Gamma Delta T Cells in AML
Acute Myeloid LeukemiaThe Royal Marsden NHS Foundation Trust is committed to improving patient experience; this research is being undertaken to try to develop a novel treatment for patients with Acute Myeloid Leukaemia (AML). Researchers aim to develop a new therapy which uses a patient's own immune cells called T cells to treat AML. In this study, numbers and properties of T cells which can be collected from the blood of patients with AML at various points throughout their treatment will be investigated. Blood samples will be collected at the same time as the patient's bone marrow test. If patients need further bone marrow tests during their course of treatment to assess the status of disease, the research team would ask that additional samples are taken at the same time as the bone marrow and blood will be collected at the same time as the routine blood draw. Following collection of blood samples, they will be used to purify a population of blood cells called Gamma Delta T cells which have been shown to have a potential role in control of cancers. In addition the researchers plan to determine whether it is possible to put a novel receptor called a chimeric antigen receptor (CAR) to potentially directly target leukaemia cells. Currently this is only an exploratory study and none of the samples collected will be used for treatment and is only to assess whether or not this strategy is feasible. This may however lead on to studies in the future looking at the safety and effectiveness of this strategy. This hopefully will lead in the future to improvements in treatment and outcome for patients with AML. If patients need further bone marrow tests during their course of treatment to assess the status of disease, the research team would ask that additional samples are taken at the same time as the bone marrow and blood will be collected at the same time as the routine blood draw. Following collection of blood samples, they will be used to purify a population of blood cells called Gamma Delta T cells which have been shown to have a potential role in control of cancers. In addition the researchers plan to determine whether it is possible to put a novel receptor called a chimeric antigen receptor (CAR) to potentially directly target leukaemia cells. Currently this is only an exploratory study and none of the samples collected will be used for treatment and is only to assess whether or not this strategy is feasible. This may however lead on to studies in the future looking at the safety and effectiveness of this strategy. This hopefully will lead in the future to improvements in treatment and outcome for patients with AML.
Decitabine for Chemotherapy Unfit Korean AML Patients in Real Practice
Acute Myeloid LeukemiaElderly1 moreProspective multicenter, open-lab el, observational, single arm study of decitabine. Subjects will be elderly patients with newly diagnosed, treatment-naïve AML who are unfit to receive and not candidate for intensive induction chemotherapy (iIC)
Samples From Leukemia Patients and Their Donors to Identify Specific Antigens
Acute Myeloid LeukemiaThe purpose of this project is to develop a process to identify highly personalized antigens that are uniquely expressed by the patient's own leukemia cells that can be used for cellular immune therapy.
Prevalence and Clinical Effect of IDH1/2 Mutations in Patients With Acute Myeloid Leukemia
Acute Myeloid LeukemiaIDH1 Gene Mutation1 moreAmong the most notable cancer genome-wide sequencing discoveries in recent years was the finding of mutation hot-spots in the isocitrate dehydrogenase (IDH) genes in grade II/III astrocytomas and oligodendrogliomas and in secondary glioblastomas. This was rapidly followed by identification of recurrent IDH1/2 mutations in myeloid neoplasms (MN), including acute myeloid leukemia (AML). Mutant IDH is now a therapeutic target of great interest in cancer research, especially in AML, given the limitations of current approved therapies and the encouraging early clinical data demonstrating proof of concept for investigational mutant IDH1/2 inhibitors. The origin of mutations in AML was explored by investigating the clonal evolution of genomes sequenced from patients with M1- or M3-AML and comparing them with hematopoietic stem/progenitor cells (HSPCs) from healthy volunteers. Six genes were found to have statistically higher mutation frequencies in M1 versus M3 genomes (NPM1, DNMT3A, IDH1, IDH2, TET2 and ASXL1), suggesting they are initiating rather than cooperating events. Prospective evaluation of serial 2- HG levels during treatment of newly diagnosed AML treated with standard chemotherapy revealed that both 2-HG level and mutated IDH allele burden decreased with response to treatment but began to rise again as therapy failed. The prognostic impact of IDH mutations in AML is under continued investigation and varies across studies. In this research project authors aim a) to define the prevalence and type of IDH1/2 mutations in AML patients; b) to define relationships between IDH1/2 mutations and other oncogenic mutations in AML, as well as to describe clonal evolution of the disease and c) to describe the clinical outcome of IDH1/2 mutated patients with AML treated with currently available treatments.
