Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation.

The combination of azacitidine and donor lymphocyte infusions (DLI) as first salvage therapy for relapse after allogeneic transplantation (allo-HSCT) was studied in 30 patients with acute myeloid leukemia (AML; n=28) or myelodysplastic syndromes (MDS; n=2) within a prospective single-arm multicenter phase-II trial. Treatment schedule contained up to eight cycles azacitidine (100 mg/m(2)/day, days 1-5, every 28 days) followed by DLI (from 1-5 × 10(6) to 1-5 × 10(8) CD3(+)cells/kg) after every second azacitidine cycle. A median of three courses azacitidine (range 1-8) were administered, and 22 patients (73%) received DLI.

Aberrant methylation of the M-type phospholipase A(2) receptor gene in leukemic cells.

Background: The M-type phospholipase A2 receptor (PLA2R1) plays a crucial role in several signaling pathways and may act as tumor-suppressor. This study examined the expression and methylation of the PLA2R1 gene in Jurkat and U937 leukemic cell lines and its methylation in patients with myelodysplastic syndrome (MDS) or acute leukemia.

Methods: Sites of methylation of the PLA2R1 locus were identified by sequencing bisulfite-modified DNA fragments.

Reconstitution of interleukin-17-producing T helper cells after allogeneic hematopoietic cell transplantation.

Interleukin 17A (IL-17)-producing CD4(+) T helper type 17 (Th17) cells have recently drawn attention as possible effector cells of acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) in murine models. Their role after allogeneic HCT in humans is unknown. In this prospective study, Th17, Th1/17, and Th1 cells were quantified in the peripheral blood of 80 patients within the first 3 months after allogeneic HCT using intracellular cytokine staining and flow cytometry.

Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndromes.

Despite new developments in innovative and potentially targeted drugs like hypomethylating agents (HMA), allogeneic hematopoietic stem cell transplantation (HCT) is still the only potentially curative treatment option for patients with myelodysplastic syndromes (MDS). Improvements in donor selection and supportive care, as well as the introduction of reduced-intensity conditioning, have improved the feasibility of this approach by reducing early mortality. As a result, the number of allogeneic HCTs performed in MDS patients mainly above the age of 60 years has significantly increased over the last decade.

Results from a 1-year, open-label, single arm, multi-center trial evaluating the efficacy and safety of oral Deferasirox in patients diagnosed with low and int-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent iron overload.

The majority of patients with myelodysplastic syndrome (MDS) present with anemia and will become dependent on regular transfusions of packed red blood cells (PRBC) with the risk of iron overload (IOL). Liver iron content best reflects the total body iron content, and measurement of liver iron concentration (LIC) by MRI is a validated tool for detection, but data in MDS is rather limited. Here we present the results of a multi-center trial evaluating the efficacy and safety of deferasirox (DFX) in low and intermediate-1 risk MDS patients with transfusion-dependent IOL.

MRI-based liver iron content predicts for nonrelapse mortality in MDS and AML patients undergoing allogeneic stem cell transplantation.

Purpose: Retrospective, surrogate marker-based studies have found inconsistent associations between systemic iron overload (SIO) and adverse outcome in patients undergoing allogeneic stem cell transplantation (allo-SCT). As a consequence, the impact of SIO in this context remains under debate. The aim of this study was to test whether the objective pretransplant quantification of liver-iron content (LIC) by magnetic resonance imaging (MRI) could circumvent these limitations and conclusively define the prognostic relevance of SIO.

Correlation of clinical response and response duration with miR-145 induction by lenalidomide in CD34(+) cells from patients with del(5q) myelodysplastic syndrome.

We examined whether lenalidomide exposure up-regulates miRNAs and mRNAs, previously shown to play a role in the disease phenotype of del(5q) myelodysplastic syndrome, in pre-treatment CD34(+) marrow cells. We hypothesized that increased expression would predict for clinical response. Changes in miR-143, miR-145, miR-146a, miR-146b, miR-378, miR-584, SPARC and RPS14 were examined in del(5q) (n=10) and non-del(5q) (n=18) myelodysplastic syndrome patient samples.

Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome.

