Active clinical trials for "Myelodysplastic Syndromes"

RATIONALE: Studying ways to diagnose fungal infections early may help doctors plan the best treatment. PURPOSE: This clinical trial is studying laboratory tests to see how well they find aspergillosis early in patients at high risk of fungal infection caused by treatment for hematologic cancer or other disease.

Primary Objective: 1. To assess the self-reported symptoms and the plasma cytokine levels of AML/MDS patients pretransplantation and posttransplantation with allogeneic blood and marrow in order to identify changes in symptoms (or symptom clusters) and changes in cytokines that may be related to the conditioning regimen and/or to the development of GVHD during the 100 days posttransplant. Based on the current literature, both animal and human research, in this study we hypothesize that increases in TNF alpha to be associated with poor appetite, sleep disturbance and fatigue, but not with increases in pain, depression and numbness.

Infections are a major life-threatening complication in patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML). Currently there is no guidelines about antibacterial prophylaxis to prevent infections in patients with myelodysplastic syndrome or acute myeloid leukaemia. The investigators will conduct a randomized prospective study to evaluate the benefit of prophylactic antibacterial by levofloxacin on febrile episode in Azacytidine treated patients (MDS and AML).

To investigate the efficacy of posaconazole as prophylaxis antifungal agent in aplastic anemia / hypoplastic myelodysplastic syndrome (AA/hMDS) patients undergoing antithymocyte globulin (ATG) treatment

Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal bone marrow neoplasms that predominate in the elderly, with a median age at diagnosis of 70 years. MDS are characterized by peripheral blood cytopenia and morphologic dysplasia for one or more hematopoietic cell lineage, reflecting ineffective hematopoiesis. The diagnostic work-up of MDS includes a bone marrow aspirate and biopsy, which is an invasive procedure, for cytomorphologic and cytogenetic evaluations. Because the prevalence of disease is lower than 20% in subjects referred for suspected MDS, many patients are exposed to unnecessary bone marrow aspiration-related discomfort and harms. An objective assay is highly desirable for accurately ruling out MDS based on peripheral blood samples, which may obviate the need for invasive bone marrow aspiration and biopsy in patients with negative results. Few studies have investigated the value of peripheral blood flow cytometric analysis for the diagnosis of MDS and/or chronic myelomonocytic leukemia (CMML). Although promising, these studies lacked replication of their results, used a case-control design, which was prone to spectrum bias, or yielded imprecise diagnostic accuracy estimates due to relatively limited sample sizes. Anecdotal evidence supports the potential of flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for the diagnosis of MDS and CMML. Myeloperoxidase is an enzyme synthetized during myeloid differentiation that constitutes the major component of neutrophil azurophilic granules. Myeloperoxidase expression may reflect neutrophil hypogranulation, which is a classical although subjective dysplastic feature of MDS. Flow cytometric analysis of myeloperoxidase expression in bone marrow neutrophil granulocytes has been used for discriminating low versus high grade MDS. Yet a study reporting on the accuracy of flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression for the diagnosis of MDS is still lacking, to our knowledge. In this study, the investigators hypothesize that flow cytometric analysis of neutrophil myeloperoxidase expression in peripheral blood may accurately rule out MDS and obviate the need for bone marrow aspiration and biopsy, with sensitivity approaching 100%, in routine practice. In this observational diagnostic accuracy study, burden will be null for recruited patients. No specific intervention is assigned to participants. All diagnostic testing, procedures, and medication ordering are performed at the discretion of attending physicians. Flow cytometry analysis of peripheral blood neutrophil myeloperoxidase expression will not require additional blood sample. A test result will have no impact on patient management. No follow-up visits are planned in this cross-sectional study.

Current diagnostic criteria for Immune ThrombocytoPenia (ITP) are mainly based on the presence of low numbers of platelets, excluding other multiple causes of thrombocytopenia, including immunodeficiencies, constitutional or acquired thrombocytopenia, hypersplenism and clonal hematological disorders such as MDS, disorders lymphoproliferative and acute myeloid leukemia (AML), among others. The analysis complementary tests for the diagnosis of ITP include studies basic systematic hematology, together with autoimmune assays and microbiological tests, while the evaluation of bone marrow is limited to elderly patients and/or patients resistant to treatment. Previous research has described the development of Myelodysplastic Syndrome (MDS) in patients with a previous diagnosis of ITP, and even the presence of MDS associated with genetic background. Therefore, it is conceivable fact that a percentage of cases with clinical signs of ITP in the moment of appearance may actually correspond to the first stages of MDS development in which bone marrow cells are not systematically evaluated in the initial presentation. The anomalous immunophenotypic patterns between multiple compartments of bone marrow cells and peripherally blood (PB) platelets have been characterized through flow cytometry. The flow cytometry currently represents an important complementary tool for diagnosis of MDS that has shown great effectiveness and applicability in the differential diagnosis of non-clonal cytopenias against early MDS and for the detection of stages prior to MDS. Besides, the flow cytometry has made it possible to detect the presence of coexisting features related to MDS in patients with other malignancies hematologic conditions such as multiple myeloma, AML, and lymphocytic leukemia chronic. Therefore, the immunophenotypic analysis of the cells of the bone marrow of patients with ITP at the time of appearance would help to identify the cases that underlie clonal hematopoiesis MDS type. In the present study it is planned a broad characterization immunophenotyping of multiple compartments of bone marrow cells and PB platelets from patients with recently diagnosed ITP and investigate their morphological antecedents, in order to identify those patients who show compatible clonal hematopoietic patterns with MDS evident (or at risk of development), as candidates to receive most appropriate therapeutic methods.

