... responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations andfor expressing ... Diseases Fund Writing and editorial support were provided by Erin Nagle and Josh Collis and funded by Bristol-Myers Squibb Company 16 References 10 11 12 Sawyers CL: Chronicmyeloidleukemia N Engl ... MWN: Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure forchronicmyeloidleukemia Blood 2007, 110:2242-2249 Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J,...
... Page of and post two courses of chemotherapy (CT) for Ph-negative ALL, respectively and 72°C for min, and a final elongation at 72° C Then, the products were stored at 4°C Cytogenetic, FISH and RT-PCR ... BCR-ABL-negative acute myeloblastic leukemia masquerading as blast crisis after busulphan and interferon therapy for BCR-ABL-positive chronicmyeloidleukemiaLeukemia 1999, 13:126-129 Ohtsuka ... lymphocytic leukemia occurring after interferon and imatinib therapy for Ph-positive chronicmyeloidleukemia Journal of Hematology & Oncology 2010 3:14 Submit your next manuscript to BioMed Central and...
... Acute MyeloidLeukemia Incidence The incidence of acute myeloidleukemia (AML) is ~3.7 per 100,000 people per year, and the age-adjusted incidence is higher ... 4–6 years after exposure, and affected individuals have aberrations in chromosomes and Topoisomerase II inhibitor–associated leukemias occur 1–3 years after exposure, and affected individuals ... Chemical and Other Exposures Exposure to benzene, a solvent used in the chemical, plastic, rubber, and pharmaceutical industries, is associated with an increased incidence of AML Smoking and exposure...
... step and forces the clinician to correctly identify the entity and tailor treatment( s) accordingly Chromosomal Analyses Chromosomal analysis of the leukemic cell provides the most important pretreatment ... increased proliferation and antiapoptotic signals to the myeloid progenitor cell Presence of FLT3 ITD in patients with normal cytogenetics predicts for short remission duration and inferior survival ... nucleophosmin gene (NPM1) and C/EBP α that are associated with improved treatment outcome In contrast, overexpression of genes such as brain and acute leukemia, cytoplasmic (BAALC) predicts for poor outcome...
... leukemic blasts at diagnosis is characteristic of the monocytic subtypes and those with 11q23 chromosomal abnormalities Hematologic Findings Anemia is usually present at diagnosisand can be severe ... when they are, myeloid lineage is virtually certain (Fig 104-1) Poor neutrophil function may be noted by impaired phagocytosis and migration and morphologically by abnormal lobulation and deficient ... splenomegaly, hepatomegaly, lymphadenopathy, sternal tenderness, and evidence of infection and hemorrhage are often found at diagnosis Significant gastrointestinal bleeding, intrapulmonary hemorrhage,...
... hepatic, and renal systems Factors that have prognostic significance, either for achieving complete remission (CR) or for predicting the duration of CR, should also be assessed before initiating treatment ... all patients and cryopreserved for future use as new tests and therapeutics become available All patients should be evaluated for infection Table 104-2 Initial Diagnostic Evaluation and Management ... HSV-1, varicella zoster) RBC type and screen HLA typing of patient, siblings, and parents for potential allogeneic SCT Bone marrow aspirate and biopsy (morphology, cytogenetics, flow cytometry, molecular...
... emphasizes the importance of cytogenetic as well as the previously discussed molecular assessment of the leukemia cells at diagnosisand relevance of storing samples for potential later use A prolonged ... system bleeding and pulmonary leukostasis contribute to poor outcome with initial therapy In addition to pretreatment variables such as age, cytogenetics, and leukocyte count, several treatment factors ... more resistant disease Chronicand intercurrent diseases impair tolerance to rigorous therapy; acute medical problems at diagnosis reduce the likelihood of survival Performance status, independent...
... Figure 104-2 Flow chart for the therapy of newly diagnosed acute myeloidleukemiaFor all forms of AML except acute promyelocytic leukemia (APL), standard therapy includes a 7-day continuous ... continuous intravenous infusion for days Anthracycline therapy generally consists of daunorubicin intravenously on days 1, 2, and (the and regimen) Treatment with idarubicin for days in conjunction with ... synthesis and thereby overcome resistance to standard-dose cytarabine In two randomized studies, high-dose cytarabine with an anthracycline produced CR rates similar to those achieved with standard and...
... hospitalizations In most randomized studies, both G-CSF and GM-CSF have failed to improve the CR rate, disease-free survival, or overall survival Although receptors for both G-CSF and GM-CSF are present ... (CMV)-negative blood products should be used for CMVseronegative patients who are potential candidates for allogeneic SCT Leukodepleted products are also effective for these patients if CMV-negative products ... diagnosed AML have been stabilized They should be used thereafter for administration of intravenous medications and transfusions, as well as for blood drawing Antibiotic-impregnated catheters should...
