Posted by rob on August 25, 2010 under Uncategorized | 
Plasma adiponectin levels are markedly elevated in imatinib-treated chronic myeloid leukemia (CML) patients: a mechanism for improved insulin sensitivity in type 2 diabetic CML patients?
J Clin Endocrinol Metab. 2010 Aug;95(8):3763-7
Authors: Fitter S, Vandyke K, Schultz CG, White D, Hughes TP, Zannettino AC
CONTEXT: The mechanism(s) by which imatinib improves glycemic control in chronic myeloid leukemia (CML) patients with type 2 diabetes remains unclear. OBJECTIVE: Adiponectin is an important regulator of insulin sensitivity that is secreted exclusively by adipocytes. We previously reported that imatinib promotes adipocytic differentiation of mesenchymal stromal cells. We therefore hypothesized that imatinib therapy would be associated with an increase in peripheral and intramedullary adiposity and elevated plasma adiponectin levels. RESEARCH DESIGN AND METHODS: Adiponectin levels in CML patient plasma, at diagnosis and then during imatinib mesylate therapy, was measured using an ELISA. Adiponectin multimers in plasma were analyzed using nondenaturing PAGE and immunoblotting. Intramedullary adiposity and adipose tissue mass was determined using histomorphometry and dual-energy X-ray absorptiometry, respectively. RESULTS: In CML patients, an increase in intramedullary and peripheral adiposity was observed after 6 months of imatinib therapy and plasma adiponectin levels, in the form of high- and low-molecular-weight complexes, were elevated 3-fold, compared with pretreatment levels, after 3, 6, and 12 months of therapy. CONCLUSIONS: Elevated adiponectin levels in imatinib-treated CML patients provide a possible mechanism for improved glucose and lipid metabolism reported for some imatinib-treated patients.
PMID: 20466781 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
A T315I mutation in e19a2 BCR/ABL1 chronic myeloid leukemia responding to dasatinib.
Leuk Res. 2010 Sep;34(9):e240-2
Authors: Cea M, Cirmena G, Garuti A, Rocco I, Palermo C, Cagnetta A, Moran E, Colombo N, Grasso R, Fugazza G, Gobbi M, Nencioni A, Ballestrero A, Patrone F
PMID: 20447687 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Treating imatinib resistance in the few in CML-A key step towards cure in all.
Leuk Res. 2010 Sep;34(9):1123-4
Authors: Giles FJ
PMID: 20417556 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Changes in the use of hematopoietic stem cell transplantation: a model for diffusion of medical technology.
Haematologica. 2010 Apr;95(4):637-43
Authors: Gratwohl A, Schwendener A, Baldomero H, Gratwohl M, Apperley J, Niederwieser D, Frauendorfer K
BACKGROUND: Innovations in hematology spread rapidly. Factors affecting the speed of introduction, international diffusion, and durability of use of innovations are, however, poorly understood. DESIGN AND METHODS: We used data on 251,106 hematopoietic stem cell transplants from 591 teams in 36 European countries to analyze the increase and decrease in such transplants for breast cancer and chronic myeloid leukemia and the replacement of bone marrow by peripheral blood as the source of stem cells as processes of diffusion. Regression analyses were used to measure the quantitative impact of defined macro- and microeconomic factors, to look for significant associations (t-test), and to describe the coefficient of determination or explanatory content (R(2)). RESULTS: Gross national income per capita, World Bank category, team density, team distribution, team size, team experience and, team innovator status were all significantly associated with some or all of the changes. The analyses revealed different patterns of associations and a wide range of explanatory content. Macro- and micro-economic factors were sufficient to explain the increase of allogeneic hematopoietic stem cell transplants in general (R(2) = 78.41%) and for chronic myeloid leukemia in particular (R(2) = 79.39%). They were insufficient to explain the changes in stem cell source (R(2) =26.79% autologous hematopoietic stem cell transplants; R(2) = 9.67% allogeneic hematopoietic stem cell transplants) or the decreases in hematopoietic stem cell transplants (R(2) =10.22% breast cancer; R(2)=33.17% chronic myeloid leukemia). CONCLUSIONS: The diffusion of hematopoietic stem cell transplants is more complex than previously thought. Availability of resources, evidence, external regulations and, expectations were identified as key determinants. These data might serve as a model for diffusion of medical technology in general.
PMID: 20378578 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
A comment on Megakaryocytic blast crisis as a presenting manifestation of chronic myeloid leukemia.
Leuk Res. 2010 Sep;34(9):1253
Authors: Lazarevic VLj
PMID: 20378169 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Testicular cancer developed in a chronic myeloid leukemia patient with a continued complete cytogenetic and molecular response to imatinib. A case report and review of the literature.
Leuk Res. 2010 Sep;34(9):e229-31
Authors: Kata D, Mrówka-Kata K, Seweryn M, Pajak J, Najda J, Kyrcz-KrzemieÅ? S
PMID: 20359744 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Safety profiles of second-line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia.
