Diagnosis Of Myelodysplastic Syndrome Research Articles

Diagnosis of myelodysplastic syndromes: the classic and the novel.

The Myelodysplastic syndromes (MDS) are a heterogenous group of clonal bone marrow (BM) stem cell myeloid neoplasms, characterized by bone marrow (BM) dysplasia, macrocytic anemia or cytopenia with a tendency for leukemic transformation. The suspicion of MDS is raised by a typical but not specific clinical picture and routine labs, but the gold standard for MDS diagnosis is still BM examination with the presence of uni-or multi-lineage dysplasia and blast percentage, together with exclusion of other reasons. Cytogenetics is also a part of the diagnostic process. Flow cytometry and genetics are helpful but are not always mandatory for MDS diagnosis. This review summarizes the current steps in the diagnostic approach for a patient suspected of having MDS. We also describe new concepts that use non-invasive diagnostic technologies, especially digital methods as well as peripheral blood genetics. The hope is that one day these will mature, be introduced into clinical practice, and perhaps in many cases even replace the invasive BM biopsy.

Pediatric Myelodysplastic Syndrome.

Myelodysplastic syndromes (MDSs) are rare in children and have unique clinical manifestations and implications. To review the clinical features, pathogenesis, and classification of pediatric MDS. Published literature and personal experience. Pediatric MDS vastly differs from adult MDS. Evaluation for the presence of an underlying germline predisposition syndrome is critical for optimal classification and management. Because of the rarity of cases, resources to aid with the recognition, diagnosis, and management of pediatric MDS are limited, and multi-institutional collaborative studies are needed for the future.

Efficient and novel multidomain feature analysis model with incremental optimizations for enhancing pediatric myelodysplastic syndrome detection

Pediatric myelodysplastic syndromes (MDS) are complicated, thus early and accurate diagnosis is essential for treatment planning and patient care. Diagnostic processes often use discrete data domain analysis, which reduces accuracy and delays diagnosis. This work addresses these limitations by introducing an advanced Multi domain Feature Analysis Model (MFAM) enhanced with incremental optimizations to improve pediatric MDS detection. Traditional pediatric MDS diagnosis relies on subjective evaluations and limited data fusion, not modern computational methods. These constraints may reduce diagnosis accuracy and postpone action. The proposed MFAM integrates data from Clinical History, Physical Examination, Blood Cell Counts, Peripheral Blood Smear, Bone Marrow Aspiration and Biopsy, Cytogenetic Analysis, Flow Cytometry, Genetic Testing, Iron Studies, and Bone Marrow Cytology to overcome these challenges. The MFAM increases feature variance by fusing Bidirectional Long Short-Term Memory (BiLSTM) with Bidirectional Gated Recurrent Units (BiGRU). Deep Q Learning with Graph Recurrent Convolutional Neural Networks (DQGRCNN) boosts efficiency. Additionally, the model integrates the Vector Autoregressive Moving Average with Exogenous Inputs (VARMAX) to facilitate early prediction of paediatric MDS. These enhancements have resulted in significant improvements in the precision of paediatric MDS detection by 4.5%, accuracy by 3.5%, recall by 2.3%, Area Under the Curve (AUC) by 1.5%, and specificity by 2.4% while reducing diagnostic delays by 8.5%. Furthermore, the model enhances the precision of predictive analysis by 2.9%, accuracy by 3.5%, recall by 2.5%, AUC by 2.9%, specificity by 5.5%, and reduces delays in predictive analysis by 8.5%. The MFAM presented in this paper revolutionizes the diagnosis and treatment of paediatric MDS by efficiently combining diverse diagnostic data, employing advanced transformation and fusion techniques, and optimizing responses through DQGRCNN. The integration of VARMAX further enables early prediction of the disease. MFAM will enhance diagnostic precision, therapy start, and clinical outcomes for young MDS patients.

MDS patient registries - achievements and challenges.

