CML: definition. CML epidemiology. CML diagnosis. CML: peripheralbloodsmear. Cytogenetic abnormality of CML
|
|
- Mildred Hudson
- 5 years ago
- Views:
Transcription
1 MolecularDiagnostic.be Third Scientific Meeting Molecular Diagnostics.be t(9;22) CML: definition Management of CML patients treated with TKI: the place of molecular monitoring Antwerp, December 13 th 11 C. Graux CHU Mont-Godinne CML epidemiology CML diagnosis CML accounts for 14% of all leukemias The incidence is 1.6 per 1. /year +/- new cases/ year in Belgium 1 CML = 2 AML = 3 MM = 12 NHL = 37 CLL Increases with age(median 67 y) Male predominance: 1.4/1 The only known risk factor is ionizing radiations (high doses) Exposure to atomic bomb in Nagasaki and Hiroshima induced CML Symptoms - Fatigue, anorexia, weight loss Clinical examination - Splenomegaly Biology - Hyperleucocytosis - Circulating bone marrow myeloid precursors (left shift) - Increased basophilia -Thrombocytosis Cytogenetics: t(9;22) = Philadelphia (Ph) chromosome Molecular biology: BCR-ABL1 CML: peripheralbloodsmear Cytogenetic abnormality of CML Normal Chronic phase of CML x Y Ph chromosome 1
2 Ph chromosome and BCR-ABL1 gene BCR-ABL1: types of transcripts 9 9 q+ Chromosome 22 Chromosome 9 1a BCR ABL1 m-bcr 55 kd 1b 22 Ph(or 22q-) P21 BCR-ABL1 M-bcr 2,9 kb a2 a3 P19 BCR-ABL1 ABL1 BCR BCR-ABL1 Chimeric protein with tyrosine kinase activity Exons Introns CML Breakpoints ALL Breakpoint µ-bcr t(9;22) translocation BCR-ABL1 gene structure Multiplex-PCR for BCR-ABL1 transcripts Constitutively activated tyrosine kinase BCR BCR-ABL1 Bcr-Abl1 signal transduction pathways Clinical evolution : CML phases BCR-ABL1 JAK/STATs DNA repair GRB2 CRKL CBL(p1 CBL ) Actin Adhesion Chronic phase Accelerated phase Advanced phases Blastic crisis RAS Paxillin Adhesion PI3 kinase AKT Variable Median time 6 9 months Median survival 3 6 months RAF-MEK-MAPK cascade MYC BCL-2 Regulates cell cycle progression and differentiation Inhibition of apoptosis Adapted from Pasternak G et al. J Cancer Res ClinOncol. 1998;124:
3 What are the therapeutic goals in CML? Criteria for response to R/ Disappearance of the symptoms Modify the natural evolution of the disease blastic phase Cure Hematologic response Complete -Plateletcount < 45 x 1 9 /L -WBC count < 1 x 1 9 /L -Differential: no immature granulocyte -Basophils< 5% -Non palpable spleen Cytogenetic response Complete(CCgR) = No Ph+ metaphases Partial(PCgR) = 1-35% Ph+ metaphases Minor= 36-65% Ph+ metaphases Minimal= 66-95% Ph+ metaphases None = > 95% Ph+ metaphases Molecular response Allogeneic SCT Interferon α National Marrow Donor Program (NMDP) overview slide presentation. Available at Accessed 17 June 2. P =.1 Survival by disease stage, June 1, based on transplants 1987 Feb 1. Proportion surviving P <.1 Major cytogenetic response Minor or no response The only known cure but is associated with high morbidity and mortality rates in CML Months after treatment with IFN-α Guilhot F et al. N Engl J Med. 1997;337: Oral cytotoxic agents Chemotherapy BCR-ABL1: the ideal target for molecular therapy Hydroxyurea Busulfan Hematological responses in up to 9% of patients Major cytogenetic responses are rare (1% 5%) 1-4 Palliative care: no effect on disease progression Present in the majority of patients with CML (95%) The cause of the disease Necessary for the initiation of the disease (primary event) ABL1 is non essential for normal cellular functions - Abl1 neg mice are viable targets BCR-ABL1 1. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. N Engl J Med. 1994;33: Hehlmann R et al. Blood. 1994;84: Allan NC et al. Lancet. 1995;345: Ohnishi K et al. Blood. 1995;86:
