Active clinical trials for "Leukemia, Myelomonocytic, Juvenile"

This research study is studying identification of de novo Fanconi anemia in younger patients with newly diagnosed acute myeloid leukemia. Studying samples of tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to Fanconi anemia in patients with acute myeloid leukemia.

This study is collecting and storing malignant, borderline malignant neoplasms, and related biological samples from young patients with cancer. Collecting and storing samples of tumor tissue, blood, and bone marrow from patients with cancer to study in the laboratory may help the study of cancer in the future.

Hematopoietic stem cell transplantation (HSCT) is the only curative option for most of juvenile myelomonocytic leukemia (JMML). However, relapse after HSCT severely influence the long-term overall survival (OS). Researches demonstrate that these malignant myeloid disorders is a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents decitabine. However, hypomethylating therapy does not eradicate the malignant clone in JMML and an emerging concept with intriguing potential is the combination of hypomethylating therapy and HSCT. Graft-versus-host disease (GVHD) is major complication after HSCT as a threshold of the quality of patient life. Many data indicate that post -transplant cyclophosphamide (PT/Cy) is an effective method to control the occurrence of GVHD.

This registry is set up to collect real-world experience in the management of patients with myeloid neoplasms, in particularly in patients with MDS, CMML or AML, treated with hypomethylating agents in Austria and potentially other participating countries. This registry will collect data in a retrospective as well as in a prospective manner at various sites. The aim is to gain valuable insights on both efficacy and toxicity of these drugs in a routine clinical setting in patients with various comorbidities.

Chronic Myelomonocytic Leukemia (CMML) is the most frequent of myelodysplastic/myeloproliferative syndromes, as defined by the WHO classification of myeloid malignancies. The median age at diagnosis is around 70 years with a strong male predominance. CMML is a clonal disease of the bone marrow hematopoietic stem cell mainly characterized by persistent monocytosis (>1x109/L) and the presence of immature dysplastic granulocytes in the peripheral blood of CMML patients. Allogeneic stem cell transplantation (ASCT) remains the only curative option in CMML. However, CMML patients are rarely eligible for this kind of therapy, mainly due to their advanced age. The gold standard treatment of CMML thus remains hydroxyurea, which is usually initiated when the disease becomes proliferative, and demethylating agents, which could be efficient in the most aggressive forms of CMML. Nevertheless, the pathogenesis of CMML remains poorly understood and new therapies are urgently needed for patients in treatment failure. In recent years, a large numbers of gene mutations have been discovered in CMML, none of which are specific of this entity, as they can be encountered with different frequencies in other myeloid neoplasms. These mutated genes encode signaling molecules (NRAS, KRAS, CBL, JAK2, FLT3 and several members of the Notch pathway), epigenetic regulators (TET2, ASXL1, EZH2, IDH1, IDH2,.) and splicing factors (SF3B1, SRSF2, ZRSF2). Mutations in the transcription regulators RUNX1, NPM1 and TP53 have also been reported in CMML. However, the role of these mutations in leukemogenesis is still unclear. CMML is also characterized by defects in monocyte to macrophage differentiation. These defects in monocyte differentiation can be attributed to the presence of immature dysplastic granulocytes that secrete high levels of alpha-defensins HNP1-3 that antagonize the purinergic receptor P2RY6 in CMML patients. These CD14-/CD15+/CD24+ immature granulocytes that belong to the same clone than the leukemic monocytes seem to have immunosuppressive properties ressembling those of the myeloid-derived suppressor cells (MDCS) described in solid tumours. Whether these immature granulocytes contribute to autoimmune manifestations or immunoescape and progression of CMML is a conendrum and remains to be determined. In this context, the proposed project aims at identifying news insights into the pathophysiology of CMML through a better definition of the phenotype and function of monocytes and immature granulocytes that characterize this pathology.

To measure the rate of bone marrow release and the lifespan of classical monocytes in the peripheral blood of patients with a chronic myelomonocytic leukemia