الفهرس 
? Chronic Myeloid LeukemiaOnly 14 pages are availabe for public view
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Abstract
C
hronic myeloid leukemia (CML) is a clonal myeloproliferative expansion of transformed, primitive hematopoietic progenitor cells. It involves myeloid, monocytic, erythroid, megakaryocytic, B-lymphoid, and occasionally T-lymphoid lineages
CML is characterized by a balanced genetic translocation, t (9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome(ph).
About 50% of patients diagnosed with CML are asymptomatic, including weight loss, asthenia, fever, sweats, and malaise, in 40% of cases the diagnosis is based on abnormal blood counts and differential. Physical findings consist mainly splenomegaly in >50% of patients. The hallmark of diagnosis is leukocytosis with basophilia and with immature granulocytes, mainly metamyelocytes, myelocytes and promyelocytes, and few or occasional myeloblasts. Severe anemia is rare. Thrombocytosis is frequent,we can calculate prognostic scores for CML by Assess (SOKAL) score that need(Age, spleen size, platelet count and peripheral blood blasts),also peripheral blood esinophil and basopil percentage also required for(Hasford)score(Euro score. CML can be classified into three phases: chronic phase (CP), accelerated phase (AP), and blast phase (BP).
Until a little more than a decade ago, drug therapy for CML was limited to nonspecific agents such as busulfan, hydroxyurea(HU), and interferon-alfa (INF-a)
INF-a led to regression of the disease and improved survival but was hindered by a multitude of toxicities. Allogeneic stem cell transplantation (AlloSCT) was a curative intervention, but carried with it a high risk of morbidity and mortality.
The landscape changed dramatically with the development of small molecule tyrosine kinase inhibitors (TKIs) that were shown to potently interfere with the interaction between the BCR-ABL protein and adenosine triphosphate (ATP), blocking cellular proliferation of the malignant clone This “targeted” approach was found to dramatically alter the natural history.
Imatinib mesylate was the first TKI to receive for the treatment of patients with CML-chronic phase. It acts via competitive inhibition at the adenosine triphosphate (ATP)-binding site of the BCR-ABLprotein, which results in the inhibition of phosphorylation of proteins involved in cell signal transduction. It efficiently inhibits the BCR-ABL kinase, but also blocks the platelet-derived growth factor receptor (PGDFR), as well as the C-KIT tyrosine kinase.
Although the results using imatinib are quite impressive, only 55% of patients enrolled in international randomised study of interference (IRIS) remained on therapy at the 8-year follow up point. This underscored the need for additional options for patients who had failed or were intolerant to imatinib. This led to the rational development of 2nd generation TKIs with hopes they would effectively treat patients unable to continue on imatinib therapy.
Nilotinib is a potent and selective BCR-ABL1kinase inhibitor, which binds to the fusion protein via an additional lipophilic pocket adjacent to the ATP-binding site of ABL1 and is a 30-fold more potent inhibitor of BCR-ABL1 compared to imatinib.
The aim of the work is to assess the early reach ability of major molecular response (MMR) in chronic phase of CML patients on first(1st) and second(2nd) generation TKI(as regard 1st and 2nd line of treatment.
In this study, a retrospective study was done in the hematology unit at the department of internal medicine, Faculty of medicine, Ain Shams University on 100 CML patients, were sub divided into 3 groups Groups 1: included 40 patients on first generation TKI (imitinib 400mg), Groups 2 included 40 patients shifted from 1st generation (imitinib 400mg) to 2nd generation (nilotinib 300mg) Groups3included20 patients on 2nd generation (nilotinib) from the start.
All the patients were in chronic phase chronic myeloid leukemia, informed written consent was taken from all the patients for participation in this study.
All patients l groups withdrew blood samples for measurement of PCR for BCR-ABL.
The study data were collected from medical notes and laboratory data.
All patients were followed up for 1year.
After recording the results and using the suitable statistic methods, we found that
In our study, there was no statistically significant difference between age and sex and MMR.
In our study more patients with chronic myeloid leukemia in chronic phase achieve EMR on frontline nilotinib than imatinib.
In our study molecular and cytogenetic responses to nilotinib were superior to imatinib and more patients achieved undetectable levels of disease with nilotinib
At the end of our study, we suggest performing the study on a larger number of CML patients at different disease phases for longer duration.