indicate that there are significant differences in outcomes such as mean LOS, rate of blood transfusion and mortality rate when there is a concurrence of MDS and IBD than MDS or IBD alone. The underlying pathogenicity remains unclear and warrants additional study.[Table: see text]

A new convolutional neural network predictive model for the automatic recognition of hypogranulated neutrophils in myelodysplastic syndromes

BackgroundDysplastic neutrophils commonly show at least 2/3 reduction of the content of cytoplasmic granules by morphologic examination. Recognition of less granulated dysplastic neutrophils by human eyes is difficult and prone to inter-observer variability. To tackle this problem, we proposed a new deep learning model (DysplasiaNet) able to automatically recognize the presence of hypogranulated dysplastic neutrophils in peripheral blood. MethodsEight models were generated by varying convolutional blocks, number of layer nodes and fully connected layers. Each model was trained for 20 epochs. The five most accurate models were selected for a second stage, being trained again from scratch for 100 epochs. After training, cut-off values were calculated for a granularity score that discerns between normal and dysplastic neutrophils. Furthermore, a threshold value was obtained to quantify the minimum proportion of dysplastic neutrophils in the smear to consider that the patient might have a myelodysplastic syndrome (MDS). The final selected model was the one with the highest accuracy (95.5%). ResultsWe performed a final proof of concept with new patients not involved in previous steps. We reported 95.5% sensitivity, 94.3% specificity, 94% precision, and a global accuracy of 94.85%. ConclusionsThe primary contribution of this work is a predictive model for the automatic recognition in an objective way of hypogranulated neutrophils in peripheral blood smears. We envision the utility of the model implemented as an evaluation tool for MDS diagnosis integrated in the clinical laboratory workflow.

Issue Highlights — May 2021

Issue Highlights — May 2021

A Multifaceted Disease of Problematic Diagnosis in Childhood; Hereditary Hemorrhagic Telangiectasia: A Case Report

Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited in an autosomal dominant manner and may involve skin, mucosa, and internal organs. HHT may cause arteriovenous, arterioportal, and portovenous shunts in the liver, resulting in cirrhosis and portal hypertension. An eight-year-old male patient with a diagnosis of myelodysplastic syndrome for two years was admitted with melena. Portal doppler ultrasonography showed a heterogeneous appearance of the liver parenchyma and splenomegaly (spleen size of 14 cm) with no portal hypertension. An extended etiological investigation for chronic liver disease was conducted. Afterliver biopsy, the patient’s general condition deteriorated, with abdominal distension and reduced hematocrit. The Doppler and hepatic angiography results together with a history of recurrent episodes of epistaxis led to the diagnosis of HHT. The patient was referred to the transplant center for liver transplantation due to the irreversible bleeding from the liver. Hepatic telangiectasias may be present in patients without hematologic disorders who have uncontrollable bleeding after liver biopsy.

Autoimmune manifestations associated with myelodysplastic syndrome predict a poor prognosis.

We evaluated the clinical characteristics of autoimmune manifestations (AIMs) associated with myelodysplastic syndrome (MDS) to elucidate whether AIMs impacted MDS outcomes in Japan.This retrospective study including 61 patients who received a new diagnosis of MDS between January 2008 and December 2015 was conducted by the review of electronic medical records for the presence of AIMs within a 1-year period prior to or following the diagnosis of MDS.AIMs were identified in 12 of the 61 (20.0%) patients with MDS. The neutrophil counts and C-reactive protein levels in peripheral blood were significantly elevated in patients with AIMs, and the survival was shorter in those with AIMs compared to those without AIMs. Multivariate analysis demonstrated that the presence of AIMs and higher-risk disease according to the International Prognositic Scoring System (IPSS) were independent risk factors for increased mortality (hazard ratio, 4.76 and 4.79, respectively).This retrospective study revealed that the prognosis was poor in patients with MDS-associated AIMs. The treatment of MDS using the current algorithms is based on prognostic scoring systems such as IPSS. Treatment strategies for patients with MDS-associated AIMs should be reconsidered, even in those with low-risk MDS according to the IPSS.

