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1. P708: CANADIAN AND RUSSIAN EXPERIENCES OF ASCIMINIB IN CHRONIC MYELOID LEUKEMIA (CML) PATIENTS WHO FAILED MULTIPLE LINES OF TYROSINE KINASE INHIBITOR (TKI) THERAPY.

Author

F. Khadadah, A. G. Turkina, E. Lomaia, E. V. Morozova, O. A. Shukhov, A. Petrova, T. Chitanava, J. J. Vlasova, E. Kuzmina, I. Nemchenko, E. Y. Chelysheva, A. Bykova, M. Gurianova, A. Xenocostas, L. Busque, K. Jamani, S. Cerquozzi, P. Kuruvilla, R. Kaedbey, B. Leber, S. Assouline, and D. D. H. Kim

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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3. Exome, transcriptome and miRNA analysis don’t reveal any molecular markers of TKI efficacy in primary CML patients

Author

Ekaterina Chelysheva, Elmira P. Adilgereeva, Oleg Shukhov, Alexander Lavrov, Grigory Tsaur, Sergey V. Mordanov, Sergey I. Kutsev, Konstantin S. Kochergin-Nikitsky, Valentina D Yakushina, Anna G. Turkina, and S. A. Smirnikhina

Subjects
0301 basic medicine, Oncology, Male, miRNA analysis, Transcriptome, 0302 clinical medicine, hemic and lymphatic diseases, Exome, Genetics (clinical), Chronic myeloid leukemia, Myeloid leukemia, Middle Aged, Prognosis, Treatment Outcome, 030220 oncology & carcinogenesis, Imatinib Mesylate, Female, DNA microarray, medicine.drug, Adult, medicine.medical_specialty, lcsh:Internal medicine, Genotype, lcsh:QH426-470, 03 medical and health sciences, Young Adult, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, microRNA, Genetics, medicine, Biomarkers, Tumor, Humans, TKI efficacy, lcsh:RC31-1245, Genotyping, Protein Kinase Inhibitors, Aged, Polymorphism, Genetic, business.industry, Research, Imatinib, respiratory tract diseases, Gene expression profiling, MicroRNAs, lcsh:Genetics, 030104 developmental biology, business
Abstract

Background Approximately 5–20% of chronic myeloid leukemia (CML) patients demonstrate primary resistance or intolerance to imatinib. None of the existing predictive scores gives a good prognosis of TKI efficacy. Gene polymorphisms, expression and microRNAs are known to be involved in the pathogenesis of TKI resistance in CML. The aim of our study is to find new molecular markers of TKI therapy efficacy in CML patients. Methods Newly diagnosed patients with Ph+ CML in chronic phase were included in this study. Optimal and non-optimal responses to TKI were estimated according to ELN 2013 recommendation. We performed genotyping of selected polymorphisms in 62 blood samples of CML patients, expression profiling of 33 RNA samples extracted from blood and miRNA profiling of 800 miRNA in 12 blood samples of CML patients. Results The frequencies of genotypes at the studied loci did not differ between groups of patients with an optimal and non-optimal response to TKI therapy. Analysis of the expression of 34,681 genes revealed 26 differently expressed genes (p

Published
2019
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4. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia : a randomized, open-label phase 2 clinical trial