... cytarabine is more effective than standard-dose cytarabine The Cancer andLeukemia Group B (CALGB), for example, compared the duration of CR in patients randomly assigned postremission to four ... days 1, 3, and 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 ... prolonged CR and increased the fraction cured in patients with favorable [t(8;21) and inv(16)] and normal cytogenetics, but it had no significant effect on patients with other abnormal karyotypes For...
... abelson murine leukemia virus) gene located on chromosome 9q34 Untreated, the disease is characterized by the inevitable transition from a chronic phase to an accelerated phase and on to blast ... cytotoxic drugs has been found, and no evidence suggests a viral etiology In the pre-imatinib era, cigarette smoking accelerated the progression to blast crisis and therefore adversely affected survival ... required for blastic transformation Finally, CML that develops resistance to imatinib is at an increased risk of progressing to accelerated/blast crisis Multiple pathways to disease transformation...
... molecular remission and cure A proposed imatinib treatment algorithm for the newly diagnosed CML patient is presented in Table 104-4 Table 104-4 Imatinib Treatment Milestones for Newly Diagnosed ... remissionb,d No cytogenetic remission Any cytogenetic remissionc 12 Minore or no cytogenetic Completeb,f partialc,g remission or cytogenetic remission 18 Partial, minor, or no cytogenetic remission ... Anytime Complete cytogenetic remissionb Loss of previously achieved hematologic, cytogenetic, or molecular remission a Nutritional Comprehensive Cancer Network, Chronic myelogenous leukemia b Denotes...
... transplantation For all other groups, patients receiving BMT from unrelated donors have higher rates of graft failure and acute andchronic GVHD and prolonged convalescence after treatment, compared ... in the chronic phase achieves 5-year disease-free survival in 40–70% of patients, with a 25% relapse rate BMT from an HLA-matched unrelated donor in chronic phase
... CML Specific milestones have been developed for chronicphase CML patients (Table 104-4) For example, chronic- phase CML patients who not achieve any cytogenetic remission following six months of ... the treatment algorithm of CML For example, patients who not achieve any cytogenetic remission at six months on imatinib will now be offered either dasatinib or SCT IFN-α, though FDAapproved for ... 98% The 5-year PFS for patients not achieving complete cytogenetic remission at 18 months was 87% These results have led to a consensus that molecular responses can be used as a treatment goal in...
... of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia Blood 105:3019, 2005 [PMID: 15604216] Tallman MS et al: Drug therapy for acute myeloidleukemia Blood ... approaches in chronicmyeloidleukemia J Clin Oncol 23:6316, 2005 [PMID: 16155014] Hughes TP et al: Monitoring CML patients responding to treatment with tyrosine kinase inhibitors Review and recommendations ... kinase inhibitors Review and recommendations for 'harmonizing' current methodology for detecting BCR-ABL transcripts and kinase domain mutations andfor expressing results Blood 108:28, 2006 [PMID:...
... Nilotinib for the frontline treatment of Ph(+) chronicmyeloidleukemia Blood 2009, 114:4933-4938 Saglio G, Baccarani M: First-line therapy forchronicmyeloid leukemia: new horizons and an update ... cells and BCR-ABL-induced chronicmyeloidleukemiaand acute lymphoblastic leukemia in mice Leukemia 2009, 23:1446-1454 Quintas-Cardama A, Cortes J: Omacetaxine mepesuccinate–a semisynthetic formulation ... with interferon and low-dose cytarabine for newly diagnosed chronic- phase chronicmyeloidleukemia N Engl J Med 2003, 348:994-1004 Masiello D, Gorospe G, Yang AS: The occurrence and management...
... (anti-sense) for b-actin The PCR conditions were as follows: for c-IAP-1 and XIAP, 94°C for min, 62°C for min, and 72°C for min; for Bcl-2, 94°C for 30 s, 62°C for 30 s, 72°C for 10 s; andfor b-actin: ... both dose- and time-dependent manners (Figure 2B, C, D) The IC 50 values at 24, 48, 72, and 96 h were 230.5, 86.9, 60.0, and 35.7 μM for KG1a, 68.5, 46.6, 28.8, and 23.5 μM for Kasumi-1, and 58.3, ... μg/ml, and 80 μM to 0.4 μg/ml, respectively) for 48 h, as shown in Figure 5A, B and Table S1 (Additional file 3) Both CalcuSyn software and Jin’s formula were used to determine synergy, and the...