Since the late 1980s, patient registries have played a pivotal role in the elucidation of rare diseases. For myelodysplastic syndromes (MDS), they revealed the disease actually to be diverse rather than rare. Registry data enabled the definition of various MDS subtypes and prognostic scores tailoring therapy. These classifications have been revised and refined several times, and the differential diagnosis of MDS has become increasingly complex. At the same time, the diagnosis has been made more commonly and no longer by specialized centers of expertise only. Consequently, several registries have collected data with different focuses and from different patient subpopulations. The current review presents three MDS registries and their rationale, scope, design, and achievements. All three complement each other and will remain a mainstay to advance the knowledge on MDS as well as to validate the outcomes of clinical trials. However, delineation of subtypes after the most recent WHO and IPC revisions, as well as the determination of the newest risk score M of the International Prognostic Scoring System (IPSS-M), no longer just shift cut-offs but are based on multivariate compilations of highly specific genetic information. This paradigm shift involves challenging registries with respect to the assignment of all patients for whom this information has not yet been available.

Kidney involvement in myelodysplastic syndromes.

The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9g/g, and median serum creatinine was 3.2mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.

A case of destination therapy for post-fulminant myocarditis with myelodysplastic syndrome.

We encountered a 64-year-old woman who experienced fulminant myocarditis and underwent treatment with veno-arterial extracorporeal membrane oxygenation and Impella CP support. Subsequently, she underwent a device upgrade to Impella 5.5 and received continuous hemodiafiltration for 3 months. During mechanical circulatory support, she developed refractory anemia and thrombocytopenia, leading to a diagnosis of myelodysplastic syndrome. Following the removal of the devices, she no longer required blood transfusions. She received HeartMate 3 left ventricular assist device implantation as a destination therapy indication despite the presence of myelodysplastic syndrome. She was successfully managed by aspirin-free antithrombotic therapy without any hemocompatibility-related adverse events for 4 months after index discharge on foot. We present a patient with a unique and rare presentation, wherein HeartMate 3 was implanted and successfully managed without aspirin to prevent bleeding complications associated with myelodysplastic syndrome.

Impact of frailty on patients hospitalized with myelodysplastic syndrome: A nationwide analysis.

6569 Background: Myelodysplastic Syndrome (MDS) is a complex group of neoplasms that arises from abnormalities in the bone marrow's hematopoietic stem cells, leading to ineffective blood cell production. Frailty signifies increased vulnerability to internal and external stressors, with its impact on survival in MDS gaining recognition. We conducted a retrospective analysis to explore the impact of frailty on hospitalized MDS patients and its association with unfavorable hospital outcomes. Methods: National Inpatient Sample (NIS) 2019 and 2020 was utilized to identify the patients admitted with a primary diagnosis of MDS and had a concurrent diagnosis of Frailty. The Primary outcome was Mortality, and secondary outcomes included length of stay, total cost of hospitalization, and other adverse in-hospital outcomes. Multivariate logistic regression analysis was used to calculate the outcomes after adjusting for baseline sociodemographic characteristics. Results: A total of 17,000 patients were admitted with a primary diagnosis of MDS, among whom 4,285 (25.20%) patients had a concurrent diagnosis of Frailty. The mean age of patients with and without Frailty was 75.75 (+/-14.01) and 71.54 (+/-14.68), respectively, p<0.001. After adjusting for confounding variables, Frailty was considered an independent predictor of mortality in MDS patients (OR=1.80 (1.22-2.64); p=0.003). Patients with Frailty had a prolonged length of stay in the hospital (8.62 days(3.2-9.6) without and 11.56 days (4.6-12.1) with Frailty, P<0.001), as well as an increased total cost of hospitalization ($ 132159 (3256-23651) without and $173898 (5317-389146) with Frailty, p<0.001). Additionally, Frailty was associated with an increased likelihood of sepsis (OR=2.02 (1.33-3.06); p=0.001), acute kidney injury (OR=1.22 (1.02-1.50); p=0.04), major depressive disorder (OR=1.51 (1.19-1.91); p=0.001), and a higher association with chemotherapy (OR=3.46 (1.21-9.91); p=0.021) and palliative care (OR=2.23 (1.72-2.90); p<0.001). However, frail patients were less likely to receive blood transfusions (OR=0.73 (0.61-0.88); p=0.001), and no difference was noted in the risk of platelet transfusions (OR=0.95 (0.73-1.25); p=0.763). Conclusions: Frailty is considered an independent predictor of mortality and is associated with increased healthcare resource utilization along with other adverse in-hospital outcomes. Careful and thorough identification of frailty and its effective management is crucial for improving outcomes, reducing mortality, and enhancing the quality of life for patients with debilitating MDS. [Table: see text]

