الفهرس | Only 14 pages are availabe for public view |
Abstract Chronic myeloid leukemia (CML) is a hematological disorder of myeloid progenitor cells. It generally presents with leukocytosis along with accumulation of myelocytes and neutrophils due to uncontrolled over production. The etiology of CML is complex and has been associated with excessive exposure to radiation.The diagnosis of CML is based on the presence or absence of an abnormally translocated chromosome called Philadelphia chromosome (Ph). As a result of this translocation oncogene ABL1 from chromosome 22 moves to the BCR gene on chromosome 9 and BCR gene moves to ABL1position, leading to the formation of BCR/ABL1 kinase. The resultant defective tyrosine kinase stimulates the uncontrolled proliferation of cells resulting in reduced apoptosis causing genomic instabilityIn the absence of treatment, CML progresses within several years from a chronic phase to an accelerated phase, and eventually culminates in blastic phase and death As a treatment option, targeted inhibitor of tyrosine kinase (TKI) such as imatinib mesylate (Glivec) was used for the treatment of CML which contests with ATP in binding the BCR-ABL (and ABL) protein kinase. Initially it provided sustained molecular remission in CML patients but up to 33% of patients developed resistance and/or loss of response due to mutations and pharmacokinetic variability.Nilotinib (Tasigna) is a 2nd generation TKI which overcomes the resistance and loss of response issue and achieves good tolerability and response against Ph positive CML. It is an aminophenylpyrimidine derivative with higher selectivity for BCR ABL1 kinase and is approved by the European Medicines Agency (EMA) and the Food and Drug Administration, USA (FDA) as first line treatment for CML due to quicker, deeper and sustained cytogenetic and molecular responses The sequence and timing of morphologic and cytogenetic changes in CML patients during therapy in a long-time has not been described. Also, platelet count, blood percentage of blasts, basophils and other hematologic elements are the prognostic factors for CML treatment failure The aim of the present study was to determine the effects of tyrosine kinase inhibitors (Imatinib & Nilotinib) on liver enzymes and electrolytes in relation to hematologic response in patients with chronic phase CML This was prospective study, was conducted on Thirty-eight patients with CML referred to internal medicine department, hematology unit, Assiut University Hospital, Assiut, Egypt during the period from January 2020 till February 2022. |