Myelodysplastic syndrome: Discordant involvement of the marrow as observed in the bone marrow biopsy sections

Myelodysplastic syndromes (MDS) are a diverse group of hematological disorders that affect the blood and bone marrow. Laboratory diagnosis of MDS is almost exclusively based on the morphology of hematopoietic cells observed in smears of peripheral blood and bone marrow and this depends solely on the presence of dysplastic changes observed in the granuloid, erythroid, and megakaryocytic cells [1,2]. Up until now evaluation of sections of bone marrow trephine biopsy specimen did not play a significant role in its diagnosis.

Systemic Pulmonary Events Associated with Myelodysplastic Syndromes: A Retrospective Multicentre Study.

Although pulmonary events are considered to be frequently associated with malignant haemopathies, they have been sparsely studied in the specific context of myelodysplastic syndromes (MDS). We aimed to describe their different types, their relative proportions and their relative effects on overall survival (OS). We conducted a multicentre retrospective cohort study. Patients with MDS (diagnosed according to the 2016 WHO classification) and pulmonary events were included. The inclusion period was 1 January 2007 to 31 December 2017 and patients were monitored until August 2019. Fifty-five hospitalized patients were included in the analysis. They had 113 separate pulmonary events. Thirteen patients (23.6%) had a systemic autoimmune disease associated with MDS. Median age at diagnosis of MDS was 77 years. Median time to onset of pulmonary events was 13 months. Pulmonary events comprised: 70 infectious diseases (62%); 27 interstitial lung diseases (23.9%), including 13 non-specific interstitial pneumonias and seven secondary organizing pneumonias or respiratory bronchiolitis–interstitial lung diseases; 10 pleural effusions (8.8%), including four cases of chronic organizing pleuritis with exudative effusion; and six pulmonary hypertensions (5.3%). The median OS of the cohort was 29 months after MDS diagnosis but OS was only 10 months after a pulmonary event. The OS was similar to that of the general myelodysplastic population. However, the occurrence of a pulmonary event appeared to be either an accelerating factor of death or an indicator for the worsening of the underlying MDS in our study. More than a third of pulmonary events were non-infectious and could be systemic manifestations of MDS.

Comorbidities and malignancies negatively affect survival in myelodysplastic syndromes: a population-based study

AbstractPopulation-based studies that contain detailed clinical data on patients with myelodysplastic syndrome (MDS) are scarce. This study focused on the real-world overall survival (OS) of MDS patients in association with comorbidities, specifically malignancies. An observational population-based study using the HemoBase registry was performed, including all patients with MDS diagnosed between 2005 and 2017 in Friesland, a Dutch province. Detailed information about diagnosis, patient characteristics, previous treatment of malignancies, and comorbidities according to the Charlson Comorbidity Index (CCI) was collected from electronic health records. Patients were followed up until June 2019. Kaplan-Meier plots and Cox regression analyses were used to study survival differences. In the 291 patients diagnosed with MDS, the median OS was 25.3 months (95% confidence interval [CI], 20.3-30.2). OS was significantly better for patients with CCI score <4, age <65 years, female sex, and low-risk MDS. Fifty-seven patients (20%) had encountered a prior malignancy (excluding nonmelanoma skin cancer), and a majority (38 patients; 67%) were therapy related. Both therapy-related and secondary MDSs were associated with worse OS (hazard ratio, 1.51; 95% CI, 1.02-2.23 and 1.58; 95% CI, 0.95-2.65, respectively), as compared with de novo MDS patients (P = .04). Patients in remission at time of MDS diagnosis had a similar median OS compared with patients with de novo MDS (25.5 vs 28.3 months). This population-based study involving all newly diagnosed MDS patients over a 13-year period in Friesland showed that multiple comorbidities, including previous malignancies, are associated with shorter OS. OS was not related to the use of radiotherapy or chemotherapy.