4 Mechanism of action of IRIS Study versus IFN-α + Ara-C 116 patients enrolled from June to January 1 S R IF: Loss of MCyR or CHR Increasing WBC count Intolerance of treatment Failure to achieve MCyR Cross-over S = screening R = randomisation IFN-a+ Ara-C Progression Death Accelerated phase or blast crisis Loss of MCR or CHR Increasing WBC count Goldman JM, Melo JV. N Engl J Med. 344 : Complete hematological responses Major cytogenetic responses % Responding 1 94% % IFN-α + Ara-C Months Since Randomisation % Responding % 3 % 1 IFN-α + Ara-C Months Since Randomisation Superiority of to IFN-α+ Ara-C 1 8 IRIS Study : Summary of the 12-Month Data IFN- α+ Ara-C Is CCyR the best surrogate endpoint? ,7 1,5,7 CHR MCyR PD to AP/BC Intolerance CHR = complete haematological response; MCR = major cytogenetic response; PD = progressive disease; AP = accelerated phase; BC = blast crisis. Baccarani, M. et al. Blood 6;18:
5 Progression to AP/BP Towards cure under TKI? IRIS study Is MMR the best surrogate endpoint? No proven effect on survival Variability of the assay Data on benefit of MMR based on good responders But MMR = very low progression rate Loss of MMR signals relapse/progression Early MMR predicts complete molecular response cure? MMR underscores the basic oncology principle that less disease is better Less is probably more Molecular monitoring: difficulties RQ-PCR is technically challenging Issues concerning comparability of results between centres International standardisation of molecularmonitoring for CML to enable testing laboratories to accurately mesure key therapeutic molecular milestones in CML (MMR and CMR) International scale for BCR-ABL1 International scalefor BCR-ABL1 Historically (IRIS trial; ), the mean BCR-ABL1 levels of 3 CML patients was defined as 1% in each of the three participating laboratories using BCR as a control The value corresponding to MMR in each laboratory has been defined as,1% (reduction of 3 log from IRIS baseline) International Scale (IS) fixed to these key points The absolute and not the relative amount is important MMR is defined as,1% IS = - 3 log reduction of BCR-ABL1 from IRIS standardised baseline, NOT 3 log reduction from individual pretreatment levels 5
6 Second generation TKI Nilotinibvs. in CML-CP (ENESTnd Trial) Nilotinib vs. in CML-CP (ENESTnd Trial, NEJM 1, Lancet, 11) More frequent and faster MMR Decreased progression to accelerated or blastic phase More frequent CMR room for cure? Dasatinib vs. in CML-CP (NEJM 1) More CCyR More frequent and faster MMR Effect on long term outcome? BCR-ABL1 kinase domain mutants BCR-ABL1 kinase domain mutants Are associated with various degrees of TKI insensitivity Select resistant clones = most important mechanism of resistance Can precede or accompany progression to advanced-phase disease KD mutations above a certain level should be identified as early as possible to reconsider the therapeutic strategy 9 KD mutations known to date Martinelli. The Hematology Journal, 5 Activity of Nilotinib on -Resistant BCR-ABL1 Mutants Spectrum of Kinase Inhibition for and Novel Compounds 3 IC5 (nm) on proliferation Gleevec AMN17 maternal + IL3 bcr-abl wt M237I M244V L248V G25A G25E G25V Q252H Y253H E255D E255K E255V E255R E275K E276G E281K K285N E292K F311V T315I F317C F317L F317V D325N S348L M351T E355A E355G F359C F359V A38S L387F M388L F468S 72-hour proliferation assay with BCR-ABL expressing Ba/F3 cells (ATPLite; Perkin Elmer). Trough levels at a dose of 4 mg twice daily (BID) (1.7 µm) exceed the IC 5 determined in vitro for 32/33 BCR-ABL mutants (exception T315I) Weisberg et al. Br J Cancer. 6;94:1765. Melo J, Hematology 9 6
7 Management of CML Recommendations from the European LeukemiaNet Conclusion Time Optimal response Suboptimal response Failure Warnings Diagnosis N/A N/A N/A High risk CCA/Ph+ 3 months CHR, atleast Minor CgR No CgR LessthanCHR N/A The next step is - to better define CMR (EUTOS project) 6 months Atleast PCgR LessthanPCgR No CgR N/A 12 months CCgR PCgR LessthanPCgR LessthanMMR 18 months MMR LessthanMMR LessthanCCgR N/A Anytime (during treatment) Stable or improving MMR Lossof MMR Mutations (IM-sensit) Lossof CHR, lossof CCgR, mutations (IM-insensit) CCA/Ph+ Increasein transcript levels CCA/Ph- - to identify patients cohorts not relapsing after TKI withdrawal New recommendations 1 are marked in red. 7
A 34-year old women came because of abdominal discomfort. Vital sign was stable. Spleen tip was palpable.
