phase ii studies in chronic myeloid leukemia cml patients
Báo cáo y học: "A single-tube allele specific-polymerase chain reaction to detect T315I resistant mutation in chronic myeloid leukemia patients" pdf
... CL: Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia Cancer Cell ... different methods of detecting BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia on second-line dasatinib or nilotinib therapy after failure of imatinib Haematologica 2009, ... Beppu L, Gottardi E, et al: Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase J Clin Oncol 2009, 27:4204-4210 18 Shah NP, Nicoll...
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báo cáo khoa học: "P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia" pps
... Nilotinib is associated with minimal cross intolerance to imatinib in patients with imatinib-intolerant Philadelphia-positive (Ph+) chronic myelogenous leukemia (CML) in either chronic phase ... http://www.jhoonline.org/content/1/1/15 List of abbreviations CML: chronic myeloid leukemia; CP: chronic phase; AP: accelerated phase; BP: blast phase; TKI: tyrosine kinase inhibitor; IRIS: International ... of point mutations within the ABL kinase domain of BCRABL Such mutations inhibit the ability of imatinib to bind to BCR-ABL by corrupting the binding sites or preventing the kinase domain from...
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Báo cáo y học: " Failure of a non-authorized copy product to maintain response achieved with imatinib in a patient with chronic phase chronic myeloid leukemia: a case report" ppsx
... dose increase of imatinib mesylate in patients with chronic or accelerated phase chronic myelogenous leukemia with inadequate hematologic or cytogenetic response to initial treatment Clin Cancer ... [http://www.fda.gov/cder/regulatory/applications/ANDA.htm] Abbreviations BCR-ABL, breakpoint cluster region Abelson murine leukemia; CML, chronic myeloid leukemia; FDA, US Food and Drug Administration; CP, chronic phase; WBC, white blood cell count; ... accelerated phase or blast crisis phase of the disease The advent of therapies targeting tyrosine kinase resulted in a breakthrough in the management of CML For cost reasons, some third-party insurers...
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Báo cáo y học: "Dasatinib preferentially induces apoptosis by inhibiting Lyn kinase in nilotinib-resistant chronic myeloid leukemia cell line" pot
... Dasatinib preferentially induces apoptosis by inhibiting Lyn kinase in nilotinib-resistant chronic myeloid leukemia cell line Journal of Hematology & Oncology 2011 4:32 List of abbreviations CML: ... abbreviations CML: chronic myeloid leukemia; CP: chronic phase; ENESTnd: evaluating nilotinib efficacy and safety in clinical trials-newly diagnosed CML; FISH: fluorescence in situ hybridization; ... http://www.jhoonline.org/content/4/1/32 Page of Figure Cell growth inhibition by dasatinib and cellular signaling in a nilotinib resistant cell line (A) K562NR cells exposed to dasatinib or nilotinib for...
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báo cáo khoa học: "Two successful pregnancies in a woman with chronic myeloid leukemia exposed to nilotinib during the first trimester of her second pregnancy: case study" potx
... introduced in November 2007 for the treatment of patients with chronic or acute phase CML who were resistant to or intolerant of imatinib Evidence from an in- vitro study indicated that nilotinib ... potent than imatinib against cells expressing the wild-type bcr-abl [17] Compared to imatinib, nilotinib also has a higher binding affinity and selectivity for the inactive abl kinase conformation ... Cowan-Jacob SW, Lee FY, Heinrich MC, Deininger MW, et al.: In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants Cancer...
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báo cáo khoa học: "Evolution of T-cell clonality in a patient with Ph-negative acute lymphocytic leukemia occurring after interferon and imatinib therapy for Ph-positive chronic myeloid leukemia" pot
... of new clonal abnormalities following interferon-alpha induced complete cytogenetic response in patients with chronic myeloid leukemia: report of three cases Leukemia 1997, 11:767-771 26 Li YQ, ... in patients with CML [26], which indicate deficiency of cellular immunity in CML patients However, on the other hand, anti -CML cytotoxic T-cell clones were also identified in patients Wang et ... samples aspirated during different disease stage in a patient with CML CP -CML, the sample from chronic phase (October 2000); ALL, from the disease stage of acute lymphoblastic leukemia (October...
