Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study).

Background: Intranasal (i.n.) drug application is a widely known and low-invasive route of administration that may be able to achieve rapid symptom control in terminally ill patients.

Multidrug-resistant organisms in allogeneic hematopoietic cell transplantation.

Objective: Multidrug-resistant organisms (MDRO) are a challenge in allogeneic hematopoietic cell transplantation (HCT). However, in the literature there is no comprehensive analysis on MDRO in HCT. In this retrospective, single-center analysis, we appraised prevalence and clinical impact of MDRO in 98 consecutive allogeneic HCT patients.

Cumulative radiation exposure from imaging procedures and associated lifetime cancer risk for patients with lymphoma.

The aim of this study was to systematically evaluate the cumulative radiation exposure and the associated lifetime-cancer-risk from diagnostic imaging in patients with Hodgkin-lymphoma-(HL) or diffuse-large-B-cell-lymphoma (DLBCL). 99 consecutive patients (53-males) diagnosed with HL or DLBCL were included in the study and followed. Based on the imaging reports, organ and effective-doses-(ED) were calculated individually for each patient and the excess lifetime risks were estimated.

Mammalian-target of rapamycin inhibition with temsirolimus in myelodysplastic syndromes (MDS) patients is associated with considerable toxicity: results of the temsirolimus pilot trial by the German MDS Study Group (D-MDS).

The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively.

Leukocyte DNA damage after reduced and conventional absorbed radiation doses using 3rd generation dual-source CT technology.

Purpose: Computed tomography (CT) scans are an important source of ionizing irradiation (IR) in medicine that can induce a variety of DNA damage in human tissues. With technological improvements CT scans at reduced absorbed doses became feasible presumably lowering genotoxic side effects.

Materials And Methods: For measuring DNA damage we performed γH2AX foci microscopy in peripheral blood mononuclear cells (PBMC) after exposure to reduced and conventional absorbed radiation doses using 3rd generation dual-source CT (DSCT) technology.

ERG induces a mesenchymal-like state associated with chemoresistance in leukemia cells.

Overexpression of the oncogene ERG (ETS-related gene) is an adverse prognostic factor in acute myeloid and T-cell lymphoblastic leukemia (AML and T-ALL). We hypothesize that ERG overexpression is associated with primary drug resistance thereby influencing the outcome in leukemia. We previously reported a cell-line based model of ERG overexpression which induced a potentially chemo-resistant spindle shape cell type.

Characteristics of MDS patients seen at private practices differ significantly from those treated at university hospitals in Germany.

Background: Myelodysplastic syndromes (MDS) are mainly a disease of the elderly. Commonly, MDS patients are treated in an outpatient setting making hematological/oncological private practices (PP) an important backbone in the management of MDS patients.

Methods: To gain more insights into the characteristics of patients with MDS treated in hematological/oncological PP and to evaluate the daily diagnostic routines and classification systems used, we performed questionnaire-based analyses.

The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation.

Background: The natural function of the C-C chemokine receptor type 5 (CCR5) is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32) located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation.

Clinical management of gastrointestinal disturbances in patients with myelodysplastic syndromes receiving iron chelation treatment with deferasirox.

Myelodysplastic syndromes are characterized by ineffective hematopoiesis resulting in peripheral cytopenias. The majority of patients is dependent on regular transfusions of packed red blood cells leading to a secondary iron overload which might result in organ damage. Therefore, sufficient iron chelation therapy in selected patients is mandatory.

Identification of defects in the transcriptional program during lineage-specific in vitro differentiation of CD34(+) cells selected from patients with both low- and high-risk myelodysplastic syndrome.

Objective: Development of myelodysplastic syndrome (MDS) is suggested to follow a multistep pathogenesis and is characterized by accumulation of molecular defects of the hematopoietic stem/progenitor cells, resulting in aberrant differentiation and proliferation.

Materials And Methods: To detect alterations within the transcriptional program in MDS-derived CD34(+) cells during lineage-specific differentiation, we performed serial gene expression analysis of in vitro differentiated erythro-, granulo-, and megakaryopoietic cells using oligonucleotide microarrays (HG-U133A, Affymetrix, Santa Clara, CA, USA). For selected genes, expression data were confirmed using real-time polymerase chain reaction.

