Do we Need to Perform Bone Marrow Examination in all Subjects Suspected of MDS? Evaluation and Validation of Non-Invasive (Web-Based) Diagnostic Algorithm.

Background: Bone marrow examination (BME) is the gold standard of diagnosing myelodysplastic syndromes (MDS).

Problems: it is invasive, painful, causing possible bleeding, inaccurate (aspirate hemodilution), and subjective (inter-observer interpretation discordance). We developed non-invasive diagnostic tools: A logistic regression formula [LeukRes 2018], then a web algorithm using 10 variables (age, gender, Hb, MCV, WBC, ANC, monocytes, PLT, glucose, creatinine) to diagnose/exclude MDS [BldAdv 2021].

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.

How we diagnose Myelodysplastic syndromes.

The Myelodysplastic syndromes (MDS) are a heterogenous group of clonal bone marrow (BM) stem cell myeloid neoplasms, characterized by ineffective hematopoiesis that results in dysplasia in hematopoietic cells and peripheral cytopenias, especially anemia, and a propensity to leukemic transformation. The suspicion of MDS is raised by a typical but not specific clinical picture and routine laboratory findings, but the gold standard for MDS diagnosis is still BM examination with the presence of uni-or multi-lineage dysplasia and increased blast percentage, together with exclusion of other reasons. Cytogenetics is also an essential part of the diagnostic and prognostic processes.

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

Introduction: 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.

Methods: 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.

MDS-Related Anemia Is Associated with Impaired Quality of Life but Improvement Is Not Always Achieved by Increased Hemoglobin Level.

Quality of life is impaired in MDS, but the role of hemoglobin level is unclear. To study the Hb-QoL correlation at diagnosis and 1 year later, patients filled out the EQ-5D questionnaire, assessing their mobility, self care, daily activities, pain/discomfort, and anxiety/depression, using scores of 0 (normal), 1 (mild/moderate), or 2 (poor). They also evaluated their health using a visual analogue scale, scoring from 0 (poor) to 100 (excellent).

Lymphoid aggregates in the bone marrow biopsies of patients with myelodysplastic syndromes - A potential prognostic marker?

Background: Lymphoid aggregates (LA) are occasionally seen in bone marrow biopsies (BMB) of myelodysplastic syndromes (MDS) patients. Our aim was to evaluate their incidence and association with prognosis.

Methods: We compared BMB reports of MDS patients treated at the Tel Aviv Sourasky Medical Center (2011-2018), and controls (2015-2017, normal BMB), and examined the charts of the MDS patients (LA+ and LA-).

Serum Hypoalbuminemia Is a Long-Term Prognostic Marker in Medical Hospitalized Patients, Irrespective of the Underlying Disease.

Hypoalbuminemia is common in hypoalbuminemia-associated disorders (HAD), e.g., liver and kidney disease.

Effectiveness of the BNT162b2mRNA COVID-19 vaccine in patients with hematological neoplasms in a nationwide mass vaccination setting.

Evidence regarding the effectiveness of COVID-19 vaccine in patients with impaired immunity is limited. Initial observations suggest a lower humoral response in these patients. We evaluated the relative effectiveness of the mRNA BNT162b2 vaccine in patients with hematological neoplasms compared with matched controls.

Unraveling a Nosocomial Outbreak of COVID-19: The Role of Whole-Genome Sequence Analysis.

Background: The coronavirus disease 2019 (COVID-19) pandemic poses many epidemiological challenges. The investigation of nosocomial transmission is usually performed via thorough investigation of an index case and subsequent contact tracing. Notably, this approach has a subjective component, and there is accumulating evidence that whole-genome sequencing of the virus may provide more objective insight.

A predictive algorithm using clinical and laboratory parameters may assist in ruling out and in diagnosing MDS.

We present a noninvasive Web-based app to help exclude or diagnose myelodysplastic syndrome (MDS), a bone marrow (BM) disorder with cytopenias and leukemic risk, diagnosed by BM examination. A sample of 502 MDS patients from the European MDS (EUMDS) registry (n > 2600) was combined with 502 controls (all BM proven). Gradient-boosted models (GBMs) were used to predict/exclude MDS using demographic, clinical, and laboratory variables.

Anti-CD20-Mediated B Cell Depletion Is Associated With Bone Preservation in Lymphoma Patients and Bone Mass Increase in Mice.

Immunotherapy with anti-CD20-specific antibodies (rituximab), has become the standard of care for B cell lymphoproliferative disorders and many autoimmune diseases. In rheumatological patients the effect of rituximab on bone mass yielded conflicting results, while in lymphoma patients it has not yet been described. Here, we used cross-sectional X-ray imaging (CT/PET-CT) to serially assess bone density in patients with follicular lymphoma receiving rituximab maintenance therapy.

Erythropoietin receptor in B cells plays a role in bone remodeling in mice.