Precision diagnosis of myelodysplastic syndromes using integrated genomic and clinical data: A machine learning approach

Precision diagnosis of myelodysplastic syndromes using integrated genomic and clinical data: A machine learning approach

Unveiling the Variances: Myelodysplastic Syndrome (MDS) Patient Admissions in Teaching vs Nonteaching Hospitals

Background We have carried out an analysis to evaluate the influence of hospital teaching status on the outcomes of individuals hospitalized with MDS. Methods The National Inpatient Sample (NIS) dataset for the years 2019-2020 was employed to identify individuals who were hospitalized with a primary diagnosis of MDS. These patients were then categorized into two groups: those who were hospitalized in teaching hospitals and those who were hospitalized in non-teaching hospitals. Multivariate regression analysis was performed to calculate the primary and secondary outcomes. Results In the years 2019 and 2020, a total of 17,000 patients were hospitalized with myelodysplastic syndromes (MDS). Among these, 24.05% (4,080) were admitted to non-teaching hospitals, while 75.94% (12,920) were admitted to teaching hospitals. Patients admitted to teaching hospitals had a higher likelihood of mortality (OR 1.84, 95% CI 1.03-3.27, P=0.037), as well as increased lengths of stay (+3.58 Days, 95% CI 2.82-4.34, P<0.001)and total hospitalization costs (+USD 66818, 95% CI 50528-83108, P<0.001). Additionally, patients in teaching hospitals had a higher incidence of acute respiratory failure (6.81% vs 4.4%), acute kidney injury (23.89% vs 17.72%), hematopoietic stem cell transplantation (14.36% vs 0.61%), and febrile neutropenia (11.03% vs 5.86%). However, patients in teaching hospitals had a lower incidence of anemia (41.86% vs 48.53%) and blood transfusions (38.8% vs 55.37%). Conclusion Individuals who were admitted to teaching hospitals with Myelodysplastic Syndromes (MDS) exhibited a notably higher mortality rate, as well as an extended length of stay and a corresponding increase in the total cost of hospitalization. Patients in teaching hospitals were also at risk for acute kidney injury, acute respiratory failure and febrile neutropenia.

Potential Diagnostic Value of Abnormal Pyroptosis Genes Expression in Myelodysplastic Syndromes (MDS): A Primary Observational Cohort Study.

Background: Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice. Materials and Methods: In the present study, we evaluated the expression of genes that form the inflammasome (NLRP3, ASC, and CASP1) in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS. Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with p value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis. Results: We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with a p-value of 0.001 and 1.86 with p=0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with p=0.0001 for Caspase-1 and an AUC of 0.665 with p=0.0139 for ASC to MDS discrimination. Conclusion: Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested.

Comparison of cytomorphology and histomorphology in myelodysplastic syndromes.