Myelodysplastic syndromes and acute myeloid leukemia exemplify the complexity of treatment allocation in older patients as options range from best supportive care, non-intensive treatment (e.g. hypomethylating agents) to intensive chemotherapy/hematopoietic cell transplantation.

Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS.

Clonal cytogenetic abnormalities are a major risk factor for relapse after hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). We determined the impact of the recently established 5-group cytogenetic classification of MDS on outcome after HCT. Results were compared with the impact of the International Prognostic Scoring System (IPSS) 3 cytogenetic risk groups, and the additional effect of a monosomal karyotype was assessed.

Impact of lenalidomide on the functional properties of human mesenchymal stromal cells.

Objective: Lenalidomide (LEN) has emerged as a promising therapeutic option for the management of various hematologic malignancies. Although its direct mechanisms of action on malignant cells have been studied intensively, its effects on the stromal compartment of bone marrow have not yet been analyzed systematically. Therefore, we investigated whether LEN alters the functional capacity of mesenchymal stromal cells (MSCs) as the main cellular component of the bone marrow microenvironment.

Reconstitution of 6-sulfo LacNAc dendritic cells after allogeneic stem-cell transplantation.

Background: Infections and acute graft-versus-host disease (GvHD) represent major complications of allogeneic stem-cell transplantation (SCT). Dendritic cells (DCs) display an extraordinary capacity to induce innate and adaptive immune responses. Therefore, they play a crucial role in the elimination of pathogens and in the pathogenesis of acute GvHD.

Allogeneic hematopoietic cell transplantation in patients age 60-70 years with de novo high-risk myelodysplastic syndrome or secondary acute myelogenous leukemia: comparison with patients lacking donors who received azacitidine.

Standard first-line therapy for older patients with high-risk myelodysplastic syndrome (MDS) includes hypomethylating agents, such as azacitidine (AZA). However, the only approach with curative potential remains allogeneic hematopoietic cell transplantation (HCT). To date, no direct comparison of both strategies has been reported.

Clonal evolution including partial loss of human leukocyte antigen genes favoring extramedullary acute myeloid leukemia relapse after matched related allogeneic hematopoietic stem cell transplantation.

Background: Relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT) leaves few therapeutic options, and mechanisms of immune escape of recurring leukemic cells remain poorly understood. Recently, acquired loss of mismatched human leukocyte antigen (HLA) was demonstrated in patients with AML undergoing haploidentical allogeneic HSCT and was suggested not to occur in HLA-matched HSCT. We hypothesized that this mechanism applies to extramedullary AML relapse which occurs frequently after allogeneic HSCT and might also not be restricted to haploidentical HSCT.

The clinical, quality of life, and economic consequences of chronic anemia and transfusion support in patients with myelodysplastic syndromes.

Most patients with myelodysplastic syndromes (MDS) require transfusions due to chronic anemia. Apart from the acute risks associated with transfusions, chronic anemia and red blood cell (RBC) transfusion dependence impact negatively on survival and quality of life (QoL), and are associated with iron overload, potentially leading to organ damage. QoL studies demonstrate that regular transfusions do not correct the impact of chronic anemia.

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study.

Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months.

WNT5A is induced by inflammatory mediators in bone marrow stromal cells and regulates cytokine and chemokine production.

WNT5A has recently been implicated in inflammatory processes, but its role as a bone marrow stromal cell (BMSC)-derived mediator of joint inflammation in arthritis is unclear. Here, we investigated whether inflammatory stimuli induce WNT5A in BMSC to control inflammatory responses. WNT5A levels were determined in human BMSC after stimulation with lipopolysaccharide (LPS) or tumor necrosis factor α (TNF-α,) and in synovial cells and tissue of patients with rheumatoid arthritis (RA) and human TNF-α transgenic (hTNFtg) mice.

Update on developments in the diagnosis and prognostic evaluation of patients with myelodysplastic syndromes (MDS): consensus statements and report from an expert workshop.

Several new treatments for myelodysplastic syndromes (MDS) have recently become available, or are in development. Patients who could benefit from active treatment must be effectively identified and followed up. Therefore, guidelines for the diagnosis and prognostic evaluation of MDS need to be kept up to date with technological and scientific advances.