scholarly journals Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 4839-4842 ◽  
Author(s):  
Elias Jabbour ◽  
Hagop M. Kantarjian ◽  
Dan Jones ◽  
Neeli Reddy ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Kinase Domain ◽  
Disease Stage ◽  
Kinase Domain Mutation

Abstract Mutations in codon 317 after treatment with imatinib and dasatinib have been reported. We reviewed patients with chronic myeloid leukemia and mutations after tyrosine kinase inhibitor (TKI) therapy. F317L was detected in 20, including 12/99 (12%) with mutation after imatinib failure, and 8/16 (50%) after dasatinib (P = .001). Median follow-up from mutation detection was 25 months. At the time of F317L, 8 patients were in chronic phase (CP), 6 in accelerated phase, and 6 in blast phase. There was no difference in characteristics between patients with or without F317L mutations, or with no mutations. A complete cytogenetic response was acheived in 3 of 6 patients treated with nilotinib, 2 of 2 with imatinib, and 0 of 3 with dasatinib. Survival of patients with F317L was similar to those with other mutations (P = .45). Patients in CP had better outcome, with a 2-year survival of 75%. F317L mutation is resistant to dasatinib but sensitive to other TKIs. The prognosis is dependent mostly on the disease stage.

BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1208-1215 ◽  
Author(s):  
Simona Soverini ◽  
Andreas Hochhaus ◽  
Franck E. Nicolini ◽  
Franz Gruber ◽  
Thoralf Lange ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Mutation Analysis ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Direct Sequencing ◽  
Chronic Phase ◽  
Kinase Domain ◽  
Abl Kinase

AbstractMutations in the Bcr-Abl kinase domain may cause, or contribute to, resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia patients. Recommendations aimed to rationalize the use of BCR-ABL mutation testing in chronic myeloid leukemia have been compiled by a panel of experts appointed by the European LeukemiaNet (ELN) and European Treatment and Outcome Study and are here reported. Based on a critical review of the literature and, whenever necessary, on panelists' experience, key issues were identified and discussed concerning: (1) when to perform mutation analysis, (2) how to perform it, and (3) how to translate results into clinical practice. In chronic phase patients receiving imatinib first-line, mutation analysis is recommended only in case of failure or suboptimal response according to the ELN criteria. In imatinib-resistant patients receiving an alternative TKI, mutation analysis is recommended in case of hematologic or cytogenetic failure as provisionally defined by the ELN. The recommended methodology is direct sequencing, although it may be preceded by screening with other techniques, such as denaturing-high performance liquid chromatography. In all the cases outlined within this abstract, a positive result is an indication for therapeutic change. Some specific mutations weigh on TKI selection.

scholarly journals Ponatinib induced improvement of cutaneous lesions associated to accelerated phase of Ph-positive chronic myeloid leukemia

2016 ◽  
Vol 8 ◽  
pp. 2016016
Author(s):  
Massimo Breccia ◽  
Gioia Colafigli ◽  
Luisa Quattrocchi ◽  
Elisabetta Abruzzese ◽  
Giuliana Alimena
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Kinase Domain ◽  
Third Generation ◽  
Cutaneous Lesions ◽  
Advanced Phase ◽  
Kinase Domain Mutation

Ponatinib a third generation tyrosine kinase inhibitor, has been approved for all phases of disease in CML. In advanced phase, has been confirmed with a good efficacy in all type of resistance, including T315I kinase domain mutation. We here report activity of the drug in advanced phase with extramedullary localization.

scholarly journals Allografting for Bosutinib, Imatinib, Nilotinib, Dasatinib, and Interferon Resistant Chronic Myeloid Leukemia without ABL Kinase Mutation

2011 ◽  
Vol 2011 ◽  
pp. 1-4
Author(s):  
B. Uz ◽  
O. Bektas ◽  
E. Eliacik ◽  
H. Goker ◽  
Y. Erbilgin ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Kinase Domain ◽  
Current Treatment ◽  
Hematopoietic Stem ◽  
Abl Kinase ◽  
Kinase Domain Mutation ◽  
Kinase Mutation