Myelodysplastic syndrome with t(6;9)(p22;q34.1)/DEK-NUP214 better classified as acute myeloid leukemia? A multicenter study of 107 cases.

t(6;9)(p22;q34.1)/DEK-NUP214 is a recurrent genetic abnormality that occurs in 1-2% of patients with acute myeloid leukemia (AML), and rarely in myelodysplastic syndrome (MDS). It has been suggested by others that all myeloid neoplasms with t(6;9)/DEK-NUP214 may be considered as AML, even when blast count is <20%. In this study, we compared the clinicopathologic features of 107 patients with myeloid neoplasms harboring t(6;9)/DEK-NUP214: 33 MDS and 74 AML. Compared with patients with AML, patients with MDS were older (p = 0.10), had a lower white blood cell count (p = 0.0017), a lower blast count in the peripheral blood (p < 0.0001) and bone marrow (p < 0.0001), a higher platelet count (p = 0.022), and a lower frequency of FLT3-ITD mutation (p = 0.01). In addition, basophilia was not a common feature in the patients of this cohort. Although there was no difference in overall survival between MDS and AML patients (p = 0.18) in the entire cohort, the survival curves did show a trend toward favorable survival in MDS patients. Multivariate analyses showed that initial diagnosis of MDS vs. AML and allogeneic hematopoietic stem cell transplantation were prognostic factors for survival of patients with t(6;9)/DEK-NUP214 (p = 0.008 and p < 0.0001, respectively). Our data suggest that MDS with t(6;9)/DEK-NUP214 is prognostically not equivalent to AML with t(6;9)/DEK-NUP214. These data also show that stem cell transplantation greatly improves the survival of MDS and AML patients with myeloid neoplasms associated with t(6;9)/DEK-NUP214.

The relationship between red cell distribution width and prognostic scores in myelodysplastic syndrome

IntroductionThe myelodysplastic syndrome (MDS) represents a group of hematopoietic neoplasms that is characterized by clonal hematopoiesis, cytopenia and abnormal cellular maturation. Red cell distribution width (RDW) refers to the variation degree of erythrocyte size and it is a reflection of anisocytosis. Higher values have been linked to adverse outcomes, such as increased mortality, vascular events, kidney and liver disease and demonstrated to harbor poor prognosis in solid and hematological malignancies. The RDW value can be used as a contributing parameter for MDS diagnosis, as well as its prognosis. In this study, we essentially aimed to demonstrate the correlation between the RDW and MDS prognostic indexes. Materials and methodsNinety-four MDS patients at the Aydın Adnan Menderes University Hematology Division were included in the study. The correlations between the RDW and laboratory values (either lactate dehydrogenase, albumin, globulin or ferritin) and the RDW prognostic scoring indexes (IPSS, WPSS, IPSS-R and LR-PSS) were investigated. The PASW for Windows, version 21.0 (SPSS Inc., Chicago, IL, USA), was used for statistical assessment. A p-value below 0.05 was the cut-off for the statistical significance. ResultsThe mean age of all the patients was 73 ± 10 years. Patients were observed for 41.88 ± 25 months. The mean RDW value for all cases was 15.5 ± 2.39. We found a statistically significant difference of survival between RDW values below and above 15.5% (p = 0.016). A significant difference was also observed according to the prognostic scoring indexes (see below). ConclusionAn increase in RDW is probably related to dysplasia in the MDS and this constitutes a possible explanation for the poor outcome. Prognostic indexes might incorporate the RDW as a parameter in the future.

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

Myelodysplastic 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.

