Endogenous Retroviruses in Acute Myeloid Leukemia
LeukemiaMyeloidAllogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for numerous malignant hematologic diseases. Despite recent advances in the field, relapse rates are still high and the first cause of death. The identification of new relevant therapeutic targets is therefore urgently needed. Human endogenous retroviruses (HERVs) are accounting for 8% of the human genome. While silenced at the steady state (mainly by methylation mechanisms), HERVs reactivations have been described in different conditions such as auto-immune diseases or cancer, leading to an innate and adaptive immune response. Several questions are raised in the field of hematology where few data are available, and the exact role of HERVs in these diseases is still to define. Our team is currently working on the role of HERVs in different types of cancer. We developed a bioinformatics approach to identify overexpressed HERVs from RNAseq data. We also developed in vitro assays to assess the immunogenicity of different peptides from HERVs open reading frames and showed that several epitopes shared among different HERVs can induce a specific CD8+ T cell response. More recently, we have analyzed 151 acute myeloid leukemia (AML) RNAseq data from TCGA and identified multiple overexpressed HERVs in this disease. Immunogenicity test are currently ongoing with patient's blood at diagnosis. The main objective of this part of our project is to analyze the establishment of a HERVs-specific CD8+ T cell response participating in graft-versus-leukemia effect after HSCT for AML patients. Secondary objectives are to analyze relations between this response and different clinical factors such as the onset of GVHD or relapse. Peripheral blood mononuclear cells (PBMCs) from AML patients will be extracted and frozen at different time point: diagnosis, complete remission (pre-HSCT) and after HSCT (M3, M6 and M12). This prospective protocol is currently ongoing at the Centre Hospitalier Lyon Sud, with around 30 samples already available. After having selected relevant HERVs, specific dextramers identified by DNA barcode will be synthesized. These dextramers allowing the identification of specific T cell responses directed against up to 1000 epitopes, we will be able to screen specific T cells directed against HERVs overexpressed in AML for most common HLA. Dextramer staining will be performed on PBMCs after thawing. Positive cells will be sorted by flow cytometry and DNA will be expanded by PCR before performing sequencing, allowing the identification of specific sequences by its unique DNA barcode. The analyze of HERVs-specific CD8+ T cell responses after HSCT will allow us to better define HERVs role in the onset of graft-versus-leukemia effect. A specific T cell response without GvHD will define the relevance of such peptides as tumor specific antigens.
An Expanded Treatment Protocol (ETP) of Midostaurin (PKC412) in Patients 18 Years of Age or Older...
FLT3-mutated Acute Myeloid LeukemiaThe purpose of this study is to gather and evaluate additional safety data on the combination of midostaurin and standard of care for adult patients with newly diagnosed Fms-like tyrosine kinase receptor (FLT3) mutated Acute Myeloid Leukemia (AML) who are eligible for standard induction and consolidation chemotherapy and are without satisfactory treatment alternatives prior to the commercial availability* and reimbursement of midostaurin during the regulatory approval process
Treatment Patterns and Key Healthcare Resource Use in Acute Myeloid Leukemia (AML) With or Without...
Acute Myeloid Leukemia (AML)The purpose of this study is to retrospectively evaluate the treatment patterns and AML-related key healthcare resource use among AML patients, stratified by FLT3 mutation status, intensive chemotherapy (IC) eligibility, and relapsed or refractory (R/R) status.
Molecular Imaging to Capture Disease Heterogeneity in Acute Myeloid Leukemia
LeukemiaMyeloid1 moreThe current understanding of acute myeloid leukemia (AML) is that one site of bone marrow (BM) sampling serves as a window that represents all AML cells distributed throughout the BM, an assumption that has yet to be questioned. Simulation in mice led to inconsistent representation of the full BM, which can incorrectly suggest the absence of leukemic cells. Positron-emission tomography (PET) scan can detect areas of high metabolic activity in the body using for instance a radioactive sugar. In one report, its use in human AML has provided proof-of-principle evidence of unequal distribution of AML cells in BM. Accordingly, the alternative hypothesis is to test if PET scan can demonstrate if BM geography can alter AML cells spread and home them as distinct areas rather than uniform spread as if they are distributed in liquid state.
Italian Registry on the Prevalence of IDH1/IDH2 Mutations in Patients With Acute Myeloid Leukemia...
AMLAdultThis is a study where there are no interventions planned. Investigators will only collect data already in the patient's history and analyze it. Particularly, we are interested in molecular data from AML patients. This means that patients will follow their regular diagnostic and clinical practice. The analyses will be conducted according to the routine diagnostic and clinical practice as well and no additional blood withdrawal will be performed.
Ivosidenib Expanded Access Program in Relapsed/Refractory AML With an IDH1 Mutation
Acute Myeloid LeukemiaRelapsed Adult AML1 moreTo provide access to ivosidenib monotherapy to patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase 1 (IDH1) mutation.
Collect and Assess Tissue Samples From Subjects With Hematologic Malignancy
Acute Myelogenous LeukemiaMultiple Myeloma5 moreThis is a prospective, multicenter observational study to collect clinically annotated biospecimens in order to assess the correlation between ex vivo data generated by the Notable assay platform and clinical outcome.
Use of Saline-Washed Platelet and Red Cell Transfusions in Adult Acute Leukemia
LeukemiaMyeloid4 moreThe purpose of this study is to determine whether a novel standard of care protocol, washing red cell and platelet transfusions for younger patients with acute leukemia, has yielded improved clinical outcomes at Strong Memorial Hospital (Rochester, New York, USA). This standard of care was implemented based upon an earlier randomized trial (BMC Blood Disorders. 2004 Dec 10;4(1):6) The comparator will be historical controls from the medical literature.
High-dose Cytarabine and Survival in AML
Acute Myeloid LeukemiaIn adults with acute myeloid leukemia, especially those < 60 years of age, high-dose cytarabine consolidation therapy has been shown to influence survival, but the appropriate dose has not been defined.
Treatment of Acute Myeloblastic Leukemia in Younger Patients
Acute Myeloblastic Leukemiastudy of the value of the cytogenetics and the monitoring of the residual minimum disease in the standard treatment of acute myeloblastic leukemia.