scholarly journals Thrombotic microangiopathy in dasatinib-treated patients with chronic myeloid leukemia

2019 ◽  
Vol 4 (1-2) ◽  
pp. 41-45 ◽  
Author(s):  
Takeo Koshida ◽  
Sylvia Wu ◽  
Hitoshi Suzuki ◽  
Rimda Wanchoo ◽  
Vanesa Bijol ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Thrombotic Microangiopathy ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kidney Biopsy ◽  
Kinase Inhibitor ◽  
Target Effect

Dasatinib is the second-generation tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia. Proteinuria has been reported with this agent. We describe two kidney biopsy–proven cases of dasatinib-induced thrombotic microangiopathy that responded to stoppage of dasatinib and using an alternate tyrosine kinase inhibitor. Certain specific tyrosine kinase inhibitors lead to endothelial injury and renal-limited thrombotic microangiopathy. Hematologists and nephrologists need to be familiar with this off-target effect of dasatinib.

scholarly journals Handling challenging questions in the management of chronic myeloid leukemia: when is it safe to stop tyrosine kinase inhibitors?

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 243-247
Author(s):  
Delphine Rea
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Treatment Free Remission

Abstract The paradigm for managing patients with chronic myeloid leukemia is evolving. In the recent past, restoring a normal life expectancy while patients are receiving never-ending targeted therapy with BCR–ABL1 tyrosine kinase inhibitors through prevention of progression to blast phase and mitigation of iatrogenic risks was considered the best achievable outcome. Now, long-term treatment-free remission with continued response off tyrosine kinase inhibitor therapy is recognized as the most optimal benefit of treatment. Indeed, numerous independent clinical trials provided solid proof that tyrosine kinase inhibitor discontinuation was feasible in patients with deep and sustained molecular responses. This article discusses when tyrosine kinase inhibitors may be safely stopped in clinical practice on the basis of the best and latest available evidence.

scholarly journals Handling challenging questions in the management of chronic myeloid leukemia: when is it safe to stop tyrosine kinase inhibitors?

2020 ◽  
Vol 4 (21) ◽  
pp. 5589-5594
Author(s):  
Delphine Rea
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Treatment Free Remission

Abstract The paradigm for managing patients with chronic myeloid leukemia is evolving. In the recent past, restoring a normal life expectancy while patients are receiving never-ending targeted therapy with BCR–ABL1 tyrosine kinase inhibitors through prevention of progression to blast phase and mitigation of iatrogenic risks was considered the best achievable outcome. Now, long-term treatment-free remission with continued response off tyrosine kinase inhibitor therapy is recognized as the most optimal benefit of treatment. Indeed, numerous independent clinical trials provided solid proof that tyrosine kinase inhibitor discontinuation was feasible in patients with deep and sustained molecular responses. This article discusses when tyrosine kinase inhibitors may be safely stopped in clinical practice on the basis of the best and latest available evidence.

Aplastic anemia secondary to tyrosine kinase inhibitor therapy in a patient with chronic myeloid leukemia

2021 ◽  
pp. 107815522110520
Author(s):  
Olfa Kassar ◽  
Rahma Mallek ◽  
Fatma Ben Said ◽  
Faten Kallel ◽  
Kamilia Ksouda ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Aplastic Anemia ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Molecular Response ◽  
Fatty Tissue

Introduction Nilotinib, as the second generation of tyrosine kinase inhibitor, has significant efficacy in patients with chronic myeloid leukemia resistant or intolerant to Imatinib. Aplastic anemia induced by tyrosine kinase inhibitors is an uncommon complication. Case report A 34-year-old female case with CML in the chronic phase was treated with Imatinib in first-line therapy. Nilotinib was switched because of failure to achieve complete cytogenetic response at 6 months following Imatinib. Three years with Nilotinib, the patient developed a persistent pancytopenia grade 4 while a major molecular response was achieved. Management & Outcome Nilotinib was discontinued. However, the hematologic finding of the patient had not recovered after three months. A bone marrow biopsy showed marked hypocellularity and fatty tissue without evidence of myelofibrosis. Immunosuppressive therapy was started. Unfortunately, the patient died due to septic and hemorrhagic shock nine months after Nilotinib interruption. According to Naranjo's algorithm, the causality relationship with the drug is probable with a score of 5. Discussion Aplastic anemia is an uncommon adverse event of tyrosine kinase inhibitors but it can be a fatal complication. The early diagnosis of aplastic anemia related to Nilotinib therapy is needed to avoid further detrimental effects of the drug.

