Study of the Outcome of Patients With Acute Myeloblastic Leukemia and Myelodysplastic Syndrome Receiving...
Myeloid LeukemiaMyelodysplastic SyndromesIron chelation, mostly associated with multiple red blood cell transfusion, is relatively common in patients with hematological malignancies receiving allo-HSCT. This multicenter prospective observational study is designed to establish the impact of iron chelation on relapse after allo-HSCT in patients with acute myeloid leukemia and myelodysplastic syndrome. The investigators will compare the results obtained in the prospective study to those observed in a historical retrospective cohort of paired patients who did not receive chelation. Given our clinical experience and literature results, the investigators will evaluate the Exjade chelator. Although not demonstrated, the presence of mutations of the HFE gene could play an indirect role on leukemogenesis by promoting overload. It is therefore important to evaluate the status in this patient population.
Minimal Residual Disease Evaluation on Cryopreserved Ovarian Fragments in Younger Patients Treated...
Acute Myeloid LeukemiaCryopreservation of ovarian cortex represents an option for fertility preservation in patients diagnosed with acute myeloid leukemia and requiring allogeneic stem cell transplantation. This pilot study aims to evaluate the minimal residual disease on ovarian fragments harvested before allogeneic stem cell transplantation at the time of complete remission.
Immunophenotyping and Xist Gene in AML
Acute Myeloid LeukemiaAcute myeloid leukemia (AML) is a heterogeneous disorder characterized by clonal expansion of myeloid progenitors (blasts) in the bone marrow and peripheral blood.Several studies have reported correlations of aberrantly expressed markers by flowcytometry with clinical outcome in AML. X-inactive specific transcript RNA was one of the first long noncoding RNAs (lncRNAs) to be discovered in the early 1990s. Xist RNA is the master regulator of XCI, the epigenetic process that equalizes the dosage of X-linked genes between female (XX) and male (XY) mammals. Yildirim et al., (2013) deleted Xist in the blood compartment of mice and demonstrated that mutant females developed a highly aggressive myeloproliferative neoplasm and myelodysplastic syndrome (mixed MPN/MDS) with 100% penetrance. Their study implies that human hematologic cancers may result from overdosage of X, either from Xist loss on Xi or from duplication of Xa. And they proposed that carcinogenesis is driven by a series of changes occurring in the HSC and further accumulated in mature hematopoietic cells. These changes are initiated by loss of Xist, which leads to progressive X reactivation, which in turn induces a cascade of unfavorable genome-wide changes that include dysregulation of genes involved in DNA replication, chromosome segregation, cell-cycle checkpoints, and hematopoiesis. A failure of HSC maturation and loss of long-term HSC in the marrow progressively shift hematopoiesis to extramedullary sites resulting in extra medullary hematopoiesis (EMH), thereby causally linking the X chromosome to cancer in mice. Thus, they concluded that Xist RNA not only is required to maintain XCI but also suppresses cancer in vivo. Indeed, the emerging role of aberrant gene dosage in diseases, whether of the X chromosome or for autosomes, brings with it the possible application of drugs that impact on epigenetic regulators in potential therapeutic strategies. To date, there are no published studies on human about Xist gene and its relationship with the immunophenotyping in AML patients. So, this will be the first study designed to explain its unexplored pathway in AML and detect its prognostic role and immunophenotypic association.
A Study for PRO of CML in Real Word
CML (Chronic Myelogenous Leukemia)Successful outcomes in CML require both prolonged adherence to oral TKI therapy by patients and careful monitoring of treatment responses by their physicians. Patient Reported Outcomes(PRO) assessment is important to facilitate decisions in the current treatment landscape of CML.
Long-term Outcomes for Acute Myeloid Leukemia Patients
Acute Myeloid LeukemiaThis international observational study aims at examining the patterns of health-related quality of life differences between long-term acute myeloid leukemia patients and their healthy peers from the general population.
Genome Wide SNP Array-based Approach to Detect Micro-cytogenetic Lesions and KIT Mutation to Improve...
Myeloid LeukemiaCore binding factor (CBF) positive acute myeloid leukemia (AML) consist of 15% of patients in overall AML, expected to harbor a favorable prognosis. However, around a half of cases relapses. Accordingly, more sophisticated classification in CBF positive AMLs is essential to achieve further improvement in the treatment outcome. The current study is designed to evaluate CBF positive AML patients with genome-wide SNP array and KIT mutation study in CBF positive AML patients diagnosed at the Samsung Medical Center and Hwasun Chonnam National University Hospital, Korea between 1994 and 2008. Construction of the CBF positive AML patient cohort: clinical database establishment (including treatment outcomes and prognosis) and extraction/storage of tumor cell DNAs from marrow samples, then processing of Affymetrix SNP array 6.0. Construction of prognostic predictive model using pharmacogenomics with the results of genotypes and copy number variations (CNVs). Detection of hidden microscopic cytogenetic lesions with SNP array technique, and correlation with clinical outcomes in CBF positive AML. Detection of KIT, FLT3/ITD, and NPM1 gene mutation and its correlation with clinical outcomes in CBF positive AML. The current study attempts to analyze genetic data of core binding factor (CBF) positive acute myeloid leukemia (AML) using genome wide SNP array technique with tumor DNAs collected at the time of diagnosis. To detect microcytogenetic lesions and will analyze its prognostic significance To analyze genome-wide genotypes and copy number variations (CNVs) using pharmacogenetic approach and will construct a prognostic predictive model To detect KIT, FLT3/ITD and NPM1 mutation and evaluate its prognostic significance. The present study will establish individualized therapy for CBF positive AML, will provide a basis for molecular marker guided clinical trial in CBF positive AML.
