Myelodysplastic syndrome and environment

In conclusion, our case highlights the unusual presentation of tropical pyomyositis in a temperate environment. It is important to consider this diagnosis in immunocompromised hosts, even in those with vague complaints such as muscle pain or erythema. The patient's immunocompromised state as well as the rarity of tropical pyomyositis outside of a tropical country led to a late diagnosis. Tropical pyomyositis is a potentially life threatening disease, but if recognized and treated early, the prognosis is good...

INTRODUCTION: The medical treatment of patients suffering from myelodysplastic syndromes has significantly changed during the last ten years, and this may have impacted the epidemiology of infectious complications. Some 'real world' experiences raised the issue of infections in this setting and the possible negative consequences for patients and health system: the higher the rate of hospitalizations and need for anti-infective therapies, the higher the treatment delays/withdrawal and consecutive the worse the outcome...

Genetic and epigenetic alterations contribute to the biological and clinical characteristics of myelodysplastic syndromes (MDS), but a role for socioeconomic environment remains unclear. Here, socioeconomic status (SES) for 283 MDS patients was estimated using the Scottish Index of Multiple Deprivation tool. Indices were assigned to quintile categorical indicators ranked from SES1 (lowest) to SES5 (highest). Clinicopathological features and outcomes between SES quintiles containing 15%, 20%, 19%, 30% and 16% of patients were compared...

Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia...

Myelodysplastic syndrome (MDS) is a clonal marrow stem cell disorder, characterized by ineffective haemopoiesis leading to blood cytopenias. As a disease of grey zone, along with the development of research, the exploration on its pathogenesis have been shifted from molecular genetics and the feature of immunophenotype to the epigenetic and micro environment. But at present, the pathogenesis of MDS is still not clear, the research of the molecular genetics and immunophenotype can not meet the needs of experimental and clinical application any longer...

The WHO classification provides the best diagnostic approach to myelodysplastic syndromes (MDS). However, biologic and analytic limitations have emerged in the criteria currently adopted to establish the diagnosis and to classify MDS. The provisional category of idiopathic cytopenia of undetermined significance (ICUS) has been proposed to describe patients in whom MDS is possible but not proven. To formulate a diagnosis of ICUS, a thorough diagnostic work-up is required and repeated tests should be performed to reach a conclusive diagnosis...

Brevundimonas diminuta are ubiquitous in the environment, but are infrequently isolated from clinical samples. Here we report a case of B. diminuta bacteremia in a man with myelodysplastic syndromes (MDS) at a teaching hospital in China and review the previously reported cases. The organism was confirmed by culture and 16s rRNA sequence analysis with highly sensitivity to broad-spectrum antibiotics. Our report and other cases demonstrated that the optimal therapeutic duration for B. diminuta infections in various situations remains to be established...

BACKGROUND: In patients with acquired aplastic anemia, destruction of hematopoietic cells by the immune system leads to pancytopenia. Patients have a response to immunosuppressive therapy, but myelodysplastic syndromes and acute myeloid leukemia develop in about 15% of the patients, usually many months to years after the diagnosis of aplastic anemia. METHODS: We performed next-generation sequencing and array-based karyotyping using 668 blood samples obtained from 439 patients with aplastic anemia...

OBJECTIVE: Immunocompromised patients now benefit from a longer life expectancy due to advanced medical techniques, but they are also weakened by aggressive treatment approaches and are at high risk for invasive fungal disease. We determined risk factors associated with an outbreak of invasive filamentous fungal infection (IFFI) among hospitalized hemato-oncological patients. METHODS: A retrospective, matched, case-control study was conducted between January 1, 2009, and April 31, 2011, including 29 cases (6 proven, 8 probable, and 15 possible) of IFFI and 102 matched control patients hospitalized during the same time period...

Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support...

OBJECTIVES: Posaconazole has shown superior clinical efficacy in the prevention of invasive fungal disease (IFD) among neutropenic patients as well as cost-effectiveness in the US healthcare setting vs fluconazole or itraconazole (FLU/ITRA) based on oral suspension formulations of each therapy. This study aims to provide an update on the cost-effectiveness of posaconazole in the current US healthcare setting to reflect bioequivalent tablet formulations of posaconazole and fluconazole, as well as changes in healthcare and drug costs...

To investigate whether the type of programmed cell death of myelodysplastic erythroid cells depends on their cellular context, we performed studies on cells from patients with low-risk myelodysplastic syndromes. We compared erythroid cells (and their precursor cells) from the mononuclear cell fraction with those from the hematon fraction, which are compacted complexes of hematopoietic cells surrounded by their own micro-environment. In directly fixed materials, erythroblasts exhibited signs of autophagy with limited apoptosis (<3%) based on ultrastructural characteristics and immunogold labeling for activated caspase-3...

The myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective haematopoiesis, bone marrow dysplasia and cytopenias. Failure of red cell production often results in transfusion dependency with subsequent iron loading requiring iron chelation in lower risk patients. Consistent with previous reports, we have observed haematopoietic improvement in a cohort of patients treated with the oral iron chelator deferasirox (DFX). It has been postulated that MDS patients have a pro-inflammatory bone marrow environment with increased numbers of activated T cells producing elevated levels of tumour necrosis factor (TNF), which is detrimental to normal haematopoiesis...

BACKGROUND: Mucormycosis is an invasive mycotic disease caused by fungi in the zygomycetes class. Although ubiquitous in the environment, zygomycetes are rarely known to cause invasive disease in immunocompromised hosts with a high mortality even under aggressive antifungal and surgical therapy. Clinically, mucormycosis frequently affects the sinus occasionally showing pulmonary or cerebral involvement. However skeletal manifestation with Rhizopus microsporus (RM) osteomyelitis leading to emergency surgical proximal femoral resection with fatal outcome has not been described yet...

In preventing invasive fungal disease (IFD) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), clinical trials demonstrated efficacy of posaconazole over fluconazole and itraconazole. However, effectiveness of posaconazole has not been investigated in the United States in real-world setting outside the environment of controlled clinical trial. We performed a single-center, retrospective cohort study of 130 evaluable patients ≥18 years of age admitted to Duke University Hospital between 2004 and 2010 who received either posaconazole or fluconazole as prophylaxis during first induction or first reinduction chemotherapy for AML or MDS...

Hematopoiesis in health and disease results from complex interactions between primitive hematopoietic stem cells (HSCs) and the extrinsic influences of other cells in the bone marrow (BM) niche. Advances in stem cell biology, molecular genetics, and computational biology reveal that the immortality, self-renewal, and maintenance of blood homeostasis generally attributed to individual HSCs are functions of the cells' behavior in the normal BM environment. Here we discuss how these advances, together with results of outcomes-based clinical epidemiology studies, provide new insight into the importance of epigenetic events in leukemogenesis...

Polyclonal mesenchymal cells (fibroblasts, endothelial cells, pericytes, osteoblasts, reticular cells, adipocytes, etc.) of the bone marrow create a functional microenvironment, which actively contributes to the maintenance of hemopoesis. This takes place through cellular interactions via growth factors, cytokines, adhesion molecules and extracellular matrix components, as well as through the control of calcium and oxygen concentration. Inflammatory and neoplastic diseases of the bone marrow result in pathologic interaction between hemopoietic progenitors and stromal cells...

Hematopoietic stem cells (HSCs) are a unique population of somatic stem cells that can both self-renew for long-term reconstitution of HSCs and differentiate into hematopoietic progenitor cells (HPCs), which in turn give rise, in a hierarchical manner, to the entire myeloid and lymphoid lineages. The differentiation and maturation of these lineages occurs in the bone marrow (BM) niche, a microenvironment that regulates self-renewal, survival, differentiation, and proliferation, with interactions among signaling pathways in the HSCs and the niche required to establish and maintain homeostasis...

The myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders of ineffective hematopoiesis that characteristically demonstrate peripheral blood cytopenia, bone marrow hypercellularity, and morphologically defined dysplasia of one or more hematopoietic lineages. Classical metaphase cytogenetics and judicious use of fluorescence in situ hybridization play central roles in the contemporary diagnosis and classification of MDS. An abundance of recent molecular studies are beginning to delineate additional genetic and epigenetic aberrations associated with these disorders...

An interstitial deletion of chromosome 5, del(5q), is the most common structural abnormality in primary myelodysplastic syndromes (MDS) and therapy-related myeloid neoplasms (t-MNs) after cytotoxic therapy. Loss of TP53 activity, through mutation or deletion, is highly associated with t-MNs with a del(5q). We previously demonstrated that haploinsufficiency of Egr1 and Apc, 2 genes lost in the 5q deletion, are key players in the progression of MDS with a del(5q). Using genetically engineered mice, we now show that reduction or loss of Tp53 expression, in combination with Egr1 haploinsufficiency, increased the rate of development of hematologic neoplasms and influenced the disease spectrum, but did not lead to overt myeloid leukemia, suggesting that altered function of additional gene(s) on 5q are likely required for myeloid leukemia development...