scholarly journals Tyrosine kinase inhibitor–induced platelet dysfunction in patients with chronic myeloid leukemia

Blood ◽  
2009 ◽  
Vol 114 (2) ◽  
pp. 261-263 ◽  
Author(s):  
Alfonso Quintás-Cardama ◽  
Xin Han ◽  
Hagop Kantarjian ◽  
Jorge Cortes
Keyword(s):  
Platelet Aggregation ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Platelet Dysfunction ◽  
Normal Platelet ◽  
Closure Time ◽  
Platelet Aggregometry ◽  
Increased Risk

Abstract Dasatinib is associated with increased risk of bleeding among patients with chronic myeloid leukemia, even in the absence of thrombocytopenia, suggesting the presence of a hemostatic defect. We tested platelet aggregation in 91 patients with chronic myeloid leukemia in chronic phase either off-therapy (n = 4) or receiving dasatinib (n = 27), bosutinib (n = 32), imatinib (n = 19), or nilotinib (n = 9). All but 3 patients simultaneously receiving imatinib and warfarin had normal coagulation studies. All 4 patients off therapy had normal platelet aggregation. Impaired platelet aggregation on stimulation with arachidonic acid, epinephrine, or both was observed in 70%, 85%, and 59% of patients on dasatinib, respectively. Eighty-five percent of patients on bosutinib, 100% on nilotinib, and 33% on imatinib had normal platelet aggregation. Dasatinib 400 nM induced rapid and marked prolongation of closure time to collagen/epinephrine in normal whole blood on the PFA-100 system. In conclusion, dasatinib and, to some extent, imatinib produce abnormalities in platelet aggregometry testing.

scholarly journals Chronic myeloid leukemia: successful therapy with nilotinib in a young patient with high Sokal risk and in sub-optimal response with imatinib

2015 ◽  
Vol 4 (6S) ◽  
pp. 13-16
Author(s):  
Fausto Palmieri
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Young Patient ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Kinase Inhibitor ◽  
Standard Dose ◽  
Chronic Phase ◽  
Molecular Response ◽  
Optimal Response ◽  
Increased Risk

Here we describe a case of a young patient with chronic myeloid leukemia, at high-risk according to the Sokal index, who started imatinib at standard dose and obtained a sub-optimal response at 12 months. This condition was not automatically an indication to change therapy, but considering the patient as suboptimal, we decided to switch to a second-generation tyrosine kinase inhibitor (TKI), nilotinib 800 mg/die, obtaining soon a complete cytogenetic response (CCYR), thereafter a major molecular response (MMolR). Delayed achievement of cytogenetic and molecular is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving imatinib therapy. Therefore we can hypothesise that this kind of patient could be elegible for an early switch to second-generation TKI.

scholarly journals Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3403-3412 ◽  
Author(s):  
H. Jean Khoury ◽  
Jorge E. Cortes ◽  
Hagop M. Kantarjian ◽  
Carlo Gambacorti-Passerini ◽  
Michele Baccarani ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Cytogenetic Response ◽  
Abl Tyrosine Kinase ◽  
Kaplan Meier

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier–estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.

Mutation Analysis of ABL1 Gene and its Relation to the Achievement of Major Molecular Response in Indonesian Chronic Myeloid Leukemia Patients

2020 ◽  
Vol 17 (1) ◽  
pp. 48-54
Author(s):  
Reni Widyastuti ◽  
Melva Louisa ◽  
Ikhwan Rinaldi ◽  
Riki Nova ◽  
Instiaty Instiaty ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Kinase Domain ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Cross Sectional ◽  
Imatinib Resistance