1 Case 1 A 34-year old women came because of abdominal discomfort. Vital sign was stable. Spleen tip was palpable. CBC and bone marrow aspiration and biopsy were done. Chromosome study showed she had t(9;22)
More informationThe BCR-ABL1 fusion. Epidemiology. At the center of advances in hematology and molecular medicine
At the center of advances in hematology and molecular medicine Philadelphia chromosome-positive chronic myeloid leukemia Robert E. Richard MD PhD rrichard@uw.edu robert.richard@va.gov Philadelphia chromosome
More informationForm 2012 R3.0: Chronic Myelogenous Leukemia (CML) Pre-Infusion Data
Form 2012 R3.0: Chronic Myelogeus Leukemia (CML) Pre-Infusion Data Key Fields Sequence Number: Date Received: - - CIBMTR Center Number: CIBMTR Research ID: Event date: - - HCT type: (check all that apply)
More informationELN Recommendations on treatment choice and response. Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy
ELN Recommendations on treatment choice and response Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy ELN 2013 Response to Front-line Treatment Baseline 3 months 6 months OPTIMAL
More informationNew drugs and trials. Andreas Hochhaus
New drugs and trials. Andreas Hochhaus Hadera I Oct 2018 Introduction ABL001 is a potent, specific inhibitor of BCR-ABL1 with a distinct allosteric mechanism of action BCR-ABL1 Protein Binds a distinct
More informationHistory of CML Treatment
History of CML Treatment Eduardo Olavarria No conflict of interest Lisbon, 20th March 2018 #EBMT18 www.ebmt.or What is CML? The mystery of chronic myeloid leukaemia Chronic myeloid leukaemia Often diagnosed
More informationCML and Future Perspective. Hani Al-Hashmi, MD
CML and Future Perspective Hani Al-Hashmi, MD Objectives Learning from CML history Outcome of interest to clinician Patient and community interest!! Learning from CML history Survival Probability (All
More informationSESSION III: Chronic myeloid leukemia PONATINIB. Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy
SESSION III: Chronic myeloid leukemia PONATINIB Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy Ponatinib A Pan-BCR-ABL Inhibitor Rationally designed inhibitor of BCR- ABL
More informationWhat is the optimal management strategy for younger CP-CML patients with matched, related donors who fail to achieve CCyR
What is the optimal management strategy for younger CP-CML patients with matched, related donors who fail to achieve CCyR after 18 months of imatinib? Second generation TKIs as a bridge to allogeneic SCT
More informationWhen to change therapy? Andreas Hochhaus Universitätsklinikum Jena, Germany
When to change therapy? Andreas Hochhaus Universitätsklinikum Jena, Germany Chromosome 22 Chromosome 9 e1 1b m-bcr M-bcr e1 e2 b1 b5 5 3 BCR ABL 5 3 1a a2 a3 μ -bcr e19 a11 e1a2 b2a2 b3a2 e19a2 p190 bcr-abl
More informationChronic Myeloid Leukaemia
Chronic Myeloid Leukaemia Molecular Response: What is really important? Jeff Szer The Royal Melbourne Hospital PROBABILITY, % PROBABILITY OF SURVIVAL AFTER MYELOABLATIVE TRANSPLANTS FOR CML IN CHRONIC
More informationWhat Can We Expect from Imatinib? CML Case Presentation. Presenter Disclosure Information. CML Case Presentation (cont)? Session 2: 8:15 AM - 9:00 AM
Welcome to Master Class for Oncologists Session 2: 8:15 AM - 9: AM Miami, FL December 18, 29 Chronic Myelocytic Leukemia: Imatinib and Beyond Speaker: Daniel J. DeAngelo, MD, PhD Dana-Farber Cancer Institute
More informationVenice Meeting Highlights: Key lessons. Conclusions Michele Baccarani Rüdiger Hehlmann