Author

James K. McCloskey, Andreas Hochhaus, Lori J. Maness, Michael W. Deininger, Vickie Lu, Tomasz Sacha, Christine Rojas, Charles Chuah, Moshe Talpaz, Beatriz Moiraghi, Tracey Hall, Anna G. Turkina, Jorge E. Cortes, Maria Undurraga Sutton, Hugues de Lavallade, Gianantonio Rosti, Christopher Arthur, Elza Lomaia, Michael J. Mauro, Charles A. Schiffer, Shouryadeep Srivastava, Jane F. Apperley, Carolina Pavlovsky, Jeffrey H. Lipton, Philippe Rousselot, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier de Versailles André Mignot (CHV), Bristol-Myers Squibb, BMS, Pfizer, Astellas Pharma US, APUS, Novartis, Takeda Pharmaceuticals U.S.A., TPUSA, Jazz Pharmaceuticals, Daiichi-Sankyo, Sun Pharma, Conflict-of-interest disclosure: J.C. has been a consultant to and received research funding from Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, and BioPath Holdings, has received research funding from Sun Pharma, Telios, Arog, Merus, and Immunogen, has held membership on the board of directors or advisory committee of BioPath Holdings, and has been a consultant to Amphivena Therapeutics and BiolineRx. J.A. has received honoraria and research funding and is on the speakers bureaus of Incyte and Pfizer, and has received honoraria and served on the speakers bureaus of Bristol Myers Squibb and Novartis. E.L. has served on the speakers bureaus of Novartis and Pfizer, and has received travel and accommodation reimbursement from Novartis, Pfizer, and Bristol Myers Squibb. B.M. has served on the speakers bureaus of Novartis, Pfizer, and Takeda. M.U.S. has served on the advisory boards of AbbVie, Janssen, Novartis, Pfizer, and Roche and on the speakers bureaus of Janssen, Novartis, and Pfizer. C.C. has received honoraria from Novartis and Korea Otsuka Pharmaceutical, received honoraria and research funding from Bristol Myers Squibb, and received travel reimbursement and research funding from Pfizer. T.S. has been a consultant to, has received honoraria from, and has served on the speakers bureaus of Bristol Myers Squibb, Novartis, Pfizer, and Incyte, and has been a consultant to and received honoraria from Adamed. J.H.L. has been a consultant to and has received research funding from Bristol Myers Squibb, Ariad, Pfizer, and Novartis. C.A.S. has been a consultant to Bristol Myers Squibb and Novartis, and has received research funding from Takeda. A.H. has received honoraria and research funding from Bristol Myers Squibb, Novartis, and Pfizer, research funding from Incyte and Merck Sharp & Dohme, and honoraria from Takeda. P.R. has been a consultant to and has received funding from Incyte and Pfizer, and has been a consultant to Bristol Myers Squibb, Novartis, and Takeda. G.R. has received research funding from and served on the speakers bureau for Pfizer, and has served on the speakers bureaus of Bristol Myers Squibb, Incyte, and Novartis. H. de L. has received honoraria and research funding from Bristol Myers Squibb and Incyte, and honoraria from Pfizer and Novartis. C.R. has received personal fees from AstraZeneca, Roche, Novartis, and Janssen. M.T. holds membership on the board of directors or advisory committees of Bristol Myers Squibb and Constellation Pharmaceuticals, has received research funding from Takeda and Novartis, and has been a consultant to IMAGO. M.M. has been a consultant to and has received honoraria, reimbursement of travel, accommodation and expenses, and research funding from Bristol Myers Squibb, Novartis, Takeda, and Pfizer, and research funding from Sun Pharma/SPARC. T.H. and V.L. are employees of Millennium Pharmaceuticals. S.S. is an employee of Takeda. M.D. is a consultant to, holds a membership on the board of directors or advisory committees of, was part of a study management committee of, and received research funding from Blueprint Medicines Corporation, is a consultant to Fusion Pharma, Medscape, and DisperSol, is a consultant to, has held membership on the board of directors or advisory committees of, and has received research funding from Takeda, is a consultant to and holds membership on the board of directors or advisory committee of Sangamo, is a consultant to and received research funding from Novartis, is a consultant to and received honoraria and research funding from Incyte, and has received research funding from SPARC, DisperSol, and the Leukemia and Lymphoma Society. C.P., A.T., C.K.A., J. M., and L.M. declare no competing financial interests., and Professional medical writing assistance was provided by Duprane Young of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by Millennium Pharmaceuticals, Inc.

Subjects
Adult, Male, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Population, Fusion Proteins, bcr-abl, Phases of clinical research, Antineoplastic Agents, Biochemistry, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Clinical endpoint, Humans, Prospective cohort study, education, Protein Kinase Inhibitors, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, education.field_of_study, Dose-Response Relationship, Drug, business.industry, Ponatinib, Imidazoles, Cell Biology, Hematology, Middle Aged, Dose-ranging study, 3. Good health, Pyridazines, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Relative risk, Leukemia, Myeloid, Chronic-Phase, Cohort, Female, business
Abstract

In PACE (Ponatinib Ph+ ALL and CML Evaluation), a phase 2 trial of ponatinib that included patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to multiple prior tyrosine kinase inhibitors (TKIs), ponatinib showed deep and durable responses, but arterial occlusive events (AOEs) emerged as notable adverse events. Post hoc analyses indicated that AOEs are dose dependent. We assessed the benefit/risk ratio across 3 ponatinib starting doses in the first prospective study to evaluate a novel, response-based, dose-reduction strategy for TKI treatment. Adults with CP-CML resistant to or intolerant of at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1 T315I mutation were randomly assigned 1:1:1 to 3 cohorts receiving ponatinib 45, 30, or 15 mg once daily. In patients who received 45 or 30 mg daily the dose was reduced to 15 mg upon response (BCR-ABL1IS transcript levels ≤1%). The primary end point was response at 12 months. From August 2015 through May 2019, 283 patients were randomly assigned to the cohorts: 282 (94 per dose group) received treatment (data cutoff, 31 May 2020). The primary end point (98.3% confidence interval) was achieved in 44.1% (31.7-57.0) in the 45-mg cohort, 29.0% (18.4-41.6) in the 30-mg cohort, and 23.1% (13.4-35.3) in the 15-mg cohort. Independently confirmed grade 3 or above treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 45-, 30-, and 15-mg cohorts, respectively. All cohorts showed benefit in this highly resistant CP-CML population. Optimal benefit/risk outcomes occurred with the 45-mg starting dose, which was decreased to 15 mg upon achievement of a response. This trial is registered on www.clinicaltrials.gov as NCT02467270.

Published
2021
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5. TARGET: a survey of real-world management of chronic myeloid leukaemia across 33 countries

Author

Timothy P. Hughes, Anna G. Turkina, Solenn Le Clanche, Hani Al Hashmi, Güray Saydam, Chul Won Jung, Vikram Mathews, Mohamed A. Yassin, Darko Miljkovic, Jianxiang Wang, Cassandra Slader, and Ege Üniversitesi

Subjects
Male, medicine.medical_specialty, media_common.quotation_subject, Steering committee, Physician education, Chronic myeloid leukaemia, 03 medical and health sciences, 0302 clinical medicine, chronic myeloid leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Surveys and Questionnaires, hemic and lymphatic diseases, tyrosine kinase inhibitors, medicine, Humans, Quality (business), media_common, Government, treatment-free remission, business.industry, Hematology, Treatment efficacy, Work (electrical), 030220 oncology & carcinogenesis, Family medicine, real-life practice, Practice Guidelines as Topic, Female, Primary treatment, business, management, 030215 immunology
Abstract