scholarly journals Krónikus myeloid leukaemia miatt 2003 és 2019 között a Semmelweis Egyetem Belgyógyászati és Onkológiai Klinikáján kezelt betegek adatainak elemzése

2021 ◽  
Vol 162 (32) ◽  
pp. 1297-1302
Author(s):  
Júlia Weisinger ◽  
Ilona Tárkányi ◽  
Eid Hanna ◽  
Ágnes Kárpáti ◽  
Zsolt Nagy ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukaemia ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Treatment Change

Összefoglaló. Bevezetés: A krónikus myeloid leukaemia a diagnosztika fejlődésének és a tirozin-kináz-gátlók bevezetésének köszönhetően az elmúlt évtizedekben kiváló prognózisú betegséggé vált. Célkitűzés: A betegséggel kapcsolatos ismereteink nagy része klinikai vizsgálatokból származik, emiatt kiemelt szerepük van a nem szelektált beteganyagon végzett elemzéseknek. Módszer: Retrospektív elemzésünkben a Semmelweis Egyetem Belgyógyászati és Onkológiai Klinikáján 2003 és 2019 között tirozin-kináz-gátló kezelésben részesült betegek adatait tekintettük át. Eredmények: Klinikánkon összesen 88 beteg részesült terápiában, közülük 73 beteg az analízis időpontjában is kezelés alatt állt. A betegek 5 éves össztúlélése 86%, 5 éves progressziómentes túlélése 70% volt. 9 beteg halt meg, közülük 2 betegnél a halál oka a progrediáló alapbetegség volt. 38 betegnél volt szükség az első vonalban terápiaváltásra, a váltás oka akkor elsősorban az elégtelen terápiás válasz volt. A későbbi terápiaváltásokra elsősorban intolerancia miatt került sor. Az első vonalban a betegek több mint fele major molekuláris választ ért el, a jelenlegi kezelés mellett a betegek 85%-ánál major molekuláris választ detektáltunk. Megbeszélés: Adataink alapján az intézményünkben kezelt betegek túlélése és a betegek által elért terápiás válasz megfelel a nemzetközi adatoknak. Következtetés: Mivel nem válogatott beteganyagról van szó, a kapott eredmények pontosabb képet adhatnak a krónikus myeloid leukaemia tirozin-kináz-gátlóval történt kezelésének eredményeiről. Orv Hetil. 2021; 162(32): 1297–1302. Summary. Introduction: As a result of advances in diagnostic techniques and the introduction of tyrosine kinase inhibitors, the prognosis of chronic myeloid leukemia has improved over the last decades. Objective: Most of our knowledge about chronic myeloid leukemia results from clinical trials, therefore data derived from non-selected patient population is substantial. Method: Data of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors at the Department of Internal Medicine and Oncology, Semmelweis University, between 2003 and 2019 were analysed retrospectively. Results: 88 patients received treatment, 73 patients were on therapy at the time of the analysis. Overall survival at 5 years was 86%, progression-free survival at 5 years was 70%. 9 patients died, 2 of them due to progressive disease. 38 patients needed 2nd line therapy, the main reason of treatment change was failure of therapy. Subsequent treatment modifications were conducted mostly because of intolerance. More than half of the patients on 1st line treatment reached major molecular response and 85% of the patients on treatment at the end of the analysis are in major molecular response. Discussion: Based on our data, survival and therapeutic response of patients in our center are similar to the international results. Conclusion: This analysis provides real-world data about treatment results of chronic myeloid leukemia in the tyrosine kinase inhibitor era. Orv Hetil. 2021; 162(32): 1297–1302.