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báo cáo hóa học:" Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells" potx
... able to induce apoptosis in leukemia cells via caspase activation and involvement of both intrinsic and extrinsic pathways of apoptosis Background The Endocrine Disrupting Compounds are defined ... FLIP: FLICE Inhibitor Protein; TRAIL: TNF Related Apoptosis Inducing Ligand; RA: Retinoic Acid; RB: Retinoblastoma Competing interests The authors declare that they have no competing interests ... sub-G1 peack in all the cell lines tested, HL60 being the most resistant one In NB4 cells, a model from promyelocytic leukemia containing the fusion protein PMLRARα and sensitive to retinoids, the...
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Báo cáo hóa học: " Prognostic impact of ZAP-70 expression in chronic lymphocytic leukemia: mean fluorescence intensity T/B ratio versus percentage of positive cells" pot
... Becton-Dickinson, San Jose, CA) for 20 minutes, then treated with fixing and permeabilizing reagents (Fix&Perm kit, Caltag, Burlingame, CA) according to the manufacturer’s instructions, and finally stained ... following National Cancer Institute-Working Group guidelines [16] The concordance index (c index) was used to determine the predictive ability of ZAP-70 positivity in a TTT model Briefly, the c index ... expressing ZAP-70 according to T/B Ratiomethod (73), or expressing ZAP-70 according to either ISO- or Tmethods (30) Institution, in which ZAP-70 staining and analyses were performed utilizing a...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 1) ppsx
... Acute Myeloid Leukemia Incidence The incidence of acute myeloid leukemia (AML) is ~3.7 per 100,000 people per year, and the age-adjusted incidence is higher in men than in women (4.6 ... men than in women (4.6 versus 3.0) AML incidence increases with age; it is 1.9 in individuals 65 A significant increase in AML incidence has occurred over the past ... explosions in Japan had an increased incidence of myeloid leukemias that peaked 5–7 years after exposure Therapeutic radiation alone seems to add little risk of AML but can increase the risk in people...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 2) pot
... Myelomonocytic leukemia 20% M4Eo: Variant: Increase in abnormal marrow eosinophils M5: Monocytic leukemia 10% M6: Erythroleukemia (DiGuglielmo's disease) 4% M7: Megakaryoblastic leukemia 1% a ... Classificationc Incidence M0: Minimally differentiated leukemia 5% M1: Myeloblastic leukemia without maturation 20% M2: Myeloblastic leukemia with maturation 30% M3: Hypergranular promyelocytic leukemia ... myelomonocytic leukemia Acute monoblastic and monocytic leukemia Acute erythroid leukemia Acute megakaryoblastic leukemia Acute basophilic leukemia Acute panmyelosis with myelofibrosis Myeloid sarcoma...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 3) pps
... leukemogenesis; this information is increasingly being incorporated into the WHO classification For instance, the t(15;17) encodes a chimeric protein, promyelocytic leukemia (Pml)/retinoic acid receptor ... found in 5–10% of patients with normal cytogenetics and results in short remission duration FMS-like tyrosine kinase (Flt3) is a tyrosine kinase receptor important in the development of myeloid ... lymphoid lineages Activating mutations of the gene FLT3 are present in ~30% of adult AML patients due to internal tandem duplications (ITDs) in the juxtamembrane domain or mutations of the activating...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 4) pps
... diagnosis Significant gastrointestinal bleeding, intrapulmonary hemorrhage, or intracranial hemorrhage occur most often in APL Bleeding associated with coagulopathy may also occur in monocytic AML and ... leukocytosis or thrombocytopenia in other morphologic subtypes Retinal hemorrhages are detected in 15% of patients Infiltration of the gingivae, skin, soft tissues, or the meninges with leukemic blasts ... all in these patients This rare presentation is more common in patients with t(8;21) Physical Findings Fever, splenomegaly, hepatomegaly, lymphadenopathy, sternal tenderness, and evidence of infection...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 5) docx
... (leukemic infiltration, most common in monocytic leukemia) Skin infiltration or nodules (leukemia infiltration, most common in monocytic leukemia) Lymphadenopathy, splenomegaly, hepatomegaly Back pain, ... 104-2 Initial Diagnostic Evaluation and Management of Adult Patients with Acute Myeloid Leukemia History Increasing fatigue or decreased exercise tolerance (anemia) Excess bleeding or bleeding ... evaluation and initiation of appropriate therapy should follow (Table 104-2) In addition to clarifying the subtype of leukemia, initial studies should evaluate the overall functional integrity of...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 6) pps