Despite the availability of guidelines for the management of chronic myeloid leukaemia (CML), various issues may prevent their successful implementation. the TARGET survey examined real-world management of CML patients compared with international recommendations. This online survey was completed in 2017. Results were discussed by a Steering Committee (SC) of eight international haematologists, challenges were identified and practical solutions developed. of the 1008 haematologists invited (33 countries), 614 completed the survey. Gaps regarding treatment efficacy and molecular monitoring were identified. Half of the physicians did not perform three-monthly testing of during the initial 12 months of treatment, citing cost as the major barrier, although they know it should be done. Treatment-free remission was not considered a primary treatment goal or as a priority factor influencing treatment decisions. European Leukemia Net guidelines interpretation was generally acceptable, but awareness regarding management of persistent adverse events was poor. Practical solutions proposed by the SC were mostly focused on enhancing physician education and awareness, or encouraging hospitals to work with the government, in order to improve the quality of BCR-ABL testing. Gaps in current CML management were identified compared with international recommendations, which the proposed practical solutions would help to address., NovartisNovartis, This study was funded by Novartis and set up by KPL. Medical writing assistance with the preparation of this manuscript was provided by KPL and Galien Health Publishing, with funding provided by Novartis.

Published
2020

6. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

Author

Simona Soverini, Jeffrey H. Lipton, Richard A. Larson, Dietger Niederwieser, Andrey Zaritskey, Fabrizio Pane, Francois-Xavier Mahon, Jeroen Janssen, Richard E. Clark, François Guilhot, Juan Luis Steegmann, Jerald P. Radich, Michael W. Deininger, Andreas Hochhaus, Richard T. Silver, Susanne Saußele, Johan Richter, Timothy P. Hughes, Jane F. Apperley, Jiří Mayer, Henrik Hjorth-Hansen, Hagop M. Kantarjian, Jorge E. Cortes, Anna G. Turkina, Michele Baccarani, Gianantonio Rosti, Franck E. Nicolini, Philippe Rousselot, Giuseppe Saglio, Delphine Rea, Dong-Wook Kim, Ruediger Hehlmann, Charles A. Schiffer, Francisco Cervantes, Hochhaus A., Baccarani M., Silver R.T., Schiffer C., Apperley J.F., Cervantes F., Clark R.E., Cortes J.E., Deininger M.W., Guilhot F., Hjorth-Hansen H., Hughes T.P., Janssen J.J.W.M., Kantarjian H.M., Kim D.W., Larson R.A., Lipton J.H., Mahon F.X., Mayer J., Nicolini F., Niederwieser D., Pane F., Radich J.P., Rea D., Richter J., Rosti G., Rousselot P., Saglio G., Saussele S., Soverini S., Steegmann J.L., Turkina A., Zaritskey A., Hehlmann R., Hochhaus, A., Baccarani, M., Silver, R. T., Schiffer, C., Apperley, J. F., Cervantes, F., Clark, R. E., Cortes, J. E., Deininger, M. W., Guilhot, F., Hjorth-Hansen, H., Hughes, T. P., Janssen, J. J. W. M., Kantarjian, H. M., Kim, D. W., Larson, R. A., Lipton, J. H., Mahon, F. X., Mayer, J., Nicolini, F., Niederwieser, D., Pane, F., Radich, J. P., Rea, D., Richter, J., Rosti, G., Rousselot, P., Saglio, G., Saussele, S., Soverini, S., Steegmann, J. L., Turkina, A., Zaritskey, A., Hehlmann, R., Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Bergonié [Bordeaux], UNICANCER, Centre Léon Bérard [Lyon], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Novartis Berlin Mathematical School, BMS Daiichi-Sankyo Janssen Pharmaceuticals Angelini Pharma Pfizer, The ELN panel for recommendations in CML comprises 34 experts from Europe, America, and the Asian-Pacific areas. The panel met six times at international meetings of the American Society of Hematology (2015, 2016), the European School of Hematology (2017), the ELN (2019), the European Investigators on CML (2019), and the European School of Hematology/International CML Foundation (2019). Five sets of key questions were submitted to panel members to complement the meetings. Discordant opinions were harmonized by email discussions, and a consensus of 75–100% was reached in most, but not all instances. Unresolved controversies are described in the discussion section. The costs of the meetings and the preparation of the interim and final reports were born entirely by ELN, a research network of excellence initiated by the European Union, now funded by donations and projects of ELN participants. There was no financial support from industry for any activity. Treatment recommendations are limited to the TKIs that have been approved with at least one indication in CML, either by the US Federal Drug Administration (FDA) or/and by the European Medicine Agency (EMA). The drugs are listed in the order of FDA