scholarly journals Use of tyrosine kinase inhibitor by patients with chronic myeloid leukemia at a public hematology institution in the state of Amazonas, Brazil

2020 ◽  
Vol 11 (4) ◽  
pp. 510
Author(s):  
Andreia D. MENEZES ◽  
Nelson A. FRAIJI
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Cross Sectional Study ◽  
Chi Square ◽  
Cross Sectional ◽  
The Right

Objectives: To evaluate the conditions of use of tyrosine kinase inhibitors and adherence by patients with chronic myeloid leukemia treated at a public hematology institution. Methods: This was an observational and cross-sectional study carried out from December 2015 to April 2016. Data collection was carried out through interviews with standardized questionnaires that assessed the socioeconomic and demographic profile, drug therapy and by the Morisky-Green test that assessed the green adherence. Patients over 18 years old who had been using one of the tyrosine kinase inhibitors for more than one month were included; imatinib, dasatinib or nilotinib and who signed the informed consert form, agreement to participate in study. Descriptive statistical analysis and chi-square test with Yates correction were performed. Results: 63 patients were interviewed, with a mean age of 50 years with a standard deviation of 15.95. being 60% men. As for knowledge about the aspects related to the use of inhibitors: 95.2% took at the right time, 93.7% did not use other medications concomitantly, 63.5% kept it in an appropriate place and 97% of the patients received prior guidance from the doctor about the use. As for information about treatment, 90.5% knew the purpose of taking the medication, 60% did not know the time of use, 83% did not know what would happen if they stopped taking it and 73% believed they could stop the treatment at some point. Adherence to treatment was identified 46% of patients. Conclusion: No statistically significant differences were found between having or not adherence, when compared with the studied variables.

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.

Cardiac birth defects in a twin infant born to a woman with chronic myeloid leukemia on dasatinib

2017 ◽  
Vol 25 (3) ◽  
pp. 699-702 ◽  
Author(s):  
David J Hermel ◽  
Victor Chiu ◽  
Melody H Hermel ◽  
Anil Tulpule ◽  
Mojtaba Akhtari
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Twin Pregnancy ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Case Series ◽  
Normal Pregnancy ◽  
Low Birth Weight Infants

Preclinical animal studies have demonstrated an association between maternal use of tyrosine kinase inhibitors and embryofetal toxicity; yet, multiple clinical case series have reported normal pregnancy outcomes and healthy infants in women on these medications during the course of their pregnancy. We describe a case of a woman with chronic myeloid leukemia who had taken the second-generation tyrosine kinase inhibitor dasatinib during the first 12 weeks of her dichorionic diamniotic twin pregnancy and subsequently delivered two low-birth weight infants, one with severe cardiac malformations and the other without apparent birth abnormalities. To our knowledge, this is the first reported case of fetal cardiovascular defects in an infant born to a woman on dasatinib during a twin pregnancy and supports current recommendations to avoid this medication during pregnancy. We also review relevant preclinical and clinical studies of tyrosine kinase inhibitor use during pregnancy and explore alternative therapeutic options for patients with chronic myeloid leukemia during pregnancy to aid clinicians in the appropriate management of these patients so as to minimize both maternal and fetal risks.

scholarly journals Imatinib-Induced Keratosis Pilaris in a Patient with Chronic Myeloid Leukemia

2020 ◽  
Vol 3 (3) ◽  
pp. 221-224
Author(s):  
Maruma F
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Imatinib Mesylate ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Skin Lesions ◽  
Histological Evaluation ◽  
First Line Therapy

We discuss the case of a 23 years old female with chronic myeloid leukemia. This patient developed keratosis pilaris nearly three months after she was treated with imatinib mesylate for her chronic myeloid leukemia. She was then referred to our dermatology outpatient clinic for assessment of the skin lesions. Prior to initiating the tyrosinase kinase inhibitor, the patient had no skin lesions at all. The skin lesions were widespread and diffuse in distribution and featured a primary morphology of follicular keratotic papules. This clinical picture was in keeping with keratosis pilaris. The further histological evaluation also confirmed features compatible with this diagnosis. The tyrosine kinase inhibitors are considered first-line therapy for the treatment of chronic myeloid leukemia. Imatinib mesylate belongs to the first generation of oral tyrosine kinase inhibitors and has a long-term control on the chronic myeloid leukemia and good safety profile. Most cases of keratosis pilaris are reported to arise from the second generation of tyrosine kinase inhibitors such as Nilotinib. We report a case of keratosis pilaris associated with imatinib mesylate in a patient with chronic myeloid leukemia.

BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2843-2853 ◽  
Author(s):  
Mhairi Copland ◽  
Francesca Pellicano ◽  
Linda Richmond ◽  
Elaine K. Allan ◽  
Ashley Hamilton ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Progenitor Cells ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Hematopoietic Stem

Chronic myeloid leukemia (CML), a hematopoietic stem-cell disorder, cannot be eradicated by conventional chemotherapy or the tyrosine kinase inhibitor imatinib mesylate (IM). To target CML stem/progenitor cells, we investigated BMS-214662, a cytotoxic farnesyltransferase inhibitor, previously reported to kill nonproliferating tumor cells. IM or dasatinib alone reversibly arrested proliferation of CML stem/progenitor cells without inducing apoptosis. In contrast, BMS-214662, alone or in combination with IM or dasatinib, potently induced apoptosis of both proliferating and quiescent CML stem/progenitor cells with less than 1% recovery of Philadelphia-positive long-term culture-initiating cells. Normal stem/progenitor cells were relatively spared by BMS-214662, suggesting selectivity for leukemic stem/progenitor cells. The ability to induce selective apoptosis of leukemic stem/progenitor cells was unique to BMS-214662 and not seen with a structurally similar agent BMS-225975. BMS-214662 was cytotoxic against CML blast crisis stem/progenitor cells, particularly in combination with a tyrosine kinase inhibitor and equally effective in cell lines harboring wild-type vs mutant BCR-ABL, including the T315I mutation. This is the first report of an agent with activity in resistant and blast crisis CML that selectively kills CML stem/progenitor cells through apoptosis and offers potential for eradication of chronic phase CML.

scholarly journals Role of anti-apoptotic pathways activated by BCR/ABL in the resistance of chronic myeloid leukemia cells to tyrosine kinase inhibitors.

2013 ◽  
Vol 60 (4) ◽  
Author(s):  
Katarzyna Danisz ◽  
Janusz Blasiak
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Chronic Phase

Chronic myeloid leukemia (CML) is a hematological stem cell disorder characterized by the excessive proliferation of the myeloid lineage. In its initial chronic phase, the myeloid progenitor cells expand and demonstrate apparently normal differentiation. The disease may then transform into the accelerated phase, usually associated with resistance to therapy, and finally, into acute leukemic progression phase - blast crisis. Abnormal myeloid cells produce progenitors, which have lost their ability to differentiate, but retain the capacity to proliferate. The molecular hallmark of CML is the Philadelphia chromosome, resulting from reciprocal chromosome translocation, t(9;22)(q34;q11), and containing the BCR/ABL fusion gene, producing the BCR/ABL protein with a constitutive tyrosine kinase activity. BCR/ABL-positive cells have faster growth and proliferation over their normal counterparts and are resistant to apoptosis. Introduction of imatinib (IM), a tyrosine kinase inhibitor, revolutionized the therapy of CML, changing it from a fatal disease into a chronic disorder. However, some patients show a primary resistance to IM, others acquire such resistance in the course of therapy. Therefore, a small number of leukemic stem cells retains self-renewal capacity under IM treatment. Because BCR/ABL is involved in many signaling pathways, some of them may be essential for resistance to IM-induced apoptosis. The PI3K/AKT, Ras and JAK/STAT signaling pathways are involved in resistance to apoptosis and can be activated by BCR/ABL. Therefore, they can be candidates for BCR/ABL-dependent pro-survival pathway(s), allowing a fraction of CML cells to withstand treatment with tyrosine kinase inhibitors.

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