Venice Meeting Highlights: Key lessons Conclusions Michele Baccarani Rüdiger Hehlmann CML therapy in the imatinib era CML prognosis has improved dramatically Cellular and molecular biology studies help
More informationRole of Second Generation Tyrosine Kinase Inhibitors in Newly Diagnosed CML. GIUSEPPE SAGLIO, MD University of Torino, Italy
Role of Second Generation Tyrosine Kinase Inhibitors in Newly Diagnosed CML GIUSEPPE SAGLIO, MD University of Torino, Italy Outcome in 282 Patients Treated with Imatinib First Line in Hammersmith Hospital
More informationChronic Myeloid Leukemia A Disease of Young at Heart but Not of Body
Chronic Myeloid Leukemia A Disease of Young at Heart but Not of Body Jeffrey H Lipton, PhD MD FRCPC Staff Physician, Princess Margaret Cancer Centre Professor of Medicine University of Toronto POGO November,
More informationEUROPEAN LEUKEMIANET RECOMMENDATIONS FOR CHRONIC MYELOID LEUKEMIA
EUROPEAN LEUKEMIANET RECOMMENDATIONS FOR CHRONIC MYELOID LEUKEMIA SAN DIEGO, 11 DECEMBER 2011 AMSTERDAM, 14 JUNE 2012 BALTIMORE, 20 SEPTEMBER 2012 ATLANTA, 6 DECEMBER 2012 ELN, CML Panel Jane Apperley
More informationHOW I TREAT CML. 4. KONGRES HEMATOLOGOV IN TRANSFUZIOLOGOV SLOVENIJE Z MEDNARODNO UDELEŽBO Terme Olimia, Podčetrtek,
HOW I TREAT CML 4. KONGRES HEMATOLOGOV IN TRANSFUZIOLOGOV SLOVENIJE Z MEDNARODNO UDELEŽBO Terme Olimia, Podčetrtek, 12. - 14. april, 2012 Gianantonio Rosti Dpt of Hematology and Oncological Sciences S.
More informationCurrent Monitoring for CML: Goals and. Jorge Cortes, MD Chief, CML & AML Section Department of Leukemia MD Anderson Cancer Center
Current Monitoring for CML: Goals and Principles Jorge Cortes, MD Chief, CML & AML Section Department of Leukemia MD Anderson Cancer Center Survival in Early Chronic Phase CML MDACC 2009 The Philadelphia
More information2nd generation TKIs to first line therapy
New Horizons 2011 Newly diagnosed CML moving 2nd generation TKIs to first line therapy Gianantonio Rosti Dept. Of Hematology and Oncology St. Orsola-Malpighi University Hospital Bologna (Italy) GIMEMA
More information10 YEARS EXPERIENCE OF TYROSINE KINASE INHIBITOR THERAPY FOR CML IN OXFORD
10 YEARS EXPERIENCE OF TYROSINE KINASE INHIBITOR THERAPY FOR CML IN OXFORD Dalia Khan 1, Noemi Roy 1, Vasha Bari 1, Grant Vallance 1, Helene Dreau 1, Timothy Littlewood 1, Andrew Peniket 1, Paresh Vyas
More informationCML CML CML. tyrosine kinase inhibitor CML. 22 t(9;22)(q34;q11) chronic myeloid leukemia CML ABL. BCR-ABL c- imatinib mesylate CML CML BCR-ABL
1 Key Wordschronic myeloid leukemiaimatinib mesylate tyrosine kinase inhibitor chronic myeloid leukemia CML imatinib mesylate CML CML CML CML Ph 10 1 30 50 3 5 CML α IFNα Ph Ph cytogenetic response CRmajor
More informationGuidelines and real World: Management of CML in chronic and advanced phases. Carolina Pavlovsky. FUNDALEU May 2017 Frankfurt
Guidelines and real World: Management of CML in chronic and advanced phases Carolina Pavlovsky. FUNDALEU 26-28 May 217 Frankfurt Some Issues in CML 217 First Line treatment: Imatinib vs 2nd generation
More informationscreening procedures Disease resistant to full-dose imatinib ( 600 mg/day) or intolerant to any dose of imatinib
Table S1. Study inclusion and exclusion criteria Inclusion criteria Aged 18 years Signed and dated informed consent form prior to protocol-specific screening procedures Cytogenetic- or PCR-based diagnosis