Oral Health Condition and Quality of Life in Children With Leukemia
LeukemiaLymphoblastic3 moreAmong the different types of cancer that most affect children, leukemia is the principal. One of the main treatments for leukemia is chemotherapy. Among the most common side effects of chemotherapy are nausea and/or vomiting, diarrhea, fatigue, alopecia, neuropathy, opportunistic infections, and oral mucositis. It is still necessary to establish which microorganisms are predominant in the oral microbiota of children with leukemia, which factors influence it, what is its relationship with oral mucositis and what is their impact in the quality of life. To better understand the risks of secondary infection, it is important to develop preventive and/or therapeutic strategies to control the side effects of antineoplastic treatment in the mouth that may negatively impact the quality of life, to expose the risk of death as well as raise hospital costs for the care of children with leukemia. Objective: To identify the clinical characteristics of the oral condition, types of microorganisms of the oral microbiota, and quality of life in children/adolescents with acute lymphoid leukemia and acute myeloid leukemia before and during antineoplastic treatment, and compare them with healthy children/adolescent individuals. Methodology: Longitudinal, case-control study, with a convenience sample. The study group, composed of children/adolescent individuals who have a definitive diagnosis of acute lymphoid leukemia or acute myeloid leukemia. The control group, non-syndromic children/adolescents, with no history of cancer, matched by age and gender. The clinical condition of the mouth will be evaluated by means of indexes: dental caries index (dmft index), gingival index (GA), and simplified oral hygiene index. The assessment of the quality of life through the ohip-14 and POS-version14 quality of life questionnaire and microbiological evaluation of saliva through MALDI-TOF analysis. Statistical analysis will be performed through relative risk for cohort study with more than three paired groups. Odds ratio, for the control group more than three controlled groups and Mcnemere, for comparison with the control group, for more than three paired groups.
Study the Novel Functions and Molecular Mechanisms of Vascular Endothelial Growth Factor-C (VEGF-C)...
Acute Myeloid LeukemiaVascular endothelial growth factor (VEGF)-C is recognized as a tumor lymphangiogenic factor based on the effects of activated VEGFR3 on lymphatic endothelial cells. VEGFR3 has been proposed as a specific marker for lymphatic endothelial cells. Recent studies indicated that VEGFR3 also expressed in a variety of human malignancies, including lung, colon rectal, or head and neck cancer. Moreover, VEGF-C/VEGFR3 axis was demonstrated in regulating angiogenesis, cell invasion, and metastasis in several solid tumors. The promotion of cell mobility in response to VEGF-C was required the involvement of adhesion molecule contactin-1. In addition to solid tumors, it has been reported that the VEGF-C/VEGFR3 axis is activated in subsets of leukemia patients. Until now, it has been demonstrated that higher endogenous VEGFC levels of acute myelogenous leukemia (AML) cells are related to decreased in vitro and in vivo responsiveness to chemotherapy; an effect that may result from inhibition of apoptosis by increasing Bcl-2/Bax ratios by the VEGF-C/VEGFR3 pathway. Thus, a functional VEGF-C/VEGFR3 system may exist in leukemia. However, the detail information concerning the role of VEGF-C/VEGFR3 in non-solid tumors is still lacking. Bone marrow neoangiogenesis plays a crucial pathogenic and possible prognostic role in AML. The VEGF-C/VEGFR3 axis has been proven in the regulation of solid tumors angiogenesis. In the investigators preliminary study, the investigators found VEGF-C may play a critical role in angiogenesis regulation of leukemic cells by upregulating cyclooxygenase-2 (COX-2). Furthermore, the investigators found that the upregulation of COX-2 also correlate with the VEGF-C-induced proliferation in leukemic cells and this phenomenon might further regulate the chemoresistance of VEGF-C. In this study, the investigators will investigate the extent of angiogenesis and chemoresistance induced by VEGF-C in leukemic cells. This study will provide evidences on the subject of the novel role of VEGF-C in leukemia. With progress in molecular biology of VEGF-C, its value as a therapeutic target is highly promising.
Medium Dose of Cytarabine and Mitoxantrone
Acute Myelogenous LeukemiaChemotherapyBy observation of the inpatients in shenzhen people's hospital,research the curative effect of the two chemotherapy schemes on AML-High dose of cytarabine and HAM.
Haploidentical Hematopoietic Stem Cell Transplantation for Acute Leukemias
LeukemiaMyeloid2 moreThis is a prospective observational cohort study of haploidentical transplantation with post-transplant cyclophosphamide for acute leukemias using reduced intensity conditioning for acute myeloid leukemia (AML) and myeloablative conditioning for acute lymphoblastic leukemia (ALL).
Changes in the Gut Microbiota of Patients Undergoing Allogeneic Stem Cell Transplantation (COLLECT)...
Acute Myeloid LeukemiaGraft-versus-host-disease2 moreCOLLECT is a monocentric, prospective, observational study, which aims to assess the association between changes in the intestinal microbiota and the incidence of gastrointestinal graft-versus-host diseases (GvHD). Patients admitted for performance of an allogeneic hematopoietic stem cell transplantation (HSCT) or patients with a first diagnosis of an acute myeloid leukemia (AML) will be enrolled and stool samples will be analyzed using next-generation sequencing. In addition to stool, blood and urine samples will be collected for cytokine and 3-indoxylsulfate analysis. Exposure to drugs will not be influenced and remains at the discretion of the treating physician.
Non-interventional, Long-term Follow-up of Subjects Who Completed ApoGraft-01 Study
Acute Myelogenous Leukemia (AML)Acute Lymphoblastic Leukemia (ALL)3 moreThis is a non-interventional, long-term follow-up study in subjects who received ApoGraft in study ApoGraft-01. Up to 12 subjects who completed ApoGraft-01 study will be offered to participate in this follow-up study. Subjects who completed ApoGraft-01 study and have signed informed consent for this follow-up study will be eligible to enroll. Subject will attend in-clinic visits up to 2 years post transplantation, and will undergo the following evaluations: acute and chronic graft versus host disease (GvHD) assessments, survival status (overall, relapse-free), disease status (disease relapse/recurrence), physical examination, safety laboratory and concomitant medication use.