Erythropoietin (EPO) is a key regulator of erythropoiesis. However, EPO receptors (EPO-Rs) are also expressed on non-erythroid cell types, including myeloid and bone cells. Immune cells also participate in bone homeostasis.

Erythropoietin Treatment Is Associated with Decreased Blood Glucose Levels in Hematologic Patients.

Background: Erythroid stimulating agents (ESAs) have pleiotropic effects, and in animal and human studies those exposed to high erythropoietin had lower blood glucose.

Objective: To determine the association between ESA and glucose in anemia-treated patients with myelodysplastic syndromes (MDS) or multiple myeloma (MM).

Patients And Methods: Patients' glucose levels were compared while on to while off ESA, and all served as their own controls.

Kinetics of pre-myelodysplastic syndromes blood values correlate with disease risk and survival.

We reviewed pre-diagnosis clinical data of 420 patients with pathologically confirmed myelodysplastic syndromes (MDSs) presenting with anemia. In 232 patients with yearly pre-diagnosis complete blood counts (CBCs), we also analyzed CBC kinetics in respects to a standardized timepoint in which all patients had similar levels of hemoglobin (Hgb). At the standardized timepoint (last documented 12 > Hgb ≥ 11 g/dL), occurring months-years before diagnosis, median CBC values were Hgb 11.

Erythropoietin Mediated Bone Loss in Mice Is Dose-Dependent and Mostly Irreversible.

Recent studies have demonstrated that erythropoietin (EPO) treatment in mice results in trabecular bone loss. Here, we investigated the dose-response relationship between EPO, hemoglobin (Hgb) and bone loss and examined the reversibility of EPO-induced damage. Increasing doses of EPO over two weeks led to a dose-dependent increase in Hgb in young female mice, accompanied by a disproportionate decrease in trabecular bone mass measured by micro-CT (µCT).

Myelodysplastic Syndromes Over Time: A Comparison of Two Patient Cohorts.

Background: With advances in myelodysplastic syndromes (MDS), patient cohorts from different time periods might be different.

Objectives: To compare presentation and outcomes between two cohorts.

Methods: Data were collected from George Washington University Medical Center, Washington, DC, USA 1986-1987 (DC), and Tel Aviv Medical Center, Israel 1999-2009 (TA).

Thrombocytopenia in Patients with Myelodysplastic Syndromes: Still an Unsolved Problem.

The myelodysplastic syndromes (MDS) are a group of clonal bone marrow (BM) stem cell disorders, characterized by ineffective hematopoiesis, peripheral cytopenias, and hematologic cellular dysfunction, as well as potential transformation to acute leukemia. Thrombocytopenia is common in MDS and is associated with bleeding complications, occasionally life-threatening. Low platelet count (PLT), as well declining PLT also serves as a prognostic marker.

Can bone marrow cellularity help in predicting prognosis in myelodysplastic syndromes?

Objectives: To ascertain the relevance of bone marrow cellularity (BMC) to the interpretation of blast percentage (blast%) in MDS prognostication.

Methods: We compared survival prediction based on blast% adjusted to different levels of cellularity, compared to the survival based on the original IPSS-R blast% grouping.

Results: We analyzed 355 consecutive MDS patients.

Is bone marrow examination always necessary to establish the diagnosis of myelodysplastic syndromes? A proposed non-invasive diagnostic model.

A non-invasive myelodysplastic syndromes (MDS) diagnostic model would allow for care while avoiding invasive bone marrow examinations (BME). BME-established MDS patients were compared to non-MDS (BME-excluded) patients. Variables (gender, age, hemoglobin (Hb), mean red blood cell corpuscular volume (MCV), platelet (PLT), and white blood cell (WBC)) were combined with multivariate logistic regression; a probability score (Y) was calculated.

Erythropoietin administration is associated with improved T-cell properties in patients with myelodysplastic syndromes.

The immune system is impaired in myelodysplastic syndromes (MDS) and plays a role in the pathogenesis of the disease. Here we show effects of recombinant human erythropoietin (rHuEPO) on T cell (CD4, CD8 and CD4CD25) number and function in MDS patients. Healthy (20 subjects), MDS patients without rHuEPO treatment ('MDS', 13), and MDS patients treated with rHuEPO ('MDS+EPO', 17) were examined.

Azacitidine-lenalidomide (ViLen) combination yields a high response rate in higher risk myelodysplastic syndromes (MDS)-ViLen-01 protocol.

Azacitidine treatment is effective in higher risk MDS (HR-MDS), with less than 50 % response, lasting 2 years. Aza and lenalidomide (Len) have a potential synergistic effect. ViLen-01 phase IIa trial includes 6-month induction (Aza 75 mg/m(2)/day, days 1-5, Len 10 mg/day, days 6-21, every 28 days), 6-month consolidation (Aza 75 mg/m(2)/day, days 1-5, every 28 days), and 12-month maintenance (Len 10 mg/day, days 1-21, every 28 days).