More informationIRIS 8-Year Update. Management of TKI Resistance Will KD mutations matter? Sustained CCyR on study. 37% Unacceptable Outcome 17% 53% 15%
Management of TKI Resistance Will KD mutations matter? IRIS 8-Year Update 17% 53% 5% 15% 37% Unacceptable Outcome No CCyR Lost CCyR CCyR Other 3% 7% Safety Lost-regained CCyR Sustained CCyR on study Deininger
More informationHow I treat high risck CML
Torino, September 14, 2018 How I treat high risck CML Patrizia Pregno Hematology Dept. Citta della Salute e della Scienza Torino Disclosures Advisory Board: Novartis, Pfizer, Incyte Speaker Honoraria:
More informationNEW DRUGS IN HEMATOLOGY
NEW DRUGS IN HEMATOLOGY BOLOGNA, 15-17 April 2013 TYROSINE KINASE INHIBITORS IN CHRONIC MYELOID LEUKEMIA MICHELE BACCARANI michele.baccarani@unibo.it Historic Development of CML Therapy Palliative Therapy
More informationC Longer follow up on IRIS data
hronic Myeloid Leukemia Drs. Rena Buckstein, Mervat Mahrous & Eugenia Piliotis with input from Dr. J. Lipton (PMH) Updated August 2008* Updates: C Longer follow up on IRIS data Guidelines for monitoring
More informationStarting & stopping therapy in Chronic Myeloid Leukemia: What more is needed? Richard A. Larson, MD University of Chicago March 2019
Starting & stopping therapy in Chronic Myeloid Leukemia: What more is needed? Richard A. Larson, MD University of Chicago March 2019 Disclosures Richard A. Larson, MD Research funding to the University
More informationIS MUTATION ANALYSIS OF BCR-ABL OF ANY VALUE IN CLINICAL MANAGEMENT OF CML PATIENTS? David Marin, Imperial College London
IS MUTATION ANALYSIS OF BCR-ABL OF ANY VALUE IN CLINICAL MANAGEMENT OF CML PATIENTS? David Marin, Imperial College London Tell me generals, are we politicians necessary? I have to admit defeat before starting
More informationManagement of CML in blast crisis. Lymphoma Tumor Board November 27, 2015
Management of CML in blast crisis Lymphoma Tumor Board November 27, 2015 Chronic Phase CML - 2. Peter Maslak, ASH Image Bank 2011; 2011-2455 Copyright 2011 American Society of Hematology. Copyright restrictions
More informationFuture of CML: ABL001 and other treatments in the pipeline. Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy
Future of CML: ABL001 and other treatments in the pipeline. Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy Primitive sleeping BCR-ABL-positive leukemic stem cells are less
More informationCML Clinical Case Scenario
CML Clinical Case Scenario Neil Shah, MD, PhD Edward S. Ageno Distinguished Professor in Hematology/Oncology Leader, Hematopoietic Malignancies Program Helen Diller Family Comprehensive Cancer Center at
More informationCML David L Porter, MD University of Pennsylvania Medical Center Abramson Cancer Center CML Current treatment options for CML
1 CML 2012 LLS Jan 26, 2012 David L Porter, MD University of Pennsylvania Medical Center Abramson Cancer Center CML 2012 Current treatment options for CML patients Emerging therapies for CML treatment
More informationMRD in CML (BCR-ABL1)
MRD in CML (BCR-ABL1) Moleculaire Biologie en Cytometrie cursus Barbara Denys LAbo Hematologie UZ Gent 6 mei 2011 2008 Universitair Ziekenhuis Gent 1 Myeloproliferative Neoplasms o WHO classification 2008:
More informationMolecular Detection of BCR/ABL1 for the Diagnosis and Monitoring of CML
Molecular Detection of BCR/ABL1 for the Diagnosis and Monitoring of CML Imran Mirza, MD, MS, FRCPC Pathology & Laboratory Medicine Institute Sheikh Khalifa Medical City, Abu Dhabi, UAE. imirza@skmc.ae
More informationOutlook CML 2016: What is being done on the way to cure