Bone Marrow Angiogenesis in Acute Myeloid Leukemia - Evaluated by Dynamic Contrast Enhanced Magnetic...
Acute Myeloid LeukemiaIn malignant or neoplastic disease, angiogenesis is defined as the generation of new capillaries from preexisting blood vessels, e.g. by sprouting or by intusseption. Through the pioneering work of Folkman, it was recognized that angiogenesis plays an important role in tumor development, progression, and metastasis. It is also conceivable that there are forms or developmental stages of leukemia, multiple myeloma, or lymphomas that will progress independently of angiogenesis. Synthesis of angiogenesis activators, such as vascular endothelial growth factor (VEGF) and other angiogenic factors, such as basic fibroblast growth factor (bFGF), has been demonstrated for leukemia cells, non-Hodgkin's lymphoma, and myeloma cells. Microvessel density is also significantly elevated over normal controls with progressive increases according to the stages of myelodysplastic syndrome. Increased microvessel density (MVD) in the bone marrow was found in patients with multiple myeloma in comparison to normal controls and increased MVD is an adverse prognostic marker in multiple myeloma. However, the functional status of the blood vessel (e.g. permeability) cannot be determined by the above mentioned methods.
Application of Nanopore Sequencing in Newly Diagnosed Acute Myeloid Leukemia Patients With Bloodstream...
Blood Stream InfectionGut Microbiota1 moreAcute myeloid leukemia (AML) patients are prone to blood stream infection (BSI) due to bone marrow suppression, oral and gastrointestinal mucositis, endovascular tubes, and the application of a large number of broad-spectrum antibiotics. The associated mortality rate is as high as 7.1 %-42%. The use of antibiotics within one hour after the first observation of hypotensive symptoms can guarantee a 79.9% survival rate. For every hour of delay, the patient's survival rate will drop by 7.6%. At present, the blood culture test cycle is long and the positive rate is low. Other infection-related indicators (PCT, CRP) or next-generation sequencing are not highly specific and easy to be misdiagnosed. X-ray, CT and other examinations only have a certain auxiliary value for the infected site. We need new diagnostic tools to accurately identify pathogens. Nano-seq is a next-generation sequencing technology for single-molecule, real-time sequencing and analysis. With ultra-long sequencing read length, it can quickly and accurately identify BSI pathogens types, and give appropriate drug sensitivity results based on drug resistance genes to meet the needs of 99.9% pathogen screening. At the same time, we hope to conduct a prospective evaluation to target high-risk groups of AML prone to BSI in the early stage. The intestine is the body's largest immune organ and the largest reservoir of microbial pathogens. The expansion of certain gut microbiota usually precedes BSI. If there is a correlation between the gut microbiota and MDR-BSI, the colonization and changes of the intestinal flora can be used to predict the risk of BSI in patients during treatment, and preventive measures such as early decolonization or biological intervention will reduce the risk of infection in the future. Combined with Nano-seq and various existing clinical pathogen detection technologies to reduce the occurrence and progress of clinical BSI.
Conventional and Experimental Chemotherapy With Allogeneic Transplant in Young Patients With Acute...
Acute Myeloid LeukemiaThe purpose of this study is evaluate patients with acute myeloid leukemia (<=66 years), treated with conventional and experimental chemotherapy following allogeneic transplantation. THis patients have been enrolled from 2000 to 2011 at the Division of Hematology, Molinette University Hospital. The purpose of data collection is to assess, with retrospective analysis, the clinical outcome divided by risk class and evaluated in patients who achieve complete remission after induction therapy and consolidation.
Genetic Predictive Model Based on Single Nucleotide Polymorphisms in the DNA Repair Pathway and...
Patients With Acute Myeloid LeukemiaPatients Receiving Induction/Consolidation ChemotherapyThe main component in the treatment of acute myeloid leukemia (AML) is consist of anthracycline (such as daunorubicin or idarubicin) and cytarabine. Inter-individual variability of transport/metabolism of the chemotherapeutic agent and several genetic pathways involved in the drug action might be associated with different response following the treatment for AML usually consisted of chemotherapy and/or transplantation. One of potential pathways involved in the drug action is DNA repair pathway, accordingly single nucleotide polymorphisms (SNPs) in the DNA repair machinery pathway might be a predictive marker for therapy outcomes in AML. Several genes were involved in the DNA repair machinery which are 1) Nonhomologous end joining (NHEJ) pathway involved in the G1/S phase, 2) Homologous recombinational repair (HRR) pathway involved in the S/G2 phase. XRCC4, LIG4, MRN and ATM are well known genes involved in the NHEJ pathway, while MRE11, RAD50, NBS1 (MRN), RAD51, XRCC2, XRCC3, RAD51B, RAD51C, RAD 51D, RAD52 or RAD54 are known to be associated with HRR pathway. A study suggested that the SNPs in the DNA repair pathway was involved in the susceptibility of secondary AML developing after chemotherapy or autologous hematopoietic stem cell transplantation, thus these SNP markers could become a predictive marker for secondary AML. However, it has never been investigated for multiple candidate pathways simultaneously with relateively larger number of patients. Accordingly, the current study attempts to investigate the potential role of the genotype markers in multiple candidate pathways, esp. focused on the DNA repair machinery, with respect to response following chemotherapy or survival of AML patients. Total of over 500 archived samples from the patients diagnosed as acute myeloid leukemia at the Samsung Medical Center, Seoul, Korea will be included, and genomic DNAs will be extracted and will be examined for their genotypes of the candidate SNPs involved in the DNA repair pathways. Then statistical analysis will be pursued for single marker analysis, haplotype analysis and for the construction of genetic risk model based on the multivariate analysis.