Gold standard for the establishment of the diagnosis of myelodysplastic syndromes (MDS) are cytomorphological features of hematopoietic cells in peripheral blood and bone marrow aspirates. There is increasing evidence that bone marrow histomorphology not only aids in the diagnosis of MDS but can provide additional prognostic information, particularly through assessment of fibrosis and cellularity. However, there is only sparse data on direct comparison between histological and cytomorphological findings within the same MDS patient cohort. Therefore, we performed such an analysis under exceptionally well-standardized conditions. We reexamined biopsy material of 128 patients from the Düsseldorf MDS registry who underwent bone marrow trephine biopsy (in addition to bone marrow aspiration) at the time of diagnosis, addressing the following items: a. Analysis of concordance of diagnoses made by histology and cytomorphology b. Analysis of additional information by histology with regard to the diagnosis and prognosis. The respective biomaterials were available at our institution and had been processed according to unchanged protocols between 1992 and 2010. Fresh histopathological sections were obtained from the tissue blocks, stained under identical conditions and re-assessed by a designated expert pathologist (C.B.) without knowledge of the previous histopathological report or the respective cytomorphological diagnosis. The latter, likewise, was uniformly made by the same expert cytomorphologist (U.G.). Histopathology of bone marrow trephine biopsies reliably captured the diagnosis of MDS. Assignment to the diagnostic WHO subgroup was not entirely concordant with cytomorphology, mainly due to incongruences between the proportion of CD34-positive cells on histopathology and the cytomorphological blast count. Histopathology provided additional diagnostic and prognostic information with high diagnostic and prognostic significance, such as fibrosis. Likewise, histopathology allowed more reliable estimation of bone marrow cellularity.

Construction and experimental validation of a novel ferroptosis-related gene signature for myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by morphological abnormalities and peripheral blood cytopenias, carrying a risk of progression to acute myeloid leukemia. Although ferroptosis is a promising target for MDS treatment, the specific roles of ferroptosis-related genes (FRGs) in MDS diagnosis have not been elucidated. MDS-related microarray data were obtained from the Gene Expression Omnibus database. A comprehensive analysis of FRG expression levels in patients with MDS and controls was conducted, followed by the use of multiple machine learning methods to establish prediction models. The predictive ability of the optimal model was evaluated using nomogram analysis and an external data set. Functional analysis was applied to explore the underlying mechanisms. The mRNA levels of the model genes were verified in MDS clinical samples by quantitative real-time polymerase chain reaction (qRT-PCR). The extreme gradient boosting model demonstrated the best performance, leading to the identification of a panel of six signature genes: SREBF1, PTPN6, PARP9, MAP3K11, MDM4, and EZH2. Receiver operating characteristic curves indicated that the model exhibited high accuracy in predicting MDS diagnosis, with area under the curve values of 0.989 and 0.962 for the training and validation cohorts, respectively. Functional analysis revealed significant associations between these genes and the infiltrating immune cells. The expression levels of these genes were successfully verified in MDS clinical samples. Our study is the first to identify a novel model using FRGs to predict the risk of developing MDS. FRGs may be implicated in MDS pathogenesis through immune-related pathways. These findings highlight the intricate correlation between ferroptosis and MDS, offering insights that may aid in identifying potential therapeutic targets for this debilitating disorder.

Analyzing Blood Cells of High-Risk Myelodysplastic Syndrome Patients Using Interferometric Phase Microscopy and Fluorescent Flow Cytometry.

Myelodysplastic syndromes (MDSs) are a group of potentially deadly diseases that affect the morphology and function of neutrophils. Rapid diagnosis of MDS is crucial for the initiation of treatment that can vastly improve disease outcome. In this work, we present a new approach for detecting morphological differences between neutrophils isolated from blood samples of high-risk MDS patients and blood bank donors (BBDs). Using fluorescent flow cytometry, neutrophils were stained with 2',7'-dichlorofluorescin diacetate (DCF), which reacts with reactive oxygen species (ROS), and Hoechst, which binds to DNA. We observed that BBDs possessed two cell clusters (designated H and L), whereas MDS patients possessed a single cluster (L). Later, we used FACS to sort the H and the L cells and used interferometric phase microscopy (IPM) to image the cells without utilizing cell staining. IPM images showed that H cells are characterized by low optical path delay (OPD) in the nucleus relative to the cytoplasm, especially in cell vesicles containing ROS, whereas L cells are characterized by low OPD in the cytoplasm relative to the nucleus and no ROS-containing vesicles. Moreover, L cells present a higher average OPD and dry mass compared to H cells. When examining neutrophils from MDS patients and BBDs by IPM during flow, we identified ~20% of cells as H cells in BBDs in contrast to ~4% in MDS patients. These results indicate that IPM can be utilized for the diagnosis of complex hematological pathologies such as MDS.