approval. The panel acknowledges that not all drugs may be available worldwide and that the high price of some makes access to these drugs problematic in some countries., Conflict of interest Members of the expert panel declare the following potential conflicts of interest: AH, Research support: Novartis, BMS, MSD, Pfizer, Incyte. Honoraria: Novartis, BMS, Pfizer, Incyte, Takeda, Fusion Pharma. MB, Honoraria: Novartis, BMS, Pfizer, Incyte, Ariad, Takeda, Fusion Pharma. Logistic support: Novartis, BMS, Pfizer, Incyte, Ariad. CS, Research support: Ariad. Honoraria: Novartis, Teva, Pfizer, Juno, Astellas, Ambit. JFA, Research support: Incyte, Novartis, Pfizer. Honoraria: Incyte, Novartis, Pfizer, BMS. FC, Honoraria: Novartis, BMS, Pfizer, Incyte, Celgene, Italfarmaco. Travel grants: BMS, Celgene. REC, Research support: Novartis, Pfizer, BMS. Honoraria: Novartis, Pfizer, BMS, Ariad/Incyte, Jazz, Abbvie. JEC, Research support: BMS, Novartis, Pfizer, Sun Pharma, Takeda. Honoraria: Novartis, Pfizer, Takeda. MWD, Research support: Takeda, Novartis, Pfizer, Incyte, SPARC, TetraLogic Pharmaceuticals, Blueprint. Honoraria: Blueprint, Fusion Pharma, Novartis, Sangamo, Ascentage Pharma, Adelphi, CTI, BMS, Pfizer, Takeda, Medscape, Incyte, Humana, TRM, Ariad, Galena Biopharma. FG, Research support: Novartis, Roche. Honoraria: Novartis, BMS, Celgene. HHH, Research support: Pfizer, BMS, Merck, Austrian Orphan Pharma, Nordic Cancer Union. Honoraria: Pfizer, Incyte, Austrian Orphan Pharma. TPH, Research support: Novartis, BMS, Celgene. Honoraria: Novartis, BMS, Fusion Pharma. Travel grants: Novartis. JJ, Research support: Novartis, BMS. President, Apps for Care and Science, nonprofit foundation supported by Daiichi-Sankyo, Janssen, Incyte, BMS, Servier, Jazz, Celgene. Honoraria: Abbvie, Novartis, Pfizer, Incyte. HMK, Research support: AbbVie, Agios, Amgen, Ariad, Astex, BMS, Cyclacel, Daiichi-Sankyo, Immunogen, Jazz Pharma, Novartis, Pfizer. Honoraria: AbbVie, Actinium, Agios, Amgen, Immunogen, Pfizer, Takeda. DWK, Research support: Novartis, Pfizer, BMS, Takeda, Il-Yang Co. Honoraria: Novartis, BMS, Otsuka, Il-Yang Co. RAL, Research support: Astellas, Celgene, Cellectis, Daiichi Sankyo, Novartis, Rafael Pharmaceuticals. Honoraria: Amgen, Celgene, CVS Caremark, Epizyme, Novartis, Takeda. JHL, Research support and honoraria: Novartis, BMS, Pfizer, Takeda. FXM, Research support and honoraria: Novartis. Travel grants: Celgene, Pfizer, Astra Zeneca. JM, Research support: Angelini, Pfizer, Novartis, BMS. Travel grants: Novartis. FN, Research support: Novartis, Incyte. Honoraria: Incyte biosciences, Novartis, BMS, Sun Pharma. Travel grants: Incyte biosciences, Novartis, BMS. DN, Research support: Daiichi, Honoraria: Cellectis. Travel grants: EUSA, Novartis, and Amgen. FP, Research support: Novartis. Honoraria: Novartis, BMS, Pfizer, Incyte. JPR, Research support: Novartis. Honoraria: Novartis, BMS, Ariad, Amgen, Takeda, Cepheid, Bio-Rad, Adaptive, Seagen, Gilead. DR, Honoraria: BMS, Novartis, Pfizer, Incyte. JR, Honoraria: Novartis, Pfizer. GR, Research support, honoraria, and travel grants: Novartis, BMS, Incyte, Pfizer, Roche. PR, Research support: Incyte, Pfizer. Honoraria: BMS, Incyte, Pfizer, Novartis. GS, Honoraria: Novartis, BMS, Incyte, Pfizer. SiS, Honoraria: Incyte. SuS, Research support: BMS, Incyte, Novartis. Honoraria: BMS, Incyte, Novartis, Pfizer. Travel grants: BMS, Incyte, Novartis. JLS, Research support, honoraria, and travel grants: BMS, Incyte, Novartis, Pfizer. AT, Honoraria: BMS, Novartis, Pfizer, Fusion Pharma. Travel grants: BMS, Novartis, Pfizer. AZ, Research support: Novartis, Celgene, Janssen. Travel grants: Novartis. RTS, RH, none.

Subjects
Oncology, Cancer Research, Consensus Development Conferences as Topic, Dasatinib, Fusion Proteins, bcr-abl, Quinoline, Gene Expression, Review Article, Tyrosine-kinase inhibitor, Antineoplastic Agent, European LeukemiaNet, 0302 clinical medicine, hemic and lymphatic diseases, 0303 health sciences, Aniline Compounds, Myeloid leukemia, Disease Management, Hematology, Aniline Compound, 3. Good health, 030220 oncology & carcinogenesis, Quinolines, Imatinib Mesylate, Bosutinib, Nitrile, medicine.drug, Human, medicine.medical_specialty, medicine.drug_class, Clinical Decision-Making, Protein Kinase Inhibitor, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Targeted therapies, Life Expectancy, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Nitriles, medicine, Humans, Protein Kinase Inhibitors, Chronic myeloid leukaemia, 030304 developmental biology, Monitoring, Physiologic, business.industry, Imatinib, Survival Analysis, Discontinuation, Pyrimidines, Nilotinib, Pyrimidine, Quality of Life, business
Abstract

The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.

