الفهرس 
Chronic Myeloid Leukemia (CML)Only 14 pages are availabe for public view
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Abstract
CML is a clonal myeloproliferative neoplasm characterized by a specific translocation t (9; 22) (q34; q11). The novel chimeric protein BCR-ABL dictates the pathophysiology of the disease. The first TKI approved by the US FDA for treatment of Ph+ CP-CML was imatinib masylate (IM). Newer TKIs, nilotinib and dasatinib have been commercially available and were indicated for patients who developed resistance or intolerance to Imatinib. In 2010, both drugs became FDA approved as 1st line therapy in CP-CML. This is a retrospective analysis to compare efficacy and tolerability of dasatinib and nilotinib in achieving complete hematologic and molecular response in patients with chronic myelogenous leukemia resistant or intolerant to imatinib who started their treatment at Clinical Oncology and Nuclear Medicine department Tanta University Hospital and Tanta Cancer Center throughout the period from January 2013 till Decemper 2015 and its correlation with progression-free survival and overall survival. The primary end points were to assess response to TKI. The secondary end points were to assess PFS, OS safety and tolerability. The standard monitoring of response includes full blood counts, clinical examination and molecular examination by quantitative RTPCR for BCR-ABL mRNA. Assessment and monitoring minimal residual disease after treatment with both drugs had been done by Q RT-PCR. Thirty one patients (50.8%) were treated with nilotinib and thirty patients(49.2%) with dasatinib due to either failure of the treatment or intolerable side effects to imatinib. The median dose of nilotinib was 800mg/d (range from 400 to 800 mg/d , and 100 mg/d for dasatinib. Molecular response was statistically insignificant at 6, 12, 18 months between both groups with earlier and better response for patients treated with nilotinib. Regarding to age, molecular response was statistically significant at 6 months with better response for patients 40 years. Female patients had better molecular response at 6, 12,18 months but it was statistically insignificant. Normal splenic size, peripheral blast 10% and basophil count 20% had better molecular response. All the treated (61pts.) were followed for median time 31 (range 12-44) months. Seventeen patients developed progression of the disease within median26 (range 12-32) months. The 2-year PFS was 86.1%.According to line of treatment there was no statistical difference between nilotinib and dasatinib (p=0.823). There is significant difference between the two agents according to gender (p=0.009),nilotinib showed better results for females 89.7% vs. 80% for males (p=0.040). And dasatinib showed better response in female patients 88.5% vs.82.5% for males (p=0.061). According to age there was apparent benefit for patients aged 40y which was statistically significant(p=0.042). As regard splenic size, there was statistically insignificant difference between both groups(p=0.053) but with better results for normal sized spleen 90.2%Vs. 76% for enlarged size. According to the percent of peripheral blast there is apparent benefit for patients treated in both groups presented by blast cells< 10%which was statistically significant (p=0.013). For patients treated according to peripheral basophils, there is no significance with apparent equal results between both groups (p=0.178). For overall survival, Nine patients died throughout this period, seven(11.4%) patients died due to progression of the disease and 2(3,2%) patients died due to unrelated causes. The 2-year OS was 88.3%. Dasatinib show longer overall survival than nilotinib, 2 year OS 92.9% vs. 83.7% (p=0.295) with no statistically difference according to age, splenic size, peripheral blast and basophils. According to hematological complications including grade (3/4)neutropenia 3.2% Vs. 0.0% , grade (3/4) thrombocytopenia 3.2% Vs. 3.3% for nilotinib and dasatinib respectively. Non hematologic complications including rash and itching 0.0%vs. 10%, pericardial effusion 3.2% Vs. 10% ,pleural effusion 0% vs. 10.0%, and peripheral neuropathy 9.6% vs. 6.6% for nilotinib and dasatinib respectively.