Charlson comorbidity index predicts outcomes of elderly after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative therapy for acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), but advanced age with multiple comorbidities limits the eligibility for allo-HSCT. We conducted a retrospective study to investigate the comorbidities assessments and prognostic factors that predict outcomes for these patients. Clinical data of patients older than 50 years who had received diagnoses of AML or MDS and underwent allo-HSCT were obtained. Information on patient characteristics, including age, gender, allogeneic transplant type, conditioning regimens, Charlson comorbidity index (CCI), and presence of acute graft-versus-host disease (GVHD) or chronic GVHD, were collected and analyzed. Two hundred fifty-five elderly patients with a median age at allo-HSCT of 57 years were included. The significant prognostic factors associated with worse overall survival (OS) were CCI ≥3 (hazard ratio: 1.88) and grade III-IV acute GVHD (3.18). Similar findings were noted in the non-relapse mortality analysis. To investigate the effects of chronic GVHD on patient outcomes, OS analysis was performed for those with survival >100 days after transplantation. The results revealed CCI ≥3 (1.88) and grade III-IV acute GVHD (2.73) remained poor prognostic factors for OS, whereas mild chronic GVHD (0.43) was associated with better OS. This cohort study suggests that CCI ≥3 predicts poor outcomes, primarily due to a higher NRM risk. Careful management of GVHD after transplantation could improve outcomes in elderly patients with AML or MDS after allo-HSCT.

Trizomi 5 ve Trizomi 8'li İki Çocukta Pre-B Akut Lenfoblastik Lösemiye İlerleyen Çocukluk Çağı Miyelodisplastik Sendromu

Myelodysplastic syndrome (MDS) is a rare disorder in childhood. It is often characterized by cytopenias, morphological dysplastic changes, functional abnormalities in hematopoietic cells, and an increased risk for acute myeloid leukemia (AML). Transformation of MDS into AML can often be seen, but the transformation into acute lymphoblastic leukemia (ALL) is extremely rare in childhood. Previously only a few cases have been reported in the literature. In this article, we presented a 7-year-old female patient with trisomy 5 cytogenetic abnormality who developed ALL 9 months after the diagnosis of MDS, and a 6-year-old female patient with trisomy 8 cytogenetic abnormality who developed ALL 4 months after the diagnosis of MDS.

Persistence to hypomethylating agents and clinical and economic outcomes among patients with myelodysplastic syndromes

ABSTRACT Objectives To evaluate hypomethylating agent (HMA) persistence in patients with myelodysplastic syndromes (MDS), and examine its association with healthcare resource utilization (HRU) and progression to acute myeloid leukemia (AML). Methods A total of 2,400 adults diagnosed with MDS initiating HMAs were included from IBM MarketScan databases during 1/1/2011–3/31/2018. The index date was HMA initiation following MDS diagnosis. Patients were classified according to their persistence status by the end of a fixed ‘landmark period’ of 4 months post-index. Results Median persistence to HMAs was 5.6 months (95% CI: 5.2, 6.1); HMA non-persistence increased with time. Non-persistent patients had a significantly higher non-HMA-related HRU burden than persistent patients [adjusted incidence rate ratios, outpatient visits: 1.12 (95% CI: 1.10, 1.14); inpatient visits: 1.48 (95% CI: 1.30, 1.69); emergency department visits 1.30 (95% CI: 1.12, 1.50); all p-values < 0.001]. All-cause and HMA-related outpatient visits were lower among non-persistent patients, likely because of fewer HMA administration-related visits. The incidence rate of AML was numerically, although not significantly, higher in non-persistent patients, when starting follow-up at the end of the landmark period. When follow-up began at the index date, non-persistent patients had a significantly higher rate of AML [adjusted hazard ratio, 1.88 (95% CI: 1.53, 2.32); p-value < 0.001]. Conclusions HMA non-persistence, which increased over time, was associated with significantly higher non-HMA-related HRU, and numerically higher AML progression in MDS patients initiating HMAs. Future studies should evaluate predictors of HMA non-persistence in this patient population.

Incorporation of somatic panels for the detection of haematopoietic transformation in children and young adults with leukaemia predisposition syndromes and with acquired cytopenias.

Detection of somatic mutations may help verify the diagnosis of myelodysplastic syndrome (MDS) in patients with persistent cytopenias or with MDS-predisposition syndromes, prior to the development of overt leukemia. However, the spectrum and consequences of acquired changes in paediatric patients have not been fully evaluated, and especially not in the context of an underlying syndrome. We incorporated a targeted next-generation-sequencing panel of 54 genes for the detection of somatic mutations in paediatric and young adult patients with inherited or acquired cytopenias. Sixty-five patients were included in this study, of whom 17 (26%) had somatic mutations. We detected somatic mutations in 20% of individuals with inherited MDS-predisposition syndromes, including in patients with severe congenital neutropenia and Fanconi anaemia, and with germline mutations in SAMD9L. Thirty-eight per cent of children with acquired cytopenias and suspected MDS had somatic changes, most commonly in genes related to signal transduction and transcription. Molecularly abnormal clones often preceded cytogenetic changes. Thus, routine performance of somatic panels can establish the diagnosis of MDS and determine the optimal timing of haematopoietic stem cell transplantation, prior to the development of leukaemia. In addition, performing somatic panels in patients with inherited MDS-predisposition syndromes may reveal their unique spectrum of acquired mutations.

Exploring blast composition in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms: CD45RA and CD371 improve diagnostic value of flow cytometry through assessment of myeloblast heterogeneity and stem cell aberrancy.

BackgroundFlow cytometry immunophenotyping (FCIP) can improve diagnosis of myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN), although its application is challenging due to difficulties in standardization, complexity of antibody panels and subjective interpretation of data. Since blasts are invariably affected in these disorders, we developed a FCIP approach for detailed and objective analysis of the blast population.MethodsFCIP using a one‐tube 10‐color (13‐marker) antibody panel was performed on bone marrow samples from 23 MDS and 8 MDS/MPN patients, 21 cytopenic patients non‐diagnostic for MDS (Non‐MDS), and 16 Control samples.ResultsMDS and MDS/MPN cases demonstrated one to several immunophenotypic abnormalities including: increased myeloblasts, decreased stage‐1 hematogones, aberrant stem cells, abnormal myeloblast heterogeneity/divergence from normal, increased or decreased CD45 intensity, increased CD117 or CD123 intensity, decreased CD38 intensity, and aberrant expression of lineage markers (CD5, CD19, CD56). A Blast score was developed that showed sensitivity of 80.6% and specificity of 90.5% for immunophenotypic diagnosis of MDS and MDS/MPN. Expression levels of CD45RA and CD371 were used to evaluate abnormal myeloblast heterogeneity and stem cell aberrancy. Both these features were, for the first time, incorporated into a scoring system and resulted in 19% increase in the sensitivity of the assay for lower‐risk MDS.ConclusionDeep immunophenotypic analysis of the blast population is valuable for diagnosis of MDS and MDS/MPN and can potentially provide sensitivity and specificity figures comparable to those previously described using more comprehensive panels that assess maturing myelomonocytic and erythroid elements in addition to progenitor cells.

Some characteristics of patients with myelodysplastic syndrome

Objective: epidemiological analysis of myelodysplastic syndrome, based on the available retrospective data.Materials and methods: a retrospective analysis of the medical history data of 115 patients (61 men and 54 women) with a diagnosis of myelodysplastic syndrome who received treatment in the hematology department of the «City Hospital № 7 of the city of Rostov-on-Don» in the period from 2010 to 2019.Results: the most likely comorbidities were cardiovascular diseases, which are the main cause of sudden death, and endocrine diseases, which together influence the outcome of myelodysplastic syndrome.Conclusions: there are no individual risk assessment algorithms that could determine the goal setting of therapy in patients with myelodysplastic syndrome, whose life expectancy depends more on the course of concomitant diseases.