Published
2020
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7. Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin

Author

Michele Baccarani, Joerg Hasford, Anna G. Turkina, Michael Lauseker, Elza Lomaia, Laimonas Griskevicius, Joelle Guilhot, Verena S. Hoffmann, Andreas Hochhaus, Gert J. Ossenkoppele, Perttu Koskenvesa, Daniela Zackova, Markus Pfirrmann, Sonja Heibl, Ulla Olsson-Strömberg, Andrija Bogdanovic, Edgar Faber, Gabriele Schubert-Fritschle, Richard E. Clark, Witold Prejzner, Katharina Bachl, Tomasz Sacha, HUS Comprehensive Cancer Center, Department of Oncology, Hematologian yksikkö, University of Helsinki, Hematology, and CCA - Cancer Treatment and quality of life

Subjects
Oncology, Male, Myeloid, Cell Count, WORLD-HEALTH-ORGANIZATION, Kaplan-Meier Estimate, Blast Count, RECOMMENDATIONS, Hemoglobins, 0302 clinical medicine, Bone Marrow, hemic and lymphatic diseases, Registries, Aged, 80 and over, Hematology, CHRONIC MYELOGENOUS LEUKEMIA, Age Factors, Myeloid leukemia, Middle Aged, Prognosis, 3. Good health, ERA, Europe, Leukemia, medicine.anatomical_structure, 030220 oncology & carcinogenesis, SURVIVAL, Neoplastic Stem Cells, Female, chronic myeloid leukemia, advanced phase, registry, prognosis, medicine.drug, Adult, medicine.medical_specialty, 2904 CML PATIENTS, Adolescent, 3122 Cancers, Leukemia, Myeloid, Accelerated Phase, IMATINIB, 03 medical and health sciences, Young Adult, Internal medicine, medicine, TYROSINE KINASE INHIBITORS, MANAGEMENT, Humans, Hematologi, Aged, Neoplasm Staging, Proportional Hazards Models, Chromosome Aberrations, Proportional hazards model, business.industry, Imatinib, medicine.disease, RANDOMIZED CML, business, Blast Crisis, 030215 immunology, Chronic myelogenous leukemia, Follow-Up Studies
Abstract

Chronic myeloid leukemia (CML) is usually diagnosed in chronic phase, yet there is a small percentage of patients that is diagnosed in accelerated phase or blast crisis. Due to this rarity, little is known on the prognosis of these patients. Our aim was to identify prognostic factors for this cohort. We identified 283 patients in the EUTOS population-based and out-study registries that were diagnosed in advanced phase. Nearly all patients were treated with tyrosine kinase inhibitors. Median survival in this heterogeneous cohort was 8.2 years. When comparing patients with more than 30% blasts to those with 20-29% the hazard ratio (HR) was 1.32 (95%-confidence interval (CI): [0.7 - 2.6]). Patients with 20-29% had a significantly higher risk than patients with less than 20% blasts (HR: 2.24, 95%-CI: [1.2 - 4.0], p = 0.008). We found that the blast count was the most important prognostic factor; however, age, hemoglobin, basophils and other chromosomal aberrations should be considered as well. The ELTS score was able to define two groups (high risk vs. non-high risk) with an HR of 3.01 (95%-CI: [1.81 - 5.00], p

Published
2019
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8. Breastfeeding in patients with chronic myeloid leukaemia: case series with measurements of drug concentrations in maternal milk and review of literature

Author

Roman G. Shmakov, Sergey Aleshin, Ekaterina Chelysheva, Igor Shokhin, Anna G. Turkina, Evgenia Polushkina, and Ghermes G. Chilov

Subjects
Drug, medicine.medical_specialty, media_common.quotation_subject, chronic myeloid leukaemia, pregnancy, breastfeeding, milk, breast milk, imatinib, nilotinib, dasatinib, molecular response, Cmax, Breastfeeding, Breast milk, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, media_common, Pregnancy, business.industry, lcsh:RC633-647.5, Imatinib, Hematology, lcsh:Diseases of the blood and blood-forming organs, medicine.disease, Dasatinib, Infectious Diseases, Nilotinib, 030220 oncology & carcinogenesis, business, 030215 immunology, medicine.drug
Abstract

Breastfeeding in patients with chronic myeloid leukaemia (CML) who take tyrosine kinase inhibitors (TKIs) is not recommended but interruption of TKI treatment may cause the loss of remission. We observed the kinetics of the leukaemic clone in 3 women with CML in accordance with treatment interruptions for pregnancy and breastfeeding. The concentrations of nilotinib and imatinib in maternal milk were measured when the breastfeeding period was over. Nilotinib transfer into human breast milk was demonstrated for the first time and had a maximum concentration (Cmax) 129 ng/ml after 4 hours of the drug intake at a dose of 400 mg. The Cmax of imatinib in maternal milk ranged from 420 to 1411 ng/ml after 4-8 hours of the drug intake at a dose of 400-600 mg. Breastfeeding without TKI treatment may be safe with molecular monitoring, but preferably in those patients with CML who have durable deep molecular response.