The Lived Experience of Seeking Pregnancy in a Woman with a History of Cancer

Myelodysplastic syndromes (MDS) are a rare form of cancer that affects the bone marrow's ability to produce mature blood cells. Several treatments are available, including chemotherapy using anticancer or cytotoxic drugs, blood or platelet transfusions, and stem cell transplants. In this study, a 33-year-old woman shares her experience of attempting to conceive while undergoing treatment for myelodysplastic syndromes. The study aimed to explore the psychosocial difficulties women with a history of cancer treatment may encounter when trying to get pregnant. Semi-structured qualitative interviews were undertaken, recorded, and transcribed verbatim. The transcript was analyzed by narrative analysis. Four themes were identified: 1) Support from loved ones, 2) Challenges in conceiving, 3) Emotional ups and downs during pregnancy, and 4) The joy of motherhood. A cancer diagnosis can devastate young women, primarily if the treatment affects their fertility. These women must have the support of their husbands. Fortunately, many methods are available to assist women in successfully conceiving, although the journey can be difficult and emotional. The ups and downs of the process are inevitable, but the desire to become a mother makes it all worth it in the end. Cancer treatment for myelodysplastic syndromes and related conditions can profoundly impact childbearing women. Such women may face significant challenges if they plan to have a child after treatment. Hence, further research with more women with the diagnosis of MDS is imperative in this critical area.

A Pre-Leukemic DNA Methylation Signature in Healthy Individuals at Higher Risk for Developing Myeloid Malignancy.

DNA methylation alterations are widespread in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. Although the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory. We performed global DNA methylation profiling in a case control study nested within the Singapore Chinese Health Study to evaluate whether DNA methylation alterations were associated with AML/MDS development. Targeted deep sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-seq) were performed on peripheral blood collected a median of 9.9 years before diagnosis of AML or MDS, together with age-matched still-healthy individuals as controls. Sixty-six individuals who developed AML or MDS displayed significant DNA methylation changes in the peripheral blood compared with 167 age- and gender-matched controls who did not develop AML/MDS during the follow-up period. Alterations in methylation in the differentially methylation regions were associated with increased odds of developing AML/MDS. The epigenetic changes may be acquired independently and before somatic mutations that are relevant for AML/MDS development. The association between methylation changes and the risk of pre-AML/MDS in these individuals was considerably stronger than somatic mutations, suggesting that methylation changes could be used as biomarkers for pre-AML/MDS screening.

February 2024 Medical Image of the Month: Pulmonary Alveolar Proteinosis in Myelodysplastic Syndrome

No abstract available. Manuscript truncated after 150 words. Lymphadenopathy decreased after initiation of coccidiomycosis treatment, but symptoms and crazy paving findings continued to worsen. Further workup revealed a new diagnosis of myelodysplastic syndrome (MDS) and subsequent bronchoalveolar lavage (BAL) and histology results were consistent with secondary PAP, likely due to patient’s underlying hematologic disease. Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of lipoproteinaceous material in the lung alveoli. There are two types of PAP that occur in adults: Idiopathic/ autoimmune and Secondary PAP. Idiopathic/autoimmune PAP is more common and is thought to result from antibody production against granulocyte-macrophage-colony-stimulating factor (GM-CSF) that regulates surfactant homeostasis. Secondary PAP results from a precipitating condition, often inhalation exposure, underlying malignancy, or immunocompromise. The clinical manifestations of PAP are nonspecific and includes dyspnea, nonproductive cough, fatigue, and weight loss. CT may show nonspecific findings of smooth, bilateral interlobular septal thickening superimposed on a background of ground-glass opacification (crazy-paving). Diagnosis is confirmed with …

A flow cytometric approach to compare stem cell apoptosis in aplastic anemia and hypoplastic myelodysplastic syndrome.

