One-year and longer-term molecular responses to nilotinib and dasatinib for newly diagnosed chronic myeloid leukemia: A matching-adjusted indirect comparison.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 7072-7072
Author(s):  
James E. Signorovitch ◽  
Eric Qiong Wu ◽  
Keith A. Betts ◽  
William M. Reichmann ◽  
Darren Thomason ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Indirect Comparison ◽  
Newly Diagnosed ◽  
Molecular Responses ◽  
Adjusted Indirect Comparison ◽  
One Year

Detection of BCR-ABL gene in Chronic Myeloid Leukemia patients treated with Tyrosine Kinase Inhibitors Drugs by Gene Expert System

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Maysaa Ali Abdul Khaleq ◽  
Hussein Ali Saheb ◽  
Ahmed M Sultan ◽  
Mohsen A. N Alrodhan
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Molecular Technique ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
The Mean ◽  
One Year ◽  
Wbc Count ◽  
Rna Transcript

Chronic myeloid leukemia (CML) is one of human malignancies caused by genetic mutation and chromosomal translocation, a BCR-ABL fusion gene and as result Philadelphia chromosome is formed. The irregular tyrosine kinase activity of encoded protein by this gene causes the establishment of the disease. Nilotinib are potent and well inhibitor for BCR-ABL tyrosine kinase. This study was conducted at the period from September 2016 to February 2017,100 Iraqi CML patients were divided into two groups, first group of 50 patients were received Imatinib 400-800 mg/day, second group of another 50 patients were received 800 mg/day Nilotinib, WBC were microscopically counted using improved Neubauer ruled hemocytometer counting chamber.BCR-ABL gene RNA transcript and endogenous control (house keeping gene ) RNA transcript were extracted and purified and then reverse transcripted to cDNA after that the product was amplified and quantified by q RT-PCR. The results first group patients distribution according to the gender were 56% and 44% for males and females respectively while the mean age of the patients was 45.82 ± 16.17,the result of WBC counting of this group in regard to disease duration showed that the highest value was observed in newly diagnosed and advanced stage 98.28 ± 89.28,77.11± 2.98 respectively.The WBC count return to normal level after the period of treatment with Imatinib with significant reduction after one year at p≤ 0.0001.The results of molecular technique and BCR-ABL analysis in newly diagnosed, advanced stage and cytogenetic failure patients were 10.05 ± 4.7,3.03± 0.94 and 28.4±0.09 respectively with significant decrease after one year of treatment at p ≤ 0.002.On the other hand the results of the second group of CML patients in relation to the gender were 45% and 55% of males and femalesrespectively,while the mean age group was 36.68 ±13.51. The results of WBC count according to disease distribution in newly diagnosed and advanced stage were 87.5 ± 8.71 and43±21.72 respectively. WBC count was return to normal level after one year of treatment with Nilotinib with significant decrease at p≤0.0001. While the molecular technique and BCR-ABL analysis in newly diagnosed, advanced stage and cytogenetic failure group were 7.77±4, 1, 16.17 ± 3.78 and 2.02±0.53 after one year of treatment with Nilotinib with significant decrease at p≤ 0.0001. We conclude that treatment with Imatinib was found tough in a high extent of patients, Nilotinib is extending specific tyrosine kinaseinhibitor possess greater and selectively activity for BCR-ABL.

Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 3965-3973 ◽  
Author(s):  
Timothy P. Hughes ◽  
Susan Branford ◽  
Deborah L. White ◽  
John Reynolds ◽  
Rachel Koelmeyer ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Dose Escalation ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Cytogenetic Response ◽  
Initial Therapy ◽  
Newly Diagnosed ◽  
Molecular Responses ◽  
Daily Average

Abstract We conducted a trial in 103 patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) using imatinib 600 mg/day, with dose escalation to 800 mg/day for suboptimal response. The estimated cumulative incidences of complete cytogenetic response (CCR) by 12 and 24 months were 88% and 90%, and major molecular responses (MMRs) were 47% and 73%. In patients who maintained a daily average of 600 mg of imatinib for the first 6 months (n = 60), MMR rates by 12 and 24 months were 55% and 77% compared with 32% and 53% in patients averaging less than 600 mg (P = .037 and .016, respectively). Dose escalation was indicated for 17 patients before 12 months for failure to achieve, or maintain, major cytogenetic response at 6 months or CCR at 9 months but was only possible in 8 patients (47%). Dose escalation was indicated for 73 patients after 12 months because their BCR-ABL level remained more than 0.01% (international scale) and was possible in 45 of 73 (62%). Superior responses achieved in patients able to tolerate imatinib at 600 mg suggests that early dose intensity may be critical to optimize response in CP-CML. The trial was registered at www.ANZCTR.org.au as #ACTRN12607000614493.

scholarly journals IMATINIB IN CHRONIC MYELOID LEUKEMIA: AN OVERVIEW

2013 ◽  
Vol 6 (1) ◽  
pp. e2014007 ◽  
Author(s):  
Tomasz Sacha
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Randomized Study ◽  
Leukemic Cell ◽  
Cytogenetic Response ◽  
Kinase Domain ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
One Year

Imatinib was the first signal transduction inhibitor (STI), used in a clinical setting. It prevents a BCR-ABL protein from exerting its role in the oncogenic pathway in chronic myeloid leukemia (CML). Imatinib directly inhibits the constitutive tyrosine kinase activity. Imatinib binds to BCR-ABL kinase domain by preventing the transfer of a phosphate group to tyrosine on the protein substrate and the subsequent activation of phosphorylated protein. As the result, the transmission of proliferative signals to the nucleus is blocked and leukemic cell apoptosis is induced. The FDA has approved imatinib as first-line treatment for newly diagnosed CML in December 2002 following an International Randomized Study (IRIS), initiated in June 2000, comparing imatinib at a single daily dose 400 mg to IFN alpha plus cytarabine in newly diagnosed patients with CML in CP. Results from this study show the outstanding effectiveness of imatinib and its superiority with respect to the rates of complete hematological response (CHR), major and complete cytogenetic response (MCyR, CCyR). Patients randomized to imatinib arm at 8 – year data cut off continue to have a durable hematologic and cytogenetic response, low progression rates to AP or BC, and remarkable survival outcomes. An overall survival (OS) rate is 85% for patients receiving imatinib (93% when only CML-related deaths and those prior to stem cell transplantation are considered). The results have been confirmed in the last years by several groups. According these cumulative results the rates of CCyR achieved after one year of therapy with imatinib at standard dose ranged from 49% to 77%, and the proportion of patients who achieved major molecular response (MMR) after one year ranged between 18% and 58%. Discontinuation of imatinib has been also tried in patients in MMR, a molecular relapse occurs in about one third of patients, generally within 6 months from imatinib cessation.

Frequency of Major Molecular Responses to Imatinib or Interferon Alfa plus Cytarabine in Newly Diagnosed Chronic Myeloid Leukemia

2003 ◽  
Vol 349 (15) ◽  
pp. 1423-1432 ◽  
Author(s):  
Tim P. Hughes ◽  
Jaspal Kaeda ◽  
Susan Branford ◽  
Zbigniew Rudzki ◽  
Andreas Hochhaus ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Interferon Alfa ◽  
Newly Diagnosed ◽  
Molecular Responses
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