Published
2018

9. Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase : results From a Single-Group, Phase 2, Open-Label Study

Author

Raquel De Paz, Carla Boquimpani, Sandip Acharya, Sikander Ailawadhi, Stephane Wong, Noam Benyamini, Franck E. Nicolini, Nelma Cristina D. Clementino, Jolanta Dengler, Rafik Fellague-Chebra, Dong-Wook Kim, Tomasz Sacha, Vasily Shuvaev, Yu Jin, Beatriz Moiraghi, Timothy P. Hughes, Jeffrey H. Lipton, Anna G. Turkina, Naoto Takahashi, and François Xavier Mahon

Subjects
medicine.medical_specialty, medicine.drug_class, business.industry, Myeloid leukemia, Imatinib, General Medicine, medicine.disease, Tyrosine-kinase inhibitor, Discontinuation, 03 medical and health sciences, Leukemia, 0302 clinical medicine, Imatinib mesylate, Nilotinib, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Internal medicine, Internal Medicine, medicine, Clinical endpoint, business, 030215 immunology, medicine.drug
Abstract

Background Treatment-free remission (TFR)-that is, stopping tyrosine kinase inhibitor (TKI) therapy without loss of response-is an emerging treatment goal in chronic myeloid leukemia (CML). Objective To evaluate TFR after discontinuation of second-line nilotinib therapy. Design Single-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905). Setting 63 centers in 18 countries. Patients Adults with CML in chronic phase who received TKI therapy for at least 3 years (>4 weeks with imatinib, then ≥2 years with nilotinib) and achieved MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1IS]) while receiving nilotinib entered a 1-year consolidation phase. Those with sustained MR4.5 during consolidation were eligible to enter TFR. Interventions Patients received nilotinib during consolidation; those who entered TFR stopped treatment. Patients with loss of major molecular response (MMR) (BCR-ABL1IS ≤0.1%) or confirmed loss of MR4 (BCR-ABL1IS ≤0.01%) during TFR reinitiated nilotinib treatment. Measurements Proportion of patients without loss of MMR, confirmed loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment (primary end point). Results 163 patients who had switched from imatinib to nilotinib (for reasons including resistance, intolerance, and physician preference) enrolled in the study and entered the consolidation phase. Of these patients, 126 met the criteria for entering the TFR phase, and 73 (58% [95% CI, 49% to 67%]) and 67 (53% [CI, 44% to 62%]) maintained TFR at 48 weeks (primary end point) and 96 weeks, respectively. Of the 56 patients who reinitiated nilotinib therapy, 55 regained MMR or better and 52 regained MR4.5. None had CML progression to accelerated phase or blast crisis. Musculoskeletal pain was more frequent during the first 48 weeks after nilotinib discontinuation. Limitation The study included a heterogeneous patient population and was not designed to compare outcomes between patients continuing and those stopping treatment. Conclusion TFR seems achievable in patients with sustained MR4.5 after switching to nilotinib. Primary funding source Novartis Pharmaceuticals Corporation.

Published
2018

10. Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia

Author

Sergey I. Kutsev, Sergey V. Mordanov, Elmira P. Adilgereeva, S. A. Smirnikhina, Oksana A. Ustaeva, Oleg Shukhov, Yuriy V. Shatokhin, Ekaterina Chelysheva, Alexander Lavrov, and Anna G. Turkina

Subjects
Male, 0301 basic medicine, Kinase Inhibitors, lcsh:Medicine, Biochemistry, Tyrosine-kinase inhibitor, Hematologic Cancers and Related Disorders, Fusion gene, 0302 clinical medicine, Drug Metabolism, hemic and lymphatic diseases, Medicine and Health Sciences, Copy-number variation, Enzyme Inhibitors, lcsh:Science, Glutathione Transferase, Multidisciplinary, ABL, Chromatographic Techniques, breakpoint cluster region, Myeloid leukemia, Genomics, Hematology, Middle Aged, Prognosis, Myeloid Leukemia, Glutathione, Copy Number Variation, Treatment Outcome, Oncology, Amino Acid Specific Chromatography, 030220 oncology & carcinogenesis, Female, Tyrosine kinase, Research Article, Adult, Acute Myeloid Leukemia, DNA Copy Number Variations, medicine.drug_class, Chronic Myeloid Leukemia, Tyrosine Kinase Inhibitors, Biology, Genome Complexity, Research and Analysis Methods, Young Adult, Cytogenetics, 03 medical and health sciences, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemias, Biomarkers, Tumor, Genetics, Glutathione Chromatography, medicine, Humans, Pharmacokinetics, Protein Kinase Inhibitors, Aged, Pharmacology, Myeloproliferative Disorders, Affinity Chromatography, lcsh:R, Wild type, Biology and Life Sciences, Computational Biology, Cancers and Neoplasms, 030104 developmental biology, Drug Resistance, Neoplasm, Case-Control Studies, Immunology, Enzymology, Cancer research, Cytochromes, lcsh:Q, Peptides
Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of BCR/ABL fusion gene in leukemic cells, which promotes uncontrolled cell proliferation. Up to 20% of CML patients show primary resistance or non-optimal response to tyrosine kinase inhibitor (TKI) therapy. We investigated the association between copy number variation (CNV) in glutathione S-transferases (GST) and cytochromes (CYP) and the response rate to TKI. We enrolled 47 patients with CML: 31 with an optimal response and 16 with failure at 6 months in accordance with European LeukemiaNet 2013 recommendations. CNV detection was performed using SALSA MLPA P128-C1 Cytochrome P450 probe mix. Patients with optimal response and with failure of TKI therapy showed different frequencies of wild type and mutated CYPs and GST (p

