Leukemia Research Paper

COMPARATIVE STUDY OF EFFICACY AND TOXICITY OF IMATINIB AND NILOTINIB BASED REGIMENS IN CML PATIENTS

ABSTRACT:

CML, a type of myeloproliferative disorder in which proliferation of bone marrow stem cells is found. Chronic phase, accelerated phase & blast crises are 3 phases of CML.Overall 90% of patients with CML Philadelphia chromosomes are present as a result of a t (9; 22) reciprocal translocation. This chromosomal abnormality is detected by cytogenetics, FISH (fluorescent in situ hybridization). BCR -ABL contains a protein that plays an important role in development of leukemia & it is BCR-ABL oncogene. Imatinib & Nilotinib are used for its treatment. Imatinib mesylate (Glivec, Novartis), a potent competitive inhibitor of the tyrosine kinase

Leukemia is best described by increased, unregulated growth of myeloid cells in the bone marrow and assembly of these cells in the blood. A bone marrow disease majorly due to multiplication of mature granulocytes i.e neutrophils,eosinophils & basophils & their precursors. Chronic myeloid leukemia (CML) is a type of myeloproliferative disorder, associated with characteristic translocation called the Philadelphia (ph) chromosome [1]. In this chromosomal translocation, parts of two chromosomes (the 9th and 22nd) shift their places. [1] Consequently, part of the BCR i.e. breakpoint cluster gene from chromosome 22 is fused with the ABL gene on chromosome 9. (Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a protein that, in humans, is encoded by the ABL gene). It results in the bone marrow making an enzyme, called tyrosine kinase, that results in too many stem cells to become white blood cells (granulocytes or blasts) CML has three phases. Respectively, each phase of CML is elucidated on the basis of number of blast cells in the blood &bone marrow.Chronic phase,accelerated phase,blast crises are the main stages of CML [2]. Authentic treatment for CML is a bone marrow transplant or an stem cell transplant.Rather there are also four major ways of treatment in CML such as treatment with tyrosine kinase inhibitors(TKI), myelosuppressive or

The analysis of data demonstrated that patients belonging to different age groups taking imatinib and nilotinib have a continuous increase in their hemoglobin level. This shows our data is not in harmony with previous findings that, anemia is a main dose dependent side effect of imatinib and nilotinib. Increase in Hb values might be due to some concomitant use of iron therapy; ESAs, PCV etc. white blood cells count is also an important parameter to determine effectiveness of both drugs, results indicate that there is decrease in number of white blood cells during course of therapy. Platelets number in different age groups, taking imatinib, showed some irregularity while data obtained for patients taking nilotinib showed high variations. Neutrophils count is increasing and decreasing with irregularity in patients taking imatinib while neutrophils count in nilotinib therapy, in all age groups, is first decreasing and then again increasing. In general, lymphocyte count is increasing in both treatment groups but in some age groups irregularity has also been observed. There is a continuous rise and fall in monocyte number with both drugs. Eosinophils values are almost constant with imatinib but show decline with nilotinib. (graph 2,3) These findings are indicative of myelo-suppressive effect of imatinib and