... Advancing age is associated with a poorer prognosis, in part because of its influence on the patient's ability to survive induction therapy Age also influences outcome because AML in older patients ... status, independent of age, also influences ability to survive induction therapy and thus respond to treatment Chromosome findings at diagnosis are important independent prognostic factors Patients ... etiologic in renal tubular dysfunction, which could worsen other renal problems that arise during the initial phases of therapy Prognostic Factors Many factors influence the likelihood of entering...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 7) pot
... therapy) Patients with APL usually receive tretinoin together with anthracycline chemotherapy for remission induction and then consolidation chemotherapy (daunorubicin) followed by maintenance tretinoin, ... administered as a continuous intravenous infusion for days Anthracycline therapy generally consists of daunorubicin intravenously on days 1, 2, and (the and regimen) Treatment with idarubicin ... anthracycline in doses similar to those given initially, but for and days, respectively Our recommendation, however, is to change therapy in this setting Patients who fail to attain CR after two induction...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 8) pdf
... postremission regimens, patients with uncontrolled infections, or those participating in clinical trials Multilumen right atrial catheters should be inserted as soon as patients with newly diagnosed ... needed to maintain a platelet count >10,000–20,000/µL We believe that the platelet count should be kept at higher levels in febrile patients and during episodes of active bleeding or DIC Patients ... granulocytopenic patient after clinical evaluation, including a detailed physical examination with inspection of the indwelling catheter exit site and a perirectal examination, as well as procurement of cultures...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 9) pptx
... in up to 85% of patients refractory to tretinoin The use of arsenic trioxide is being explored as part of initial treatment in clinical trials of APL Additionally, studies combining arsenic trioxide ... 5), intermediate (400 mg/m2 for days by continuous infusion), or standard (100 mg/m2 per day for days by continuous infusion) doses of cytarabine A dose-response effect for cytarabine in patients ... Unlike patients with other types of AML, patients with this subtype benefit from maintenance therapy with either tretinoin or chemotherapy Arsenic trioxide produces meaningful responses in up...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 11) pps
... of a CML cell mass of 10,000/µL took 6.3 years No increase in CML incidence was found in the survivors of the Chernobyl accident, suggesting that only large doses of radiation can induce CML Pathophysiology ... exons Bcr/Abl fusion proteins, p210BCR/ABL, are produced that contain NH2terminal domains of Bcr and the COOH-terminal domains of Abl A rare breakpoint, occurring within the 3' region of the BCR ... hypomethylation of the LINE-1 retrotransposon promoter herald blastic transformation Further, interleukin 1β may be involved in the progression of CML to the blastic phase In addition, functional inactivation...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 12) docx
... alkaline phosphatase is low in CML cells Serum levels of vitamin B12 and vitamin B12–binding proteins are elevated Phagocytic functions are usually normal at diagnosis and remain normal during ... pulmonary insufficiency Patients with p230BCR/ABL-positive CML have a more indolent course Progression of CML is associated with worsening symptoms Unexplained fever, significant weight loss, increasing ... chronic phase Histamine production secondary to basophilia is increased in later stages, causing pruritus, diarrhea, and flushing At diagnosis, bone marrow cellularity is increased, with an increased...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 13) pptx
... Cancer Network, Chronic myelogenous leukemia b Denotes that at the indicated milestones, patients should stay on the same dose c Denotes that at the indicated milestones, for patients on 400 ... Table 104-4 Imatinib Treatment Milestones for Newly Diagnosed CML Patients Proposed Course of Actiona Transplantation from an HLAcompatible (related Continue sameb or unrelated) increase dosec ... cells containing the BCR/ABL transcript Hence the goal is complete molecular remission and cure A proposed imatinib treatment algorithm for the newly diagnosed CML patient is presented in Table...
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