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.

Infectious Complications in Patients with Myelodysplastic Syndromes: A Report from the Düsseldorf MDS Registry.

Despite notable advancements in infection prevention and treatment, individuals with hematologic malignancies still face the persistent threat of frequent and life-threatening complications. Those undergoing chemotherapy or other disease-modifying therapies are particularly vulnerable to developing infectious complications, increasing the risk of mortality. Myelodysplastic syndromes (MDS) predominantly affect the elderly, with the incidence rising with age and peaking at around 70 years.

Influence of platelet count at diagnosis and during the course of disease on prognosis in MDS patients.

Thrombocytopenia at diagnosis and platelet drop within the first 6 months have an adverse effect on prognosis of MDS patients. We therefore were interested in the association and impact on prognosis of morphologic findings of megakaryocytes and platelets with platelet count at diagnosis, bleeding complications, and the drop of platelets during the course of disease. This retrospective analysis was based on 334 MDS patients from the Duesseldorf MDS registry that were followed up for blood counts, bleeding, transfusion dependency, and AML evolution and correlated with morphology of the megakaryocytes and platelets.

Eligibility for clinical trials is unsatisfactory for patients with myelodysplastic syndromes, even at a tertiary referral center.

Participation in clinical trials may allow patients with MDS to gain access to therapies not otherwise available. However, access is limited by strict inclusion and exclusion criteria, reflecting academic or regulatory questions addressed by the respective studies. We performed a simulation in order to estimate the average proportion of MDS patients eligible for participation in a clinical trial.

Comprehensive analysis of isolated der(1;7)(q10;p10) in a large international homogenous cohort of patients with myelodysplastic syndromes.

The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the new comprehensive cytogenetic scoring system for MDS, chromosome 7 anomalies are no longer generally assigned to poor risk features but are thoroughly separated. However, der(1;7)(q10;p10), hereinafter der(1;7), is merged into the group labeled "any other single" and belongs to the intermediate risk group, just by definition due to lack of adequate clinical data.

Additional prognostic impact of the percentage of erythroid cells in the bone marrow of patients with myelodysplastic syndromes.

In patients with myelodysplastic syndromes (MDS) the impact of the percentage of erythroid precursors in the bone marrow has been the subject of considerable debate, especially with regard to prognosis. We examined the prognostic impact of the percentage of erythroid cells in the bone marrow (bmery) in 2453 primary untreated MDS patients in a retrospective multi-center analysis. Bmery were quantified in bone marrow smears at the time of diagnosis and were correlated with overall survival (OS) and AML evolution.

Long-term outcome of high risk patients with myelodysplastic syndromes or secondary acute myeloid leukemia receiving intensive chemotherapy.

Intensive chemotherapy (IC) used to be a common treatment approach for patients with higher-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia after MDS (sAML). We conducted a retrospective analysis of 299 patients, including a matched pair analysis comparing 96 patients receiving IC with 96 patients not undergoing IC, in order to evaluate the impact of IC on overall survival (OS) and to identify factors that influence remission rates and OS. Complete remission (CR) after first induction chemotherapy was reached in 50% of patients.

New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): Characteristics of refined MDS types.

Based on centrally diagnosed 3528 patients in the Düsseldorf registry, we validated the new proposals for the classification of the MDS by the WHO working group: 256 patients were diagnosed as MDSSLD (7,3%), 978 MDSMLD (27,7%), 227 MDS RS SLD (6,4%); 321 MDS RS MLD (9,1%), 159 MDS del(5q) (4,5%), 481 MDSEB 1 (13,6%), 620 MDSEB 2 (17,6%), and 148 MDS-U (4,2%). 352 patients (16,9% of the non blastic types) changed the category, mainly moving from RCMD to MDS RS MLD, RCUD and RCMD to MDS del(5q). Median survival times of the refined groups differed from more than 60 months in the MDSSLD (RS) groups, 37 months in the MDSMLD (RS) groups, 79 months of the MDS del(5q) group and 21 and 11 months in the MDSEB 1 and 2 groups, respectively.

Dynamic assessment of RBC-transfusion dependency improves the prognostic value of the revised-IPSS in MDS patients.

RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD.

Dysplastic erythroid precursors in the myelodysplastic syndromes and the acute myeloid leukemias: Is there biologic significance? (How should blasts be counted?).

The role of bone marrow dysplastic erythroid precursors (EP) in both MDS and AML has been the subject of considerable debate over the past several decades. We have analyzed a large series of adults with MDS and focused on whether any% of EP identified in the bone marrow aspirates of over 1400 patients selected from the Dusseldorf, Germany adult MDS Registry has prognostic relevance. The data was examined for varying% of blasts, the WHO prognostic MDS subtypes and the IPSS-R.

Causes of death in 2877 patients with myelodysplastic syndromes.

Patients with myelodysplastic syndromes face a poor prognosis. The exact causes of death have not been described properly in the past. We performed a retrospective analysis of causes of death using data of 3792 patients in the Düsseldorf registry who have been followed up for a median time of 21 months.