New Horizons 2011 Outlook CML 2016: What is being done on the way to cure Gianantonio Rosti Dept. Of Hematology and Oncology St. Orsola-Malpighi University Hospital Bologna (Italy) GIMEMA CML Working Party
More informationNew drugs in first-line therapy
New drugs in first-line therapy Gianantonio Rosti Dept of Hematology and Oncology Seràgnoli, Bologna University (Italy) GIMEMA (Gruppo Italiano Malattie Ematologiche dell Adulto) CML WORKING PARTY IRIS
More informationEVI-1 oncogene expression predicts survival in chronic phase CML patients resistant to imatinib
EVI-1 oncogene expression predicts survival in chronic phase CML patients resistant to imatinib Mustafa Daghistani Department of Haematology, Imperial College London at Hammersmith Hospital, Du Cane Road,
More informationWhat is New in CML in Hagop Kantarjian, M.D. February 2011
What is New in CML in 2011 Hagop Kantarjian, M.D. February 2011 1 CML. Historical vs. Modern Perspective Parameter Historical Modern Course Fatal Indolent Prognosis Poor Excellent 10-yr survival 10% 84-90%
More informationThe concept of TFR (Treatment Free Remission) in CML
The concept of TFR (Treatment Free Remission) in CML Giuseppe Saglio University of Turin, Italy What can we expect today on long-term therapy with TKIs in CML? German CML study IV Relative and overall
More informationAGGIORNAMENTI IN EMATOLOGIA Faenza, 7 Giugno 2018 LMC: ALGORITMI TERAPEUTICI ATTUALI E IL PROBLEMA DELLA RESISTENZA.
AGGIORNAMENTI IN EMATOLOGIA Faenza, 7 Giugno 2018 LMC: ALGORITMI TERAPEUTICI ATTUALI E IL PROBLEMA DELLA RESISTENZA Michele.Baccarani@unibo.it EUROPEAN LEUKEMIANET 2013 (Blood 2013;122:885 892). RESPONSE
More informationCML TREATMENT GUIDELINES
CML TREATMENT GUIDELINES INITIAL INVESTIGATION Propose enrolment in the CML Registry of the CML-MPN Quebec Research Group. Medical history : Question for cardio-respiratory disorders, diabetes, pancreatitis,
More informationMolecular monitoring of CML patients
EHA, Education Session, CML Stockholm, 14 June 2013 Molecular monitoring of CML patients Martin C. Müller Medical Faculty Mannheim Ruprecht-Karls-University Heidelberg Mannheim, Germany Disclosures Research
More informationShould nilotinib replace imatinib as first line treatment of chronic myeloid leukemia in chronic phase (CML-CP)?
Should nilotinib replace imatinib as first line treatment of chronic myeloid leukemia in chronic phase (CML-CP)? http://test.metromomsblog.org/wp-content/uploads/2010/02/tortoise-and-the-hare.jpg D. Van
More informationMyeloproliferative Disorders - D Savage - 9 Jan 2002
Disease Usual phenotype acute leukemia precursor chronic leukemia low grade lymphoma myeloma differentiated Total WBC > 60 leukemoid reaction acute leukemia Blast Pro Myel Meta Band Seg Lymph 0 0 0 2
More informationStopping TKI s in CML- Are we There Yet? Joseph O. Moore, MD Duke Cancer Institute
Stopping TKI s in CML- Are we There Yet? Joseph O. Moore, MD Duke Cancer Institute Natural History of CML Accumulation of immature myeloid cells New cytogenetic changes Chronic Phase Accelerated Phase
More informationJuan Luis Steegmann Hospital de la Princesa. Madrid. JL Steegmann
Juan Luis Steegmann Hospital de la Princesa. Madrid. Juan Luis Steegmann Hospital de la Princesa. Madrid No rush,at least in Chronic Phase Blast Phase*: SCT asap, after restablishing CP with TKI Accelerated
More informationContemporary and Future Approaches in CML. Emory Meeting; Sea Island August 2014 Hagop Kantarjian, M.D.
Contemporary and Future Approaches in CML Emory Meeting; Sea Island August 2014 Hagop Kantarjian, M.D. 1 CML. Historical vs. Modern Perspective Parameter Historical Modern Course Fatal Indolent Prognosis
More informationCML: Yesterday, Today and Tomorrow. Jorge Cortes, MD Chief CML Section Department of Leukemia The University of Texas, M.D. Anderson Cancer Center
CML: Yesterday, Today and Tomorrow Jorge Cortes, MD Chief CML Section Department of Leukemia The University of Texas, M.D. Anderson Cancer Center Five Years of Signal Transduction Inhibition The Beginning
More informationCML Update 2016 Arthur 2016
CML Update 2016 Chronic Myeloid Leukemia Splenomegaly CML (3 phase disease) Increased white cells Malignant proliferation of myeloid white cells Initially mature cells a) chronic phase of disease Evolution
More informationCML: Living with a Chronic Disease
CML: Living with a Chronic Disease Jorge Cortes, MD Chief, CML and AML Sections Department of Leukemia M. D. Anderson Cancer Center Houston, Texas Survival in Early Chronic Phase CML TKI Interferon Chemotherapy
More informationChronic myeloid leukemia (CML) Warunsuda Sripakdee, BCOP,BCP Prince of Songkla University
Chronic myeloid leukemia (CML) 1 Warunsuda Sripakdee, BCOP,BCP Prince of Songkla University Hematologic malignancies CML ALL AML 2 CML CD34+ results from an acquired mutation that affects hematopoietic
More informationBlast Phase Chronic Myelogenous Leukemia
Blast Phase Chronic Myelogenous Leukemia Benjamin Powers, MD; and Suman Kambhampati, MD The dramatic improvement in survival with tyrosine kinase inhibitors has not been demonstrated in the advanced blast
More informationLa terapia della LMC: è possibile guarire senza trapianto? Fabrizio Pane
La terapia della LMC: è possibile guarire senza trapianto? Fabrizio Pane What could be the concept of Cure in CML? Sustained DMR with or without TKI therapy And 100% CML-related survival And QoL comparable
More informationState of the Art Therapy and Monitoring of CML Hagop Kantarjian, M.D. Grand Rounds Hackensack, New Jersey. September 22, 2010
State of the Art Therapy and Monitoring of CML - 2010 Hagop Kantarjian, M.D. Grand Rounds Hackensack, ew Jersey September 22, 2010 1 CML. Historical vs. Modern Perspective Parameter Historical Modern Course
More information2 nd Generation TKI Frontline Therapy in CML
2 nd Generation TKI Frontline Therapy in CML Elias Jabbour, M.D. April 212 New York Frontline Therapy of CML in 212 - imatinib 4 mg daily - nilotinib 3 mg BID - dasatinib 1 mg daily Second / third line
More information1794 Updating Long-Term Outcome of Intermittent Imatinib. (INTERIM) Treatment in Elderly Patients with Ph+-CML
738 What Is the Most Cost-Effective Strategy for Treating Newly Diagnosed Chronic Phase Chronic Myeloid Leukaemia (CML) after Imatinib Loses Patent Exclusivity? https://ash.confex.com/ash/2014/webprogram/paper71699.html
More informationCIBMTR Center Number: CIBMTR Recipient ID: Today s Date: Date of HSCT for which this form is being completed:
Chronic Myelogenous Leukemia (CML) Post-HSCT Data Sequence Number: Date Received: Registry Use Only Today s Date: Date of HSCT for which this form is being completed: HSCT type: autologous allogeneic,
More informationMP BCR-ABL1 Testing in Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia
Medical Policy BCBSA Ref. Policy: 2.04.85 Last Review: 10/18/2018 Effective Date: 10/18/2018 Section: Medicine Related Policies 8.01.30 Hematopoietic Cell Transplantation for Chronic Myelogenous Leukemia
More informationThe biology of chronic myeloid leukaemia
The biology of chronic myeloid leukaemia Graduate Program Course: Biology of cancer April 2007 Myeloproliferative disorders Clonal disorders of haemopoiesis that arise in a haemopoietic stem cell or early
More informationWelcome and Introductions
Living with Chronic Myeloid Leukemia Welcome and Introductions Living with Chronic Myeloid Leukemia Living with Chronic Myeloid Leukemia (CML) Neil P. Shah, MD, PhD Edward S. Ageno Distinguished Professor
More informationIn this issue of the journal two articles deal with different
EDITORIALS & PERSPECTIVES Monitoring treatment of chronic myeloid leukemia Michele Baccarani, 1 Fabrizio Pane, 2 and Giuseppe Saglio 3 1 Department of Hematology-Oncology "L. and A. Seràgnoli" University
More informationAllogeneic SCT for. 1st TKI. Vienna Austria. Dr. Eduardo Olavarría Complejo Hospitalario de Navarra
The International Congress on Controversies in Stem Cell Transplantation and Cellular Therapies (COSTEM) Berlin, Germany September 8-11, 2011 Vienna Austria Allogeneic SCT for CML Allogeneic after failure
More informationNEW DRUGS IN HEMATOLOGY Bologna, 9-11 May 2016 CHRONIC MYELOID LEUKEMIA STATUS OF THE ART OF TREATMENT.
NEW DRUGS IN HEMATOLOGY Bologna, 9-11 May 2016 CHRONIC MYELOID LEUKEMIA STATUS OF THE ART OF TREATMENT Michele.baccarani@unibo.it Michele BACCARANI, MD Professor of Hematology at the Universities of Trieste,
More informationKwan, TK; Ma, ESK; Chan, YY; Wan, TSK; Liu, HSY; Sim, JPY; Yeung, YM; Lie, AKW; Yip, SF
Title Author(s) BCR-ABL mutational studies for predicting the response of patients with chronic myeloid leukaemia to second-generation tyrosine kinase inhibitors after imatinib fail Kwan, TK; Ma, ESK;
More informationpan-canadian Oncology Drug Review Final Clinical Guidance Report Ponatinib (Iclusig) for Chronic Myeloid Leukemia / Acute Lymphoblastic Leukemia
pan-canadian Oncology Drug Review Final Clinical Guidance Report Ponatinib (Iclusig) for Chronic Myeloid Leukemia / Acute Lymphoblastic Leukemia October 1, 2015 DISCLAIMER Not a Substitute for Professional
More informationThe speaker has no financial relationships with a commercial interest to disclose and no conflicts of interest to resolve.
Hana Safah MD Professor of Medicine Tulane University School of Medicine Director of the SCT program, Tulane Medical Center The speaker has no financial relationships with a commercial interest to disclose
More informationMolecular pathogenesis of CML: Recent insights
Napoli 24 gennaio 2012 Molecular pathogenesis of CML: Recent insights Giuseppe Saglio University of Turin CML Biology CML Clinical practice MILESTONES IN MOLECULAR BIOLOGY OF CML 1960 - Nowell P.C. & Hungerford
More informationPost ASH Actualités LMC
Post ASH 2014 - Actualités LMC Actualités de première ligne LMC PC ENESTnd (6 ans) Dasision (5 ans) EPIC Spirit France (5 ans) Spirit 2 UK (5 ans) ENESTnd: Mise à jour à 6 ans Design = 846 ults with wly
More informationChronic myeloid leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
clinical practice guidelines Annals of Oncology 23 (Supplement 7): vii72 vii77, 2012 doi:10.1093/annonc/mds228 Chronic myeloid leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
More informationTaiwan Guidelines for the Management of Chronic Myeloid Leukemia
Taiwan Guidelines for the Management of Chronic Myeloid Leukemia Taiwan CML Study Group Coordinator: Lee-Yung Shih 2013/11/30 1 Contents Initial work-up at diagnosis and define baseline prognostic factors
More informationHSCT for Myeloproliferative Disorders. Jane Apperley
HSCT for Myeloproliferative Disorders Jane Apperley Myeloproliferative disorders CML Polycythemia vera Essential thrombocythemia Primary myelofibrosis bcr-abl + bcr-abl - JAK2 (valine to phenylalanin an
More informationGreater Manchester and Cheshire Cancer Network Chronic Myeloid Leukaemia v3 2012
Greater Manchester and Cheshire Cancer Network Chronic Myeloid Leukaemia v3 2012 Dr Simon Watt Dr Shiva Natarajan 1.0 Introduction The landscape in chronic myeloid leukaemia (CML) has changed dramatically
More informationAccepted Manuscript. Improving Outcomes in Chronic Myeloid Leukemia Over Time in the Era of Tyrosine Kinase Inhibitors. Pradnya Chopade, Luke P.
Accepted Manuscript Improving Outcomes in Chronic Myeloid Leukemia Over Time in the Era of Tyrosine Kinase Inhibitors Pradnