Posted by rob on July 28, 2009 under Uncategorized | 
Tyrosine kinase inhibitor-induced platelet dysfunction in patients with chronic myeloid leukemia.
Blood. 2009 Jul 9;114(2):261-3
Authors: Quintás-Cardama A, Han X, Kantarjian H, Cortes J
Dasatinib is associated with increased risk of bleeding among patients with chronic myeloid leukemia, even in the absence of thrombocytopenia, suggesting the presence of a hemostatic defect. We tested platelet aggregation in 91 patients with chronic myeloid leukemia in chronic phase either off-therapy (n = 4) or receiving dasatinib (n = 27), bosutinib (n = 32), imatinib (n = 19), or nilotinib (n = 9). All but 3 patients simultaneously receiving imatinib and warfarin had normal coagulation studies. All 4 patients off therapy had normal platelet aggregation. Impaired platelet aggregation on stimulation with arachidonic acid, epinephrine, or both was observed in 70%, 85%, and 59% of patients on dasatinib, respectively. Eighty-five percent of patients on bosutinib, 100% on nilotinib, and 33% on imatinib had normal platelet aggregation. Dasatinib 400 nM induced rapid and marked prolongation of closure time to collagen/epinephrine in normal whole blood on the PFA-100 system. In conclusion, dasatinib and, to some extent, imatinib produce abnormalities in platelet aggregometry testing.
PMID: 19414863 [PubMed - indexed for MEDLINE]
Posted by rob on under Uncategorized |
Imatinib: a designer drug, another cutaneous complication.
Clin Exp Dermatol. 2009 Jul;34(5):603-4
Authors: Dickens E, Lewis F, Bienz N
A 55-year-old man with a history of mild psoriasis was started on imatinib for chronic myeloid leukaemia. He developed new nail dystrophy after treatment with an exacerbation of his psoriasis. Although not a contraindication for this drug, it should be remembered that psoriasis may worsen with imatinib.
PMID: 19486036 [PubMed - indexed for MEDLINE]
Posted by rob on under Uncategorized |
JAK2 inhibitors: not the next imatinib but researchers see other possibilities.
J Natl Cancer Inst. 2009 Jul 15;101(14):980-2
Authors: Garber K
PMID: 19584324 [PubMed - indexed for MEDLINE]
Posted by rob on under Uncategorized |
Outpacing cancer.
Nat Med. 2009 Jul;15(7):718-22
Authors: Dorans K
PMID: 19584848 [PubMed - indexed for MEDLINE]
Posted by rob on under Uncategorized |
Molecular inversion probes reveal patterns of 9p21 deletion and copy number aberrations in childhood leukemia.
Cancer Genet Cytogenet. 2009 Aug;193(1):9-18
Authors: Schiffman JD, Wang Y, McPherson LA, Welch K, Zhang N, Davis R, Lacayo NJ, Dahl GV, Faham M, Ford JM, Ji HP
Childhood leukemia, which accounts for >30% of newly diagnosed childhood malignancies, is one of the leading causes of death for children with cancer. Genome-wide studies using microarray chips to identify copy number changes in human cancer are becoming more common. In this pilot study, 45 pediatric leukemia samples were analyzed for gene copy aberrations using novel molecular inversion probe (MIP) technology. Acute leukemia subtypes included precursor B-cell acute lymphoblastic leukemia (ALL) (n=23), precursor T-cell ALL (n=6), and acute myeloid leukemia (n=14). The MIP analysis identified 69 regions of recurring copy number changes, of which 41 have not been identified with other DNA microarray platforms. Copy number gains and losses were validated in 98% of clinical karyotypes and 100% of fluorescence in situ hybridization studies available. We report unique patterns of copy number loss in samples with 9p21.3 (CDKN2A) deletion in the precursor B-cell ALL patients, compared with the precursor T-cell ALL patients. MIPs represent an attractive technology for identifying novel copy number aberrations, validating previously reported copy number changes, and translating molecular findings into clinically relevant targets for further investigation.
PMID: 19602459 [PubMed - indexed for MEDLINE]
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Gender and ethnic differences in chronic myelogenous leukemia prognosis and treatment response: a single-institution retrospective study.
J Hematol Oncol. 2009 Jul 24;2(1):30
Authors: Lee JP, Birnstein E, Masiello D, Yang D, Yang AS
ABSTRACT: BACKGROUND: In the last decade the importance of ethnicity, socio-economic and gender differences in relation to disease incidence, diagnosis, and prognosis has been realized. Differences in these areas have become a major health policy focus in the United States. Our study was undertaken to examine the demographic and clinical features of chronic myelogenous leukemia (CML) patients presenting initially at the LAC+USC Medical Center, which serves an ethnically diverse population. RESULTS: Patients were evenly split by gender, overwhelmingly Hispanic (60.9%), and quite young (median age 39, range 17-65) compared with previously reported CML patient populations. Previous CML studies identified significant anemia (Hgb <12 g/dl), significant thrombocytosis (platelets >450 x 10;9/l), and significant leukocytosis (WBC >50 x 10;9/l) as significant adverse pretreatment prognostic factors. Using these indicators, in addition to the validated Hasford and Sokal scores, patients were stratified and analyzed via gender and ethnicity. A significantly greater proportion of women presented with significant anemia (p=0.019, Fisher’s exact test) and significant thrombocytosis (p=0.041, Fisher’s exact test) compared to men, although no differences were found in risk stratification or treatment response. MCV values for women were significantly (p=0.02, 2-sample t-test) lower than those for men, suggesting iron deficiency anemia. Focusing on ethnicity, Hispanics as a whole had significantly lower Hasford risk stratification (p=0.046, Fisher’s exact test), and significantly greater likelihood (p=0.016, Fisher’s exact test) of achieving 3-month complete haematological remission (CHR) compared with non-Hispanics at LAC+USC Medical Center, though differences in treatment outcome were no longer significant with analysis limited to patients treated with first-line imatinib. CONCLUSIONS: Female CML patients at LAC+USC Medical Center present with more significant adverse pre-treatment prognostic factors compared to men, but achieve comparable outcomes. Hispanic patients present with lower risk profile CML and achieve better treatment responses compared to non-Hispanic patients as a whole; these ethnic differences are no longer significant when statistical analysis is limited to patients given imatinib as first-line therapy. Our patients achieve response rates inferior to those of large-scale national studies. This constellation of findings has not been reported in previous studies, and is likely reflective of a unique patient population.
PMID: 19630970 [PubMed - as supplied by publisher]
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Authors: Vefring HK, Gruber FX, Wee L, Hovland R, Hjorth-Hansen H, Gedde Dahl T, Meyer P
The BCR-ABL fusion gene represents the hallmark of chronic myelogenous leukemia (CML) and is derived from a translocation between chromosome 9 and 22. The majority of CML patients have a breakpoint in the major BCR region of the BCR gene giving rise to e13a2 or e14a2 BCR-ABL transcripts. Occasionally, other BCR breakpoints occur. The current report describes two e6a2 CML patients with imatinib treatment failure and unusual disease progression. One patient was Philadelphia chromosome positive and one was Philadelphia chromosome negative with an atypical BCR-ABL rearrangement, ins (22;9).
PMID: 19641300 [PubMed - as supplied by publisher] (Source: Acta Haematologica)
Posted by rob on under Uncategorized |
Conclusion: These data quantify the deteriorating impact of CML disease progression and the impact of nonresponse to treatment. The study results add to evidence from other disease areas that systematic differences exist in preference values between countries. (Source: Value in Health)