Response to erythropoietic-stimulating agents in patients with chronic myelomonocytic leukemia.

Background: The efficacy of erythropoietic-stimulating agents (ESA) in chronic myelomonocytic leukemia (CMML) is unknown. Our objective was to analyze erythroid response (ER) and overall survival (OS) in a series of 94 patients with CMML treated with ESA.

Methods: We analyzed a series of 94 patients with CMML treated with ESA included in the Spanish and Düsseldorf-MDS registries.

In patients with myelodysplastic syndromes with del(5q), factors other than age and sex contribute to the prognostic advantage, which diminishes over time.

This study aimed to determine the extent to which the prognostic advantage of myelodysplastic syndromes (MDS) with del(5q) is due to the more favourable age and sex distribution of patients in that group when compared to other MDS subtypes. A total of 1912 MDS patients from the Duesseldorf registry with less than 5% blasts in the bone marrow were evaluable and had complete covariates. As endpoints, overall survival and progression to acute myeloid leukaemia (AML) were considered.

Validation and proposals for a refinement of the WHO 2008 classification of myelodysplastic syndromes without excess of blasts.

In 2008, the WHO proposed changes in the classification of MDS regarding RCUD and MDS unclassifiable. We validated these proposals by using 2032 patients of the Düsseldorf MDS Registry. 10% of the patients had RCUD and 6% MDS-U.

Improved survival in MDS patients receiving iron chelation therapy - a matched pair analysis of 188 patients from the Düsseldorf MDS registry.

MDS patients are prone to develop transfusional iron overload. Iron overload may partly explain why transfusion dependency is associated with a decreased likelihood of survival. Our matched-pair analysis included 94 patients on long-term chelation therapy and 94 matched patients without it.

Evaluation of dysplasia through detailed cytomorphology in 3156 patients from the Düsseldorf Registry on myelodysplastic syndromes.

Using the Düsseldorf MDS registry with standardized cytomorphology we here describe dysplastic features in detail, concentrating on 16 different dysplastic features in the blood and 19 in the marrow in 3156 patients. The most frequent dysplastic features were megaloblastoid changes and bi- and multinuclearity in the erythropoiesis, pseudo-Pelger cells and hypogranulation in the granulopoiesis and micromegakaryoctes and mononuclear megakaryocytes in the megakaryopoiesis. The frequency of dysplastic changes did not differ significantly among the WHO types with the exception of MDS with del(5q) and CMML types.

Incidence and prevalence of myelodysplastic syndromes: data from the Düsseldorf MDS-registry.

Population-based data on patients with MDS are scarce. Here we report the incidence and prevalence of MDS based on data from the Düsseldorf MDS Registry. Cases in the city of Düsseldorf in the study period were identified from the MDS Registry.

Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome.

The incidence of myelodysplastic syndromes increases with age and a high prevalence of co-morbid conditions has been reported in these patients. So far, risk assessment in myelodysplastic syndromes has been mainly based on disease status. We studied the prognostic impact of comorbidity on the natural history of myelodysplastic syndrome with the aim of developing novel tools for risk assessment.

Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value.

Mutations in the TET2 gene are frequent in myeloid disease, although their biologic and prognostic significance remains unclear. We analyzed 355 patients with myelodysplastic syndromes using "next-generation" sequencing for TET2 aberrations, 91 of whom were also subjected to single-nucleotide polymorphism 6.0 array karyotyping.

Differences in the distribution of subtypes according to the WHO classification 2008 between Japanese and German patients with refractory anemia according to the FAB classification in myelodysplastic syndromes.

We reported the different clinical features between Japanese and German refractory anemia (RA) patients in FAB classification. We re-analyzed the clinical features by WHO classification revised in 2008. The frequencies of refractory cytopenia with unilineage dysplasia (RCUD) and myelodysplastic syndrome-unclassified (MDS-U) with pancytopenia in Japanese patients were higher than in German patients (p<0.

Platelet counts and haemorrhagic diathesis in patients with myelodysplastic syndromes.

Objectives: Most patients with myelodysplastic syndromes (MDS) present with single or multiple lineage cytopenias in peripheral blood despite a hypercellular bone marrow. Thrombocytopenia, attributable to ineffective platelet production by dysfunctional megakaryocytes, has been estimated to occur in 40-65% of patients. However, there are hardly any studies on the clinical relevance of low platelet counts in MDS.

Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome.

Purpose: Cryptic chromosomal aberrations, such as regions of uniparental disomy (UPD), have been shown to harbor homozygous mutations and are a common feature in myelodysplastic syndrome (MDS). We investigated the sequence integrity of 4q24 candidate tumor suppressor gene TET2 in MDS patients with UPD on chromosome 4.

Patients And Methods: The coding exons of TET2 were analyzed by 454 deep sequencing and Sanger sequencing in nine patients with UPD on 4q.