Assessment Of Gh-Igf-1 Axis In Children With Chronic Myelogenous Leukemia (CML) In Remission
Chronic Myelogenous LeukemiaShort StatureCML is a myeloproliferative disorder defined by the presence of the Philadelphia chromosome, which arises from the reciprocal translocation of genes on chromosomes 9 and 22.It is rare in childhood and accounts for 2-3% of all leukemias in childhood. BCR-ABL gene on Philadelphia chromosome results in a 210kd fused BCR-ABL protein with constitutive tyrosine kinase activity, and subsequent activation of cytoplasmic and nuclear signal transduction pathways including STAT, RAS, JUN, MYC, and phosphatidylinositol-3 kinase. The ultimate result of such activation is the myeloid proliferation and differentiation and suppressed apoptosis. Children present with a higher WBC count, otherwise presentation is nearly identical to adults. Current treatment include tyrosine kinase inhibitors (TKI) and allogeneic stem cell transplant (SCT).Imatinibmesylate inhibits the tyrosine kinase (TK) activity of BCR-ABL1 and several related TKs, including c-kit and the platelet-derived growth factor receptor (PDGFR). Development of tyrosine kinase inhibitor (TKI) therapy has revolutionizedtreatment of CML. Imatinib or second generation TKIs (dasatinib or nilotinib) have become standard front-line therapy forchildren and adults with CML and are also important componentsof therapy for Ph+ acute lymphoblastic leukemia (ALL). TKIs are administered orally and cause a number of side effects including fatigue, hypertension, rash, impaired wound healing, myelosuppression, and diarrhea . The overall toxicity of TKIs, while less life-threatening than conventional cytotoxic chemotherapy, nevertheless is common, and may require dose reduction.Recently, proposed endocrine-related side effects of these agents include alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, glucose metabolism and adrenal function. Growth impairment is one of the major adverse effect of long-term imatinib treatment in children with CML. Multiple case reports have demonstrated growth retardation in children onimatinib.Imatinibmesylate inhibits the TK activity of BCR-ABL1 and several related TKs, including c-kit and theplatelet-derived growth factor receptor (PDGFR). It isthe inhibition of TK activity at the non-BCR-ABL sites that couldbe the likely cause for the adverse effect on growth. Severalstudies in adults have suggested that inhibition of c-kit,c-fms, and PDGF receptors results in modulation of bone metabolism. Other reports are focusing on disturbance of the growth hormone (GH) axis as a mechanism for growth impairment. Receptor and non receptor TK is expressed at multiple levels in GH-IGF-1 axis including GHRH-R, GH-R and IGF-1R. Inhibition of TKs with TKI, at any one of these level, might result in growth impairment. Various studies are available to show that Imainib therapy may cause short stature in children on prolonged treatment but exact mechanism by which this occurs is still not clear. Further, no treatment modality has been tried so far, for short stature in these children. So, the purpose of this study is to study GH-IGF1 axis in these children and to administer GH therapy to GH deficienct children in remission.
MRI Assessment of Leukemia Response to Therapy
Acute Myelogenous LeukemiaThe purpose of this study is to investigate if a type of magnetic resonance imaging (MRI) scan of the bone marrow before the start of standard chemotherapy can predict complete remission of leukemia patients after the therapy. This type of MRI scan, called dynamic contrast-enhanced MRI (DCE-MRI), measures bone marrow blood flow. For those patients who do not achieve complete remission status after initial therapy and will be treated with additional therapy, the investigators are also interested in determining if the second MRI exam before the additional therapy can predict complete remission. If successfully tested, the MRI exam may be used in the future to help with early identification of patients who are unlikely to respond to standard chemotherapy. This will allow for a personalized therapeutic plan to be developed for these patients at an early stage and prevent them from being exposed to toxic and ineffective therapies.
Follow-up of Ph+ Chronic Myleoid Leukemia Patients in Complete Cytogenetic Response With Interferon...
Chronic Myeloid LeukemiaObjectives This is an observational study aimed at updating the overall survival (OS), the progression free survival (PFS) to accelerated-blastic (AB) phase and the complete cytogenetic response (CCgR) duration of the CML patients who between 1986 and 2001 were treated with an IFN based therapy (either alone or in combination) and who obtained a CCgR. It also aims at analysing the clinical and biological features of this selected cohort of patients with persisting CCgR after treatment with IFN. Study design This study is an observational retrospective multicenter study. Assessment and Follow-up Patients' demographic data and retrospective collection of CML cytogenetic and molecular data will be reported in the "Assessment and Follow-up FORM". In this FORM the events related to therapy, disease and survival will also be reported. Duration of the study: The recruitment period is estimated in approximately 2 years.
Effect of 2nd Gen TKI in CML
Myeloid LeukemiaChronicStem cell transplantation will continue to be a treatment option for patients with chronic myeloid leukaemia, despite the introduction of tyrosine kinase inhibitors. However, many patients will have received prior therapy with TKIs, including Nilotinib or Dasatinib at the time of allogeneic stem cell transplantation. While the use of Imatinib prior to stem cell transplantation seems to have no adverse impact on the outcome of allogeneic stem cell transplantation little is known on the impact of prior use of second generation TK inhibitors. Therefore this non interventional prospective study addresses this question and patients undergoing allogeneic stem cell transplantation after prior use of 2nd generation TKIs will be followed by the data office office on engraftment, treatment related mortality, relapse rate and survival, prospectively. Details on TKI therapy will be collected by the participating centers, retrospectively. This is a non interventional prospective study. There is no upper limit to the number of patients entered, but it is estimated that up to 450 patients will be included in 150 centres for this non interventional prospective study. The registry will include patients for three years plus one more year for follow up and data analysis which should then be followed-up until the projected end of the non interventional prospective study.