The current treatment of chronic phase chronic myeloid leukemia (CML) consists of oral tyrosine kinase inhibitors (TKIs). However, high-risk CML may present with an aggressive course which may result in blastic crisis or a “difficult-to-manage” state with available treatments. The aim of this paper is to report a patient with complicated CML resistant to treatment and progressed despite the administration of bosutinib, imatinib mesylate, nilotinib, dasatinib, interferon alpha 2a, cytotoxic chemotherapy, and allogeneic hematopoietic stem cell transplantation. The striking point of this case story is that no Abl kinase domain mutation against TKIs has been detected during this very complicated disease course of CML. Meanwhile, challenging cases will always be present despite the hope and progress in CML in the TKI era.

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.

scholarly journals Tyrosine Kinase Inhibitor Therapy for Chronic Myeloid Leukemia: Approach to Patients with Treatment-Naive or Refractory Chronic-Phase Disease

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Catherine C. Smith ◽  
Neil P. Shah
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Rapid Development ◽  
Chronic Phase ◽  
The United States ◽  
Medical Needs ◽  
Treatment Naïve

Abstract The 21st century ushered in the dawn of a new era of targeted therapeutics and a dramatic shift in the management of chronic-phase chronic myeloid leukemia (CP-CML) patients. Groundbreaking scientific and translational studies have led to the rapid development and approval of several effective BCR-ABL tyrosine kinase inhibitors (TKIs). In the United States, there are currently 3 approved BCR-ABL TKIs for newly diagnosed CP-CML patients. It is anticipated that clinical outcomes will continue to improve as more TKIs that address unmet medical needs are approved. However, to achieve this goal, it is critical to carefully monitor and optimally manage patients. To this end, the latest seminal clinical trial results of approved and investigational BCR-ABL TKIs and some of the salient unique features of each of these agents are summarized herein.

Chronic myeloid leukemia with p190BCR-ABL: prevalence, morphology, tyrosine kinase inhibitor response, and kinase domain mutation analysis

Blood ◽  
2009 ◽  
Vol 114 (16) ◽  
pp. 3502-3503 ◽  
Author(s):  
Animesh Pardanani ◽  
Ayalew Tefferi ◽  
Mark R. Litzow ◽  
Clive Zent ◽  
William J. Hogan ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Mutation Analysis ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Kinase Domain ◽  
Kinase Domain Mutation

scholarly journals Complications of Tyrosine Kinase Inhibitors Therapy in Chronic Myeloid Leukemia - Chronic Phase

2019 ◽  
Vol 70 (8) ◽  
pp. 3017-3020
Author(s):  
Despina Calamar Popovici ◽  
Ioana Ionita ◽  
Mirela Nedelcu ◽  
Claudiu Ionita ◽  
Hortensia Ionita ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Anthropometric Parameters ◽  
Tyrosine Kinase Inhibitor Therapy ◽  
Initiation Of Therapy

Chronic myeloid leukaemia is a malignant tumor of pluripotent haemopoetic stem cell, characterized by increase granulocytes with left shift and the presence of the Ph chromosome.Treatment of chronic phase is made with tyrosine kinase inhibitors administered orally and can have secondary effects: haematological and non-haematological. The purpose of this paper is to assess complications of tyrosine kinase inhibitor therapy in chronic phase of chronic myeloid leukemia and establishing correlations with the type of inhibitor used. The study was performed on a total of 140 patients diagnosed with chronic phase CML in the Hematology Department of the City Clinical Emergency Hospital Timisoara between January 2006 - January 2016. The lot proposed has been studied in terms of anthropometric parameters and also the haematological and biochemical. It showed complications after initiation of therapy with tyrosine kinase inhibitors and also the correlations statistically significant between complications and type of inhibitor used. The study reveals that regardless the type of inhibitor used both haematological complications arise and non haematological. The most common are: neutropenia, thrombocytopenia, anemia, fluid retention, muscle and joint pain. Less common are nausea, diarrhea, abdominal pain, increased liver enzymes. Despite complications of occurring, these modern therapies significantly improve both survival and quality of life of patients.

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