Am J Leuk Res | Volume 2, Issue 2 | Research Article | Open Access

Effect of Tyrosine Kinase Inhibitor in Patients with Chronic Myeloid Leukemia (Cytogenetic, Molecular response) in Mosul-Iraq

Khalid Kheroo*

Department of Leukemia Research, University of Mosul, Iraq

*Correspondance to: Khalid Kheroo 

Fulltext PDF

Abstract

Objective: To evaluate the cytogenetic, molecular response, effect particularly on bone and heart for imatinib and nilotinib respectively in patients with chronic myeloid leukemia.
Methods: the study was conducted on eighty seven patients on imatinib and twenty nine patients on nilotinib as second line treatment who were treated at Ibn-sena teaching hospital /outpatient hematology department were reviewed from April 2002 to April 2014. Eligible patients were 18 years or older, mean age 41.17 year (range 18-75 year), 42 male and 45 female all are in chronic phase CML. The 29 patients on nilotinib, of them 16 were male and 13 were female mean age 43 year (range 25-70 years) initially treated by imatinib and switched to nilotinib due to primary, secondary failure or drug intolerance. The FISH analysis was carried on at central authorized laboratory in Baghdad. The RT-PCR carried on authorized laboratory initially in Baghdad then in Mosul, (both laboratory using the same standard and sponsored by Novartis). To study the effect of imatinib mesylate on bone mineral density fifty out of 87 patients were enrolled for this purpose. For all the patients ionized calcium, total calcium, serum albumin, and serum alkaline phosphatase, serum phosphate, and urea, creatinine and serum levels of intact parathyroid hormone measured at baseline, 6 months and 12 months. Dual Energy X-ray Absorptiometry (DEXA) measurements of the lumbar spine (L2–L4 vertebrae), and femoral neck were performed using a DEXA scanner. For the nilotinib group, all patients had a base-line standard 12-lead Electrocardiography (ECG), with a follow-up ECG’s performed every 6 months during the study period to assess any occurrence of QT prolongation, ischemic changes, or arrhythmias. Noninvasive cardiac imaging was performed using the resting transthoracic Echocardiography (Echo) with its 2-dimentional and M-mode views.
Results: The median duration of CML is 8 years (range 4-12) and the median duration of treatment by the first generation of the brand tyrosine kinase inhibitor is 8 years (range 4-12). Of the 87 patients who were eligible for follow up 86 (98.8%) achieved complete and major cytogenetic response and 86.21% have complete and major molecular response. For those on nilotinb 68.94% have complete and major cytogenetic and molecular response. The overall survival rate is 86.20% at 12 year of imatinib therapy. The 5 years survival rate after nilotinib treatment is 68.94% (20 out of 29). DEXA analysis revealed no significant changes in L2–L4 lumbar vertebral Bone Mineral Density (BMD) but there is significant change at femoral neck. Prolongation of QTcF was observed in 80% of patients on nilotinib with a mean of 13.56 milli second. There were no significant difference in left ventricular ejection fraction % from the baseline and none of the patient develop major cardiac event.
Conclusion: Complete and major molecular response is 86.20% on imatinib therapy where as it is 68.94% on nilotinib as second line therapy. The overall survival rate is 86.20% at 12 year of imatinib therapy. The 5 years survival rate after nilotinib treatment is 68.94%. Significant decrease in femoral neck Bone Mineral Density (BMD) observed after 12 month time point. Nilotinib prolonged the QTcF interval by an average of 13.56 milli second with no adverse cardiac events.

Citation:

Kheroo K. Effect of Tyrosine Kinase Inhibitor in Patients with Chronic Myeloid Leukemia (Cytogenetic, Molecular response) in Mosul-Iraq. Am J Leuk Res. 2018;2(2):1014.

Subscribe to Our Newsletter