Studying First Line Treatment of Chronic Myeloid Leukemia (CML) in a Real-world Setting
Chronic Myeloid LeukemiaThe purpose of this study is to better understand the use of tyrosine kinase inhibitors (TKI) in patients newly diagnosed with CML and their quality of life in a real-world setting.
Natural History Study of Patients With Chronic Myelogenous Leukemia
LeukemiaRATIONALE: Gathering information about patients with chronic myelogenous leukemia may help doctors learn more about the disease and find better methods of treatment and on-going care. PURPOSE: This natural history study is collecting health information and disease-related information over time from patients with newly diagnosed chronic myelogenous leukemia.
A Case-Cohort Study of Hematopoietic Malignancies and Related Disorders and Lung Cancer in Benzene-Exposed...
Lung CancerLymphoma3 moreThis study will examine the risks of workplace exposure to benzene, a substance known to lead to cancer of the blood and possibly of the lungs. It is used widely in industries and is a contaminant in the environment. Researchers from the National Cancer Institute and the China Center for Disease Control (formerly Chinese Academy of Preventive Medicine) had done previous studies of workers in manufacturing industries in China of people who worked at least 1 day from 1972 to 1987 in 12 cities in that country. Data were collected of approximately 75,000 workers exposed to benzene and 35,000 who were not, with the purpose of investigating the relationship between benzene exposure and cancer risk. For workers exposed to benzene, there was a significant risk of cancer affecting the blood cells and a 1.8-fold excess of lung cancer among them. This study will expand those findings and also identify the effects of benzene amounts and whether there is a genetic tendency for benzene poisoning. About 3,860 benzene-exposed workers from the 12 cities will be interviewed. Next-of-kin of deceased workers, and a subcohort (additional grouping) of participants will serve as a control group in the research. Patients who have worked at places where there was exposure to benzene will have a brief physical exam and samples of cells from a mouth rinse and samples from blood will be collected to study the genetic influence on developing blood diseases from workplace exposures. All participants or next-of-kin, for deceased, will be given a questionnaire about their work history, use of cigarettes and hair dyes, medications they take, and family history of cancer. Interviews of about 40 minutes long will be conducted at participants homes or workplaces, at a time convenient to them, and the interviews will be audiotaped.
Prospective Pilot Study of Bone Marrow and Peripheral Blood Samples From AML Patients to Characterize...
Acute Myeloid LeukemiaTreatment options and clinical outcomes for acute myeloid leukemia (AML) have not improved for more than 40 years. AML patients are still suffering from receiving costly, ineffective chemotherapy treatments with very high chances of bad side effects. The purpose of this study is to take a look at leukemia cells to see if the investigators can learn what makes them up and makes them aggressive and hard to treat. We want to use this information to create new treatments that the investigators hope are more effective and less harmful for AML patients. Newly diagnosed, relapsed or refractory (post induction therapy) AML patients that are 18 years of age or older will have bone marrow and blood samples taken for their regular AML treatment. When these tests are done during their treatment the investigators will need to get some extra blood and bone marrow to do this research. The patients will not be asked to have an extra needle stick or bone marrow biopsy to get these samples. The patients will have the same number of blood and bone marrow tests whether they participate in this study or not. We will only need to get about two teaspoons of blood and two teaspoons of bone marrow each time the patient has these tests during their regular AML treatment. The research the investigators do with these sample will not decide or change the care the patients get for their AML.
Investigating Intracellular and Plasma Imatinib Levels in Chronic Myeloid Leukemia
Chronic Myeloid LeukemiaThe purpose of this study is to find out if the level of imatinib in the bloodstream, and the level that leukemia cells will predict how quickly your chronic myeloid leukemia improves with the treatment. 1.1 Primary Objectives To determine if intracellular levels of Imatinib in leukemic blood cells within two weeks of treatment initiation of patients with chronic myeloid leukemia in chronic phase predicts molecular and cytogenetic response at 6 and 12 months post treatment 1.2. Secondary Objectives 1.2.1 To determine if hOCT-1 mRNA levels at diagnosis predict Imatinib intracellular levels within two weeks of treatment initiation. 1.2.2 To determine the correlation between intracellular Imatinib levels at two weeks of treatment initiation with plasma Imatinib levels at two and four weeks after treatment initiation. 1.2.3 To determine if plasma Imatinib levels four weeks after treatment initiation correlate with plasma Imatinib levels 12 months after treatment initiation. 1.2.4 To determine if intracellular levels of Imatinib in leukemic blood cells within two weeks of treatment initiation correlate with intracellular levels of Imatinib in normal leukocytes 12 months after treatment initiation.
Immune Checkpoint Receptors in AML-Leukemic Initiating Cells
Acute Myeloid LeukemiaThis project aim at deciphering immune mechanisms that allow the immunoescape of AML initiating cells.