Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In these last years the use of alpha-interferon (alpha-IFN) has received increasing attention especially in the onco-haematological field. alpha-IFN is particularly useful in the treatment of hairy cell leukemia, cryoglobulinemia, multiple myeloma and myeloproliferative syndromes (SMP). Among these latter conditions alpha-IFN must be considered as the treatment of choice of the early chronic phase of chronic myelogenous leukemia (LMC) in patients not eligible for allogenic bone marrow transplantation because its ability to induce a greater number of clinical remission and cytogenetic responses when compared to the classical chemotherapeutic agents. A myelosuppressive, non-leukemogenic effect and a more selective activity on the neoplastic hemopoiesis appear to be the most important advantages of alpha-IFN therapy. Based on the results obtained in LMC the use of alpha-IFN has been extended to the other SMP, essential thrombocytemia (TE), polycythemia vera (PV), idiopathic myelofibrosis with myeloid metaplasia (MMM). alpha-IFN is able to control thrombocytosis which often characterize the SMP so it appears to be particularly effective in TE. Actually a relatively limited literature is available about the alpha-IFN treatment of PV and MMM and so it is difficult to draw a final conclusion about the effectiveness of the treatment in these disorders. However, especially in PV, the use of this cytokine appears to be promising. The latest reports of the literature are here summarized and discussed.
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PMID:[Interferon-alpha in the treatment of myeloproliferative syndromes]. 785 89

During the last decade, imatinib was current gold standard treatment of chronic myelogenous leukemia (CML), showing a great effectiveness. Thus, the Therapeutic Drug Monitoring (TDM), rarely applied in clinical oncology practice, did not appear necessary at the moment. However, the absence of response among patients and the metabolic profile of imatinib (involving the CYP3A4) suggested the existence of a great interindividual variability. During the last 4 years, studies about the pharmacokinetic/pharmacodynamic relationship have confirmed this variability and highlighted a relation between the trough concentrations of imatinib and the clinical response. An effectiveness threshold, close to 1000 ng/mL, seems to be correlated with better cytogenetic and molecular responses. Consequently, TDM could assist in investigation of the observance, the absence of response, the drug-drug interactions, but the proof of its utility requires complementary studies. In conclusion, the level of proof of imatinib TDM in LMC varies between levels "recommended" and "potentially useful".
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PMID:[Therapeutic drug monitoring of tyrosine-kinase inhibitors in the treatment of chronic myelogenous leukaemia: interests and limits]. 2069 73

During the last decade, imatinib was current gold standard treatment of chronic myelogenous leukemia (CML), showing a great effectiveness. Thus, the Therapeutic Drug Monitoring (TDM), rarely applied in clinical oncology practice, did not appear necessary at the moment. However, the absence of response among patients and the metabolic profile of imatinib (involving the CYP3A4) suggested the existence of a great interindividual variability. During the last 4 years, studies about the pharmacokinetic/pharmacodynamic relationship have confirmed this variability and highlighted a relation between the trough concentrations of imatinib and the clinical response. An effectiveness threshold, close to 1000 ng/mL, seems to be correlated with better cytogenetic and molecular responses. Consequently, TDM could assist in investigation of the observance, the absence of response, the drug-drug interactions, but the proof of its utility requires complementary studies. In conclusion, the level of proof of imatinib TDM in LMC varies between levels "recommended" and "potentially useful".
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PMID:[Not Available]. 2739 89

In the context of chronic myeloid leukemia (CML) resistant to tyrosine kinase inhibitors (TKIs), BCR-ABL1 tyrosine kinase domain (TKD) mutations still remain the sole biological marker that directly condition therapeutic decision. These recommendations aim at updating the use of BCR-ABL1 mutation testing with respect to new available therapeutic options and at repositioning different testing methods at the era of next generation sequencing (NGS). They have been written by a panel of experts from the French Study Group on CML (Fi-LMC), after a critical review of relevant publications. TKD mutation testing is recommended in case of treatment failure but not in case of optimal response. For patients in warning situation, mutation testing must be discussed depending on the type of TKI used, lasting of the treatment, kinetic evolution of BCR-ABL1 transcripts along time and necessity for switching treatment. The kind and the frequency of TKD mutations occasioning resistance mainly depend on the TKI in use and disease phase. Because of its better sensitivity, NGS methods are recommended for mutation testing rather than Sanger's. Facing a given TKD mutation, therapeutic decision should be taken based on in vitro sensitivity and clinical efficacy data. Identification by sequencing of a TKD mutation known to induce resistance must lead to a therapeutic change. The clinical value of testing methods more sensitive than NGS remains to be assessed.
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PMID:[Recommendations from the French CML Study Group (Fi-LMC) for BCR-ABL1 kinase domain mutation analysis in chronic myeloid leukemia]. 3135 36

There are few areas in medicine in which patient-parent advocacy groups play such a central and prominent role as in the field of rare diseases. As illustrated by the French Association of Chronic Myeloid Leukemia (LMC France), its contribution is not only focused on its role as participants or key informant related to clinical studies but also on drug information and drug safety. The discovery of tyrosine kinase inhibitors against the BCR-ABL1 oncogenic fusion protein has revolutionized the management of CML, becoming a chronic illness rather than a life-threatening disease. Because ensuring ongoing well-being requires some knowledge, LMC France has built, in synergy with healthcare professionals from its scientific council, a CML-specific, patient-friendly knowledge base including resources and knowledge related to drug information (drug development, generics, pharmacovigilance) and drug safety using several educational tools such as videos, CML support, and CML drug sheets. To disseminate more largely, an e-university learning for regional key informants from LMC France and also CML patients and their caregivers was launched, including a large resources related to drug information and drug safety in synergy with hematologists and clinical pharmacologists.
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PMID:Patients' organizations in rare diseases and involvement in drug information: Illustrations with LMC France, the French Association of Chronic Myeloid leukemia. 3211 87