J Clin Nurs. 2010 May;19(9-10):1207-18
Authors: Tinsley SM
AIMS AND OBJECTIVES: To review the use of second-line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia (CML) and provide recommendations for managing adverse events (AEs) to maximise patient benefit. BACKGROUND: Treatment of CML has been revolutionised with the advent of tyrosine kinase inhibitors (TKIs) that target the breakpoint cluster region-Abelson (BCR-ABL) kinase. Imatinib is the only first-line TKI currently available for the treatment of CML; however, intolerance and resistance remain significant clinical challenges. The approved second-line treatment options for CML are dasatinib, nilotinib or escalated-dose imatinib. DESIGN: Review article. METHODS: Searches of PubMed, ASCO and ASH electronic databases for relevant search terms were performed between July 2008-January 2009. FINDINGS: Dasatinib has no cross-intolerance with imatinib, and the most frequent AEs (cytopenias and pleural and pericardial effusions) can generally be managed by dose interruption and reduction. Nilotinib has a high degree of haematologic cross-intolerance with first-line imatinib. As might be expected, high-dose imatinib has the potential for more severe AEs than standard-dose imatinib. CONCLUSIONS: There are known safety issues inherent to each TKI and close monitoring by nursing staff is necessary to identify and effectively manage AEs. RELEVANCE TO CLINICAL PRACTICE: All three TKIs have demonstrated potential for fluid retention and cardiotoxicity. Nurses should be aware of how these AEs manifest and intervene appropriately. The safety profiles of these TKIs clearly differs and it is important to consider factors such as comorbidities when making treatment decisions.
PMID: 20345830 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Emerging drugs for chronic myeloid leukemia.
Expert Opin Emerg Drugs. 2010 Jun;15(2):175-84
Authors: Cilloni D, Messa E, Rotolo A, Saglio G
IMPORTANCE OF THE FIELD: The deregulated tyrosine kinase activity of BCR-ABL has been demonstrated to be necessary and sufficient to maintain leukemia phenotype of chronic myeloid leukemia (CML) which, therefore, represents a unique model for the development of molecular targeted therapy and the first disease in which the tyrosine kinase inhibitors (TKIs) completely changed the therapeutical approach. The impressive results of TKIs in this model have been overshadowed by the development of clinical resistance. AREAS COVERED IN THIS REVIEW: This review focuses on clinical results with imatinib therapy and second generation TKIs. Furthermore, a summary of the guidelines for the management of TKI resistant patients is provided together with a description of the new drugs in clinical or preclinical phases which are developing to overcome resistance. WHAT THE READER WILL GAIN: Future perspective for the ‘cure’ of CML patients and new drugs designed for this purpose are suggested. TAKE HOME MESSAGE: CML therapy has dramatically changed in the last few years due to the introduction of targeted therapy. Studies on new drugs targeting different pathways other than BCR-ABL are ongoing to improve the clinical results.
PMID: 20201747 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Impact of additional chromosomal aberrations and BCR-ABL kinase domain mutations on the response to nilotinib in Philadelphia chromosome-positive chronic myeloid leukemia.
Haematologica. 2010 Apr;95(4):582-8
Authors: Kim TD, Türkmen S, Schwarz M, Koca G, Nogai H, Bommer C, Dörken B, Daniel P, le Coutre P
BACKGROUND: Additional chromosomal aberrations in Philadelphia chromosome-positive chronic myeloid leukemia are non-random and strongly associated with disease progression, but their prognostic impact and effect on treatment response is not clear. Point mutations in the BCR-ABL kinase domain are probably the most common mechanisms of imatinib resistance. DESIGN AND METHODS: We assessed the influence of additional chromosomal aberrations and BCR-ABL kinase domain mutations on the response to the second-generation tyrosine kinase inhibitor nilotinib after imatinib-failure. Standard cytogenetic analysis of metaphases was performed to detect additional chromosomal aberrations and the BCR-ABL kinase domain was sequenced to detect point mutations. RESULTS: Among 53 patients with a median follow-up of 16 months, of whom 38, 5 and 10 were in chronic phase, accelerated phase and blast crisis, respectively, 19 (36%) had additional chromosomal aberrations and 20 (38%) had BCR-ABL kinase domain mutations. The 2-year overall survival rate of all patients with-out additional chromosomal aberrations (89%) was higher than that of patients with such aberrations (54%) (P=0.0025). Among patients with chronic phase disease, overall survival at 2 years was 100% and 62% for patients without or with additional chromosomal aberrations, respectively (P=0.0024). BCR-ABL kinase domain mutations were associated with lower remission rates in response to nilotinib, with 9 of 20 (45%) of these patients achieving a major cytogenetic remission as compared to 26 of 33 (79%) patients without mutations (P<0.05). However, overall survival was not affected by BCR-ABL kinase domain mutations. CONCLUSIONS: Whereas BCR-ABL kinase domain mutations may confer more specific resistance to nilotinib, which will predominantly affect response rates, the presence of additional chromosomal aberrations may reflect genetic instability and, therefore, intrinsic aggressiveness of the disease which will be less amenable to subsequent alternative treatments and thus negatively affect overall survival. Conventional cytogenetic analyses remain mandatory during follow-up of patients with chronic myeloid leukemia under tyrosine kinase inhibitor therapy.
PMID: 20015884 [PubMed - indexed for MEDLINE]
More