HSCT from an allogeneic donor is the standard therapy for high-risk hematopoietic malignancies and a wide range of severe non-malignant diseases of the blood and immune system. The possibility of performing HSCT was significantly limited by the availability of donors compatible with the MHC system. However, modern ex-vivo and in vivo technologies for depletion of T lymphocytes have made it possible to improve the outcomes of HSCT from partially compatible related (haploidentical) donors. In representative groups, it was shown that the success of HSCT from haploidentical donors is not inferior to standard procedures of HSCT from HLA-compatible unrelated donors. HSCT from haploidentical donors in children associated with the deficit of the adaptive immune response, which persists up to 6 months after HSCT and can be an increased risk of death of the patient from opportunistic infections. To solve this problem, the method of infusion of low doses of donor memory T lymphocytes was introduced. This technology is based on the possibility of adoptive transfer of memory immune response to key viral pathogens from donor to recipient. Such infusions have been shown to be safe and to accelerate the recovery of the pathogen-specific immune response. The expansion of virus-specific T lymphocytes in the recipient's body depends on exposure to the relevant antigen in vivo. Thus, in the absence of contact with the viral antigen, the adoptive transfer of memory T lymphocytes is not accompanied in vivo by the expansion of virus-specific lymphocytes and does not form a circulating pool of memory T lymphocytes, that can protect the patient from infections. Therefore the investigators assume that ex-vivo priming of donor memory lymphocytes with relevant antigens can provide optimal antigenic stimulation and may solve the problem of restoring immunological reactivity in the early stages after HSCT. Technically ex-vivo primed memory T lymphocytes will be generated by short incubation of CD45RA-depleted fraction of the graft (a product of T lymphocyte depletion) with a pool of GMP-quality peptides representing a number of key proteins of the viral pathogens. The following are proposed as targeted antigens: CMV pp65, EBV EBNA-1, EBV LMP12A, Adeno AdV5 Hexon, BKV LT, BKV VP1. An infusion of donor memory lymphocytes will be performed on the day +1 after transplantation. Parameters of the assessment will be safety and efficacy (immune response by day 60 and stability (responses by day 180).

Myelodysplastic syndromes (MDS) are a group of malignancies characterized by reduced differentiation and increased apoptosis of hematopoietic progenitor cells, leading to ineffective hematopoiesis. Treatment of MDS varies according to prognosis. Patients with low IPSS-R risk have a low probability of progression to acute myeloid leukemia (AML) and the treatment is aimed at controlling cytopenia and improving quality of life (QOL). Anemia is the most common disease feature, occurring in 80%-85% of low-risk patients, 40% of whom eventually become RBC transfusion-dependent (TD). Luspatercept is a recombinant fusion protein that selectively binds to ligands belonging to the transforming growth factor-beta (TGF-beta) superfamily. Luspatercept binds to GDF11, GDF8, activin B, and other ligands. This binding leads to inhibition of Smad2/3 signaling, which is abnormally high in disease models of ineffective erythropoiesis such as MDS, resulting in erythroid maturation and differentiation. Luspatercept is now approved for the treatment of adult patients with TD anemia due to very low-, low-, and intermediate-risk MDS with ring sideroblasts, who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy. FISiM (Fondazione Italiana Sindromi Mielodidplastiche) promotes a multicenter, retrospective observational study to collect information on the efficacy and safety of luspatercept in a real world Italian population of adult patients with transfusion-dependent anemia due to very low- and intermediate-risk MDS with ring sideroblasts

The study design is a prospective, non-interventional, observational single arm study. A minimum of 150 patients will be recruited from approximately 30 haematology/oncology sites in the Netherlands. In all cases, the decision to treat the patient with azacitidine was already made prior to the decision to enter the subject into the study. Recruitment will continue until end of June 2015, provided a minimum of 150 patients have been included in the study. When this date is reached, all patients on azacitidine will continue to be followed until the last patient enrolled has been followed for 12 months.

Myelodysplastic syndrome (MDS) is a group of medical conditions derived from progressive bone marrow failure that result in ineffective production of blood cells. Depending on the severity, MDS reduces the quality of life to the point of being life-threatening. There is a probability of death at all stages of the disease, due to complications and co-morbidities, with progression to acute myeloid leukemia (AML) being the worst evolution. Azacytidine is a nucleosidic analog with original epigenetic mechanism of action that is widely used for treating a variety of myelodysplasic syndromes. Although generally well tolerated, severe and sometimes life-threatening toxicities were unexpectedly observed in some patients. Genetic polymorphism affecting cytidine deaminase (CDA), the liver enzyme responsible for azacytidine detoxification step, could be responsible for poor clinical outcome due to on the one hand to severe toxicities in deficient patients, and on the other hand on treatment failure in ultrametabolizer patients.This clinical study aims at correlating the values in CDA levels with the risk of drug-related toxicities and to the clinical response to azacytidine treatment.