Posted by rob on November 17, 2010 under Uncategorized | 
Nonspecific Capillary Proliferation and Vasculopathy Indicate Skin Hypoxia in Erythromelalgia.
Arch Dermatol. 2010 Nov 15;
Authors: Kalgaard OM, Clausen OP, Mellbye OJ, Hovig T, Kvernebo K
OBJECTIVE: To report on the histopathologic findings of affected skin in consecutively collected biopsy specimens from 49 patients with erythromelalgia (EM). DESIGN: Skin biopsy specimens were obtained from the foot arch and analyzed by light microscopy, immunofluorescence microscopy, and electron microscopy. SETTING: Oslo University Hospital-Gaustad, University of Oslo, Oslo, Norway. PARTICIPANTS: Thirty-one patients had primary EM, 17 patients had secondary EM, and 1 patient had erythromelalgic syndrome. Main Outcome Measure Evidence of microvascular abnormalities in skin biopsy specimens. RESULTS: Light microscopy showed evidence of capillary proliferation in 10 of 31 patients with primary EM and in 1 of 17 patients with secondary EM. The biopsy specimen from the patient with erythromelalgic syndrome showed numerous capillary nests with endothelial cell defects and a slight perivascular inflammatory reaction. Among the 17 secondary EM cases, sparse perivascular lymphocyte infiltrations were observed in the biopsy specimens from 2 patients with chronic myelogenous leukemia and 1 patient with diabetes mellitus. Eleven patients also had signs of vasculopathy based on findings of immunodeposits of C3 and fibrin. Six of 30 patients with primary EM showed endothelial abnormalities on electron microscopy. All 3 investigations showed unremarkable biopsy results in 16 cases. CONCLUSIONS: Histopathologic analysis is not useful as a routine diagnostic tool in EM because no morphological changes are specific to EM. The capillary proliferation and vasculopathy are assumed to be a consequence of intermittent skin hypoxia (vascular hypothesis of pathogenesis). Whether the proliferation is a consequence of EM or a pathogenic factor in the development of the disease is uncertain.
PMID: 21079053 [PubMed - as supplied by publisher]
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Correlations between imatinib pharmacokinetics, pharmacodynamics, adherence, and clinical response in advanced metastatic gastrointestinal stromal tumor (GIST): An emerging role for drug blood level testing?
Cancer Treat Rev. 2010 Nov 13;
Authors: von Mehren M, Widmer N
Imatinib is the standard of care for patients with advanced metastatic gastrointestinal stromal tumors (GIST), and is also approved for adjuvant treatment in patients at substantial risk of relapse. Studies have shown that maximizing benefit from imatinib depends on long-term administration at recommended doses. Pharmacokinetic (PK) and pharmacodynamic factors, adherence, and drug-drug interactions can affect exposure to imatinib and impact clinical outcomes. This article reviews the relevance of these factors to imatinib’s clinical activity and response in the context of what has been demonstrated in chronic myelogenous leukemia (CML), and in light of new data correlating imatinib exposure to response in patients with GIST. Because of the wide inter-patient variability in drug exposure with imatinib in both CML and GIST, blood level testing (BLT) may play a role in investigating instances of suboptimal response, unusually severe toxicities, drug-drug interactions, and suspected non-adherence. Published clinical data in CML and in GIST were considered, including data from a PK substudy of the B2222 trial correlating imatinib blood levels with clinical responses in patients with GIST. Imatinib trough plasma levels <1100ng/mL were associated with lower rates of objective response and faster development of progressive disease in patients with GIST. These findings have been supported by other analyses correlating free imatinib (unbound) levels with response. These results suggest a future application for imatinib BLT in predicting and optimizing therapeutic response. Nevertheless, early estimates of threshold imatinib blood levels must be confirmed prospectively in future studies and elaborated for different patient subgroups.
PMID: 21078547 [PubMed - as supplied by publisher]
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Palatal mucormycosis in patients with hematologic malignancy and stem cell transplantation.
Med Mycol. 2010 Nov 15;
Authors: Akhrass FA, Debiane L, Abdallah L, Best L, Mulanovich V, Rolston K, Kontoyiannis DP
We present two patients with acute myelogenous leukemia who developed palatal mucormycosis, as well as a review of 15 well described reported cases of the same condition in patients who had hematologic malignancy and had undergone hematopoietic stem cell transplantation. Early diagnosis of palatal mucormycosis requires high suspicion of the disease along with a thorough oral examination. Mucormycosis is a devastating disease with a high mortality rate, thereby stressing the importance for early appropriate antifungal therapy in immunocompromised patients with palatal lesions while awaiting the results of histopathology and cultures.
PMID: 21077735 [PubMed - as supplied by publisher]
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Are chronic myeloid leukemia patients more at risk for second malignancies? A population-based study.
Am J Epidemiol. 2010 Nov 1;172(9):1028-33
Authors: Rebora P, Czene K, Antolini L, Passerini CG, Reilly M, Valsecchi MG
The authors used cancer registry data to assess the incidence rate of second primary cancers among chronic myeloid leukemia (CML) patients and the long-term survival of CML patients before the introduction of tyrosine kinase inhibitors. In the Swedish Cancer Registry, the authors identified 2,753 adult CML patients diagnosed between 1970 and 1995 who were followed through December 2007. Standardized incidence ratios (SIRs) and relative survival ratios were computed. With a total of 145 subsequent primary malignancies, an increased incidence rate of second malignancy was found for stomach cancer (SIR = 2.76, 95% confidence interval (CI): 1.33, 5.08), skin cancer (SIR = 5.36, 95% CI: 3.18, 8.47), urogenital tract cancer (SIR = 1.61, 95% CI: 1.15, 2.21), and lymphoid leukemia (SIR = 5.53, 95% CI: 1.79, 12.89). Long-term relative survival figures showed that CML was related, in the era prior to the introduction of imatinib, to a very steep decline in survival (2 years from diagnosis, relative survival = 51%, 95% CI: 49, 53). This was in spite of a marginal improvement after 1985, possibly related to the introduction of interferon-? for treatment. These estimates constitute a relevant reference for future studies and a benchmark for comparisons with prognosis in CML patients after chronic use of tyrosine kinase inhibitors.
PMID: 20861143 [PubMed - indexed for MEDLINE]
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Optimizing outcomes in patients with chronic myeloid leukemia in chronic phase: comparative safety profiles of newer agents.
Leuk Lymphoma. 2010 Aug;51(8):1399-413
Authors: Kelly K, Swords R, Mahalingam D, Giles FJ
Imatinib is broadly used in the frontline treatment of chronic myeloid leukemia (CML). Although long-term safety and efficacy have been established, some patients will not respond to imatinib. Nilotinib and dasatinib successfully recapture responses for most patients with imatinib-refractory or -intolerant disease. These drugs have different safety profiles, which are likely associated with their divergent inhibitory targets. The presence of Bcr-Abl mutations and safety profiles of available therapies in relation to patient history should be considered when choosing a second-line agent. This review evaluates the safety and tolerability of agents approved for CML treatment and briefly discusses newer third-line agents.
PMID: 20528247 [PubMed - indexed for MEDLINE]
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