Published
2017

11. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance

Author

Sarit Assouline, Dong-Wook Kim, Vikram Mathews, Jie Jin, Zhi Xiang Shen, Edo Vellenga, H. Jean Khoury, Ricardo Pasquini, Andrey Zaritskey, Hagop M. Kantarjian, Simon Durrant, Tim H. Brümmendorf, Jorge E. Cortes, Anna G. Turkina, Francisco Cervantes, Carlo Gambacorti-Passerini, Kathleen Turnbull, Eric Leip, Tamas Masszi, Virginia Kelly, Nadine Besson, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), GAMBACORTI PASSERINI, C, Brümmendorf, T, Kim, D, Turkina, A, Masszi, T, Assouline, S, Durrant, S, Kantarjian, H, Khoury, H, Zaritskey, A, Shen, Z, Jin, J, Vellenga, E, Pasquini, R, Mathews, V, Cervantes, F, Besson, N, Turnbull, K, Leip, E, Kelly, V, and Cortes, J

Subjects
Male, DIAGNOSED CHRONIC-PHASE, NILOTINIB, DURABLE CYTOGENETIC RESPONSES, Gastroenterology, Piperazines, hemic and lymphatic diseases, Aged, 80 and over, DASATINIB, Hematology, Aniline Compounds, CHRONIC MYELOGENOUS LEUKEMIA, Myeloid leukemia, Middle Aged, Dasatinib, Treatment Outcome, Benzamides, Leukemia, Myeloid, Chronic-Phase, Imatinib Mesylate, Quinolines, Female, TRIAL, Bosutinib, Complete Hematologic Response, medicine.drug, Adult, medicine.medical_specialty, Adolescent, ABL, INHIBITION, Antineoplastic Agents, chronic myeloid leukemia CML, Disease-Free Survival, Young Adult, Internal medicine, Nitriles, medicine, Humans, Protein Kinase Inhibitors, Aged, Dose-Response Relationship, Drug, business.industry, Imatinib, Original Articles, medicine.disease, THERAPY FAILURE, Surgery, Pyrimidines, Nilotinib, Drug Resistance, Neoplasm, SKI-606, business, Chronic myelogenous leukemia, Follow-Up Studies
Abstract

Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib as second-line therapy in 288 patients with chronic phase CML resistant (n = 200) or intolerant (n = 88) to imatinib. The cumulative response rates to bosutinib were as follows: 85% achieved/maintained complete hematologic response, 59% achieved/maintained major cytogenetic response (including 48% with complete cytogenetic response), and 35% achieved major molecular response. Responses were durable, with 2-year estimates of retaining response >70%. Two-year probabilities of progression-free survival and overall survival were 81% and 91%, respectively. The most common toxicities were primarily gastrointestinal adverse events (diarrhea [84%], nausea [45%], vomiting [37%]), which were primarily mild to moderate, typically transient, and first occurred early during treatment. Thrombocytopenia was the most common grade 3/4 hematologic laboratory abnormality (24%). Outcomes were generally similar among imatinib-resistant and imatinib-intolerant patients and did not differ with age. The longer-term results of the present analysis confirm that bosutinib is an effective and tolerable second-line therapy for patients with imatinib-resistant or imatinib-intolerant chronic phase CML. http://ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00261846","term_id":"NCT00261846"}}NCT00261846. Am. J. Hematol. 89:732–742, 2014. © 2014 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.

Published
2014

12. Treatment and outcome of 2 904 CML patients from the EUTOS population based registry

Author

Gert J. Ossenkoppele, Dubravka Sertić, Perttu Koskenvesa, L.F. Casado, Doris Lindoerfer, F. Di Raimondo, Andrzej Hellmann, Andrija Bogdanovic, Verena S. Hoffmann, Irena Preloznik Zupan, Daniela Zackova, Laimonas Griskevicius, Fausto Castagnetti, Karel Indrak, Sonja Burgstaller, Martin Höglund, Michele Baccarani, Andrey Zaritskey, Ruediger Hehlmann, Joelle Guilhot, Paul Costeas, Anna G. Turkina, Sandra Lejniece, Tomasz Sacha, Richard E. Clark, Joerg Hasford, Andreas Hochhaus, Susanne Saussele, Zuzana Sninská, Gabriele Schubert-Fritschle, Hele Everaus, Gianantonio Rosti, Bengt Simonsson, Hoffmann, V.S, Baccarani, M., Hasford, J., Castagnetti, F., Di Raimondo, F., Casado, L.F., Turkina, A., Zackova, D., Ossenkoppele, G., Zaritskey, A., Höglund, M., Simonsson, B., Indrak, K., Sninska, Z., Sacha, T., Clark, R., Bogdanovic, A., Hellmann, A., Griskevicius, L., Schubert-Fritschle, G., Sertic, D., Guilhot, J., Lejniece, S., Zupan, I., Burgstaller, S., Koskenvesa, P., Everaus, H., Costeas, P., Lindoerfer, D., Rosti, G., Saussele, S., Hochhaus, A., Hehlmann, R., CCA - Cancer Treatment and quality of life, and Hematology

Subjects
Adult, Male, medicine.medical_specialty, Cancer Research, Adolescent, Population, 03 medical and health sciences, European LeukemiaNet, Young Adult, 0302 clinical medicine, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Registries, education, Survival analysis, Aged, Aged, 80 and over, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Imatinib, Hematology, Middle Aged, Survival Analysis, 3. Good health, Surgery, Dasatinib, Clinical trial, Europe, Treatment Outcome, Anesthesiology and Pain Medicine, Oncology, Nilotinib, 030220 oncology & carcinogenesis, Population Surveillance, Female, business, 030215 immunology, medicine.drug, Follow-Up Studies
Abstract

The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.