Background: Imatinib mesylate is the first tyrosine kinase inhibitor approved for chronic myeloid leukemia (CML) therapy. Imatinib is an effective drug. However, previous studies have shown that about 20-30% of patients eventually would develop resistance to imatinib. Approximately 40% of imatinib resistance is associated with BCRABL kinase domain mutation. One of the most common and serious variations account for imatinib response is T315I of ABL1 gene. Objective: The study aimed to examine the association of T315I mutation with the ABL1 gene and its relation to major molecular response (MMR) achievement in CML patients. This study also examined other mutations adjacent to T315I, i.e., F311I, F317L, and different possible variations in the ABL1 gene. Methods: This was a cross-sectional study on Indonesian CML patients in chronic phase. We analyzed 120 blood samples from patients in chronic phase who have received imatinib mesylate (IM) for ≥12 months. Results: There were no T315I, F311I, and F317L mutations found in this study. However, we found another variation, which was 36 substitutions from A to G at position 163816 of ABL1 gene (according to NG_012034.1). Conclusions: We found no T315I, F311I, and F317L mutations in this study. Our findings suggest that there might be other factors that influenced the MMR achievement in our study patients. However, there were 36 substitutions from A to G at position 163.816 (according to NG_012034.1) that needed further examination to explore the significance of this mutation in clinical practice.

scholarly journals A Retrospective Analysis about Frequency of Monitoring in Italian Chronic Myeloid Leukemia Patients after Discontinuation

2020 ◽  
Vol 9 (11) ◽  
pp. 3692
Author(s):  
Matteo Dragani ◽  
Giovanna Rege Cambrin ◽  
Paola Berchialla ◽  
Irene Dogliotti ◽  
Gianantonio Rosti ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Molecular Response ◽  
Molecular Monitoring ◽  
Delay In Diagnosis ◽  
Number Of Patients

Successful discontinuation of tyrosine kinase inhibitors has been achieved in patients with chronic-phase chronic myeloid leukemia (CML). Careful molecular monitoring after discontinuation warrants safe and prompt resumption of therapy. We retrospectively evaluated how molecular monitoring has been conducted in Italy in a cohort of patients who discontinued tyrosine kinase inhibitor (TKI) treatment per clinical practice. The outcome of these patients has recently been reported—281 chronic-phase CML patients were included in this subanalysis. Median follow-up since discontinuation was 2 years. Overall, 2203 analyses were performed, 17.9% in the first three months and 38.4% in the first six months. Eighty-six patients lost major molecular response (MMR) in a mean time of 5.7 months—65 pts (75.6%) during the first six months. We evaluated the number of patients who would experience a delay in diagnosis of MMR loss if a three-month monitoring schedule was adopted. In the first 6 months, 19 pts (29.2%) would have a one-month delay, 26 (40%) a 2-month delay. Very few patients would experience a delay in the following months. A less intense frequency of monitoring, particularly after the first 6 months off treatment, would not have affected the success of treatment-free remission (TFR) nor put patients at risk of progression.

Recurrent bone marrow aplasia secondary to nilotinib in a patient with chronic myeloid leukemia: A case report

2012 ◽  
Vol 18 (4) ◽  
pp. 440-444 ◽  
Author(s):  
Prathima Prodduturi ◽  
Anamarija M Perry ◽  
Patricia Aoun ◽  
Dennis D Weisenburger ◽  
Mojtaba Akhtari
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Bone Marrow Aplasia ◽  
Line Therapy ◽  
Grade 3

Nilotinib is a potent tyrosine kinase inhibitor of breakpoint cluster region-abelson (BCR-ABL), which has been approved as front-line therapy for newly diagnosed chronic myeloid leukemia in chronic phase and as second-line therapy after imatinib failure in chronic or accelerated phase chronic myeloid leukemia. Tyrosine kinase inhibitors have been associated with myelosuppression and grade 3 or grade 4 cytopenias are not uncommon in chronic myeloid leukemia patients treated with these drugs. There are a few reports of imatinib-associated bone marrow aplasia, but to our knowledge only one reported case of bone marrow aplasia associated with nilotinib. Herein, we report a 49-year-old male patient with chronic phase chronic myeloid leukemia, who developed severe bone marrow aplasia due to nilotinib. Possible mechanisms for this significant adverse drug reaction are discussed along with a review of literature.

Sign in / Sign up

Export Citation Format

Share Document