Aplastic anemia (AA) is a disease caused by bone marrow (BM) failure. There are many similarities between AA and hypoplastic myelodysplastic syndrome (MDS); hence, differentiating them could be problematic. The current study aimed to use the new technique of flow cytometry as a possible diagnostic tool for AA and hypoplastic MDS. The BM mononuclear cell (BMMC) and blood samples from 44 participants (17 patients with AA, 13 with hypoplastic MDS, and 14 healthy controls) were collected. The flow cytometric analysis of the cluster of differentiation 34 (CD34) levels and cell apoptosis was performed for all sample types. Patients with hypoplastic MDS showed a high percentage of CD34+ cells with low apoptosis, while those with AA showed a low percentage of CD34+ cells with high apoptosis. Despite the similarity in the clinical presentation of hypoplastic MDS and AA, they are biologically different disorders. Increased CD34+ cell numbers with high viability may provide a useful and accurate tool for the differential diagnosis of hypoplastic MDS from AA.

Cutaneous manifestations of myelodysplastic syndrome: A systematic review.

Myelodysplastic syndrome (MDS) may present with specific skin lesions, such as leukaemia cutis, which is a well known poor prognostic marker of leukaemia with a high risk of acute leukaemic transformation. However, less is known regarding non-specific cutaneous manifestations of MDS including the prevalence, types and their prognostic and therapeutic significance, which we aimed to determine through this systematic review. We searched electronic databases (PubMed, Medline and EMBASE) from inception up to 26 January 2023 for studies reporting cutaneous manifestations of MDS. Eighty eight articles (case reports n=67, case series n=21), consisting of 134 patients were identified. We identified 6 common cutaneous manifestations: neutrophilic dermatoses (n=64), vasculitis (n=21), granulomatous (n=8), connective tissue disease (CTD) (n=7; composed of dermatomyositis (n=5), cutaneous lupus erythematosus (n=1), and systemic sclerosis (n=1)), panniculitis (n=4), immunobullous (n=1), and other (n=29). Cutaneous features either occurred at time of MDS diagnosis in 25.3%, preceding the diagnosis in 34.7% (range 0.5-216months), or after diagnosis in 40.0% (range 1-132months). Prognosis was poor (40.2% death) with 34.1% progressing to acute myeloid leukaemia (AML). 50% of those with MDS who progressed to AML had neutrophilic dermatoses (p=0.21). Myelodysplastic syndrome was fatal in 39.2% of neutrophilic dermatoses (median time from onset of cutaneous manifestation: 12months), 50% of vasculitis (7.5months), 62.5% of granulomatous (15.5months) and 14.3% of CTD (7months). Recognition of patterns of cutaneous features in MDS will improve early diagnosis and risk stratification according to subtype and associated prognosis.

Validation of a novel algorithm with a high specificity in ruling out MDS.

A previously published web-based App using Gradient-boosted models (GBMs) of eight laboratory parameters was established by Oster et al. to facilitate diagnosis or exclusion of myelodysplastic syndromes (MDS) in patients. To validate their algorithm, we compared 175 anemic patients with MDS diagnosis from our German MDS Registry with 1378 non-MDS anemic patients who consulted various specialties in the Düsseldorf university hospital. Based on hemoglobin level, leukocyte and platelet count, mean corpuscular volume, absolute neutrophil count, absolute monocyte count, glucose and creatinine, plus the patients' gender and age, we could not reproduce a high negative predictive value (NPV), but confirmed a useful specificity of 90.9% and a positive predictive value (PPV) of 77.1%. 1192 of 1378 controls were correctly categorized as "probably not MDS (pnMDS)" patients. A total of 65 patients were wrongly classified as "probable MDS (pMDS)," of whom 48 had alternative explanations for their altered laboratory results. In a second analysis, we included 29 patients with chronic myelomonocytic leukemia (CMML) resulting in only one label as possible MDS, suggesting that highly proliferative bone marrow disorders are correctly excluded. The possibility of reliably excluding MDS from differential diagnosis based on peripheral blood lab work appears to be attractive for patients and physicians alike while the confirmation of MDS diagnosis still requires a bone marrow biopsy.

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.