Published
2016
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13. Use of dasatinib in chronic myeloid leukemia therapy

Author

Anna G. Turkina, N. D. Choroshko, and O. Yu. Vinogradova

Subjects
Dasatinib, business.industry, medicine, Cancer research, Molecular Medicine, Myeloid leukemia, Medicine, business, medicine.drug
Published
2008

14. The EUTOS population-based registry : incidence and clinical characteristics of 2904 CML patients in 20 European Countries

Author

G. Guidi, Michele Baccarani, F. Di Raimondo, Gabriele Schubert-Fritschle, Fausto Castagnetti, J-L Steegmann, Bengt Simonsson, A. Covelli, Tomasz Sacha, Irena Preloznik Zupan, Joelle Guilhot, Andrija Bogdanovic, Verena S. Hoffmann, Karel Indrak, Sandra Lejniece, Dubravka Sertić, Ruediger Hehlmann, Sonja Burgstaller, Richard E. Clark, Noortje Thielen, Perttu Koskenvesa, Joerg Hasford, Andrey Zaritskey, Zuzana Sninská, Laimonas Griskevicius, Hele Everaus, Paul Costeas, Anna G. Turkina, Jiří Mayer, Doris Lindoerfer, Andrzej Hellmann, Hematology, CCA - Innovative therapy, Hoffmann, V.S, Baccarani, M., Hasford, J., Lindoerfer, D., Burgstaller, S., Sertic, D., Costeas, P., Mayer, J., Indrak, K., Everaus, H., Koskenvesa, P., Guilhot, J., Schubert-Fritschle, G., Castagnetti, F., Di Raimondo, F., Lejniece, S., Griskevicius, L., Thielen, N., Sacha, T., Hellmann, A., Turkina, A.G., Zaritskey, A., Bogdanovic, A., Sninska, Z., Zupan, I., Steegmann, J.-L., Simonsson, B., Clark, R.E., Covelli, A., Guidi, G., and Hehlmann, R.

Subjects
Adult, Male, Registrie, medicine.medical_specialty, Pediatrics, Cancer Research, Prognosi, Population, Alpha interferon, Follow-Up Studie, Cohort Studies, Young Adult, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Epidemiology, Medicine, Humans, Registries, Young adult, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Medicine (all), Hematology, Middle Aged, medicine.disease, Prognosis, 3. Good health, Europe, Anesthesiology and Pain Medicine, Oncology, Observational study, Female, Cohort Studie, business, Cohort study, Chronic myelogenous leukemia, Follow-Up Studies, Human
Abstract

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.

Published
2015
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15. Exome, transcriptome and miRNA analysis don’t reveal any molecular markers of TKI efficacy in primary CML patients

Author

Alexander V. Lavrov, Ekaterina Yu. Chelysheva, Elmira P. Adilgereeva, Oleg A. Shukhov, Svetlana A. Smirnikhina, Konstantin S. Kochergin-Nikitsky, Valentina D. Yakushina, Grigory A. Tsaur, Sergey V. Mordanov, Anna G. Turkina, and Sergey I. Kutsev

Subjects
Chronic myeloid leukemia, TKI efficacy, Exome, Transcriptome, miRNA analysis, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Approximately 5–20% of chronic myeloid leukemia (CML) patients demonstrate primary resistance or intolerance to imatinib. None of the existing predictive scores gives a good prognosis of TKI efficacy. Gene polymorphisms, expression and microRNAs are known to be involved in the pathogenesis of TKI resistance in CML. The aim of our study is to find new molecular markers of TKI therapy efficacy in CML patients. Methods Newly diagnosed patients with Ph+ CML in chronic phase were included in this study. Optimal and non-optimal responses to TKI were estimated according to ELN 2013 recommendation. We performed genotyping of selected polymorphisms in 62 blood samples of CML patients, expression profiling of 33 RNA samples extracted from blood and miRNA profiling of 800 miRNA in 12 blood samples of CML patients. Results The frequencies of genotypes at the studied loci did not differ between groups of patients with an optimal and non-optimal response to TKI therapy. Analysis of the expression of 34,681 genes revealed 26 differently expressed genes (p

Published
2019
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16. Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia.

Author

Alexander V Lavrov, Oksana A Ustaeva, Elmira P Adilgereeva, Svetlana A Smirnikhina, Ekaterina Y Chelysheva, Oleg A Shukhov, Yuriy V Shatokhin, Sergey V Mordanov, Anna G Turkina, and Sergey I Kutsev

Subjects
Medicine, Science
Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of BCR/ABL fusion gene in leukemic cells, which promotes uncontrolled cell proliferation. Up to 20% of CML patients show primary resistance or non-optimal response to tyrosine kinase inhibitor (TKI) therapy. We investigated the association between copy number variation (CNV) in glutathione S-transferases (GST) and cytochromes (CYP) and the response rate to TKI. We enrolled 47 patients with CML: 31 with an optimal response and 16 with failure at 6 months in accordance with European LeukemiaNet 2013 recommendations. CNV detection was performed using SALSA MLPA P128-C1 Cytochrome P450 probe mix. Patients with optimal response and with failure of TKI therapy showed different frequencies of wild type and mutated CYPs and GST (p

Published
2017
Full Text
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