Molecular mechanisms involved in the progression of myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis presenting with peripheral cytopenias in combination with a hyperplastic bone marrow. MDS patients have an increased risk of disease evolution to acute leukemia. Strong efforts have been made to gain further insights into the pathobiology of MDS.

Expression of interleukin 15 in primary adult acute lymphoblastic leukemia.

Background: Interleukin-15 (IL-15) has been associated with the growth, survival and biological behavior of leukemic cells and response to therapy. We determined the expression of IL-15 in lymphoblasts and evaluated its potential impact on the outcome in adult acute lymphoblastic leukemia (ALL).

Methods: Between June 1999 and June 2006, ALL samples were collected from 87 adult patients before initiation of antineoplastic therapy.

Expression of the adaptor protein Lnk in leukemia cells.

Objective: Tyrosine kinases are involved in cytokine signaling and are frequently aberrantly activated in hematological malignancies. Lnk, a negative regulator of cytokine signaling, plays critical nonredundant roles in hematopoiesis. By binding to phosphorylated tyrosine kinases, Lnk inhibits major cytokine receptor signaling, including c-KIT; erythropoietin receptor-Janus kinase 2 (JAK2); and MPL-JAK2.

Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation.

Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. We transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a patient with acute myeloid leukemia and HIV-1 infection.

High correlation of the proteome patterns in bone marrow and peripheral blood blast cells in patients with acute myeloid leukemia.

Background: When comparing myelogenous blasts from bone marrow and peripheral blood, immunophenotyping usually show a strong correlation of expression of surface antigens. However, it remains to be determined, whether this correlation also exists on the level of protein expression.

Method: Therefore, we investigated both bone marrow and peripheral blood blast cells from six patients with newly diagnosed acute myeloid leukemia (AML) using conventional two-dimensional electrophoresis in the first dimension and linear polyacrylamide gels (12%) in the second dimension.

Functional analysis of a novel DNA polymorphism of a tandem repeated sequence in the asparagine synthetase gene in acute lymphoblastic leukemia cells.

Asparagine synthetase (ASNS) is an enzyme expressed ubiquitously in mammalian cells. Here, we discovered two 14-bp tandem repeat (2R, wild-type) sequences in the first intron of the gene. The 14-bp sequence is similar to the three GC-boxes (GC-I, -II, and -III) found in the promoter region of the ASNS gene, as well as, the binding site of transcription factor Sp-1.

The hematology of anorexia nervosa.

Objective: Changes of the peripheral blood cell count in patients with anorexia nervosa (AN) are frequent. Anemia and leukopenia are observed in one-third of these patients. Examination of the bone marrow reveals in almost 50% of the patients with AN signs of bone marrow atrophy and can additionally suffer from a gelatinous bone marrow transformation.

Myelodysplastic syndromes: molecular pathogenesis and genomic changes.

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis presenting with peripheral cytopenias in combination with a hyperplastic bone marrow and an increased risk of evolution to acute myeloid leukemia. The classification systems such as the WHO classification mainly rely on morphological criteria and are supplemented by the International Prognostic Scoring System which takes cytogenetical changes into consideration when determining the prognosis of MDS but wide intra-subtype variations do exist. The pathomechanisms causing primary MDS require further work.

Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favorable outcome.

Purpose: Expression of the genes ERG (v-ets erythroblastosis virus E26 oncogene homolog) and BAALC (brain and acute leukemia, cytoplasmic) shows similarity during hematopoietic maturation and predicts outcome in acute myeloid leukemia. We hypothesized that like ERG, BAALC expression might be of prognostic significance in acute T-lymphoblastic leukemia (T-ALL) and that ERG and BAALC expression together would better identify the patient's risk profile.

Patients And Methods: ERG and BAALC mRNA expression were determined by real-time reverse transcriptase polymerase chain reaction in 153 adults with T-ALL.

RTP801 is a novel retinoic acid-responsive gene associated with myeloid differentiation.

Objective: Retinoids are crucial in the regulation of fundamental cellular processes including terminal differentiation of both normal and malignant myeloid progenitors. The aim of this study was to identify and characterize retinoic acid (RA) target genes.

Methods And Results: RTP801 is a recently cloned stress response gene that acts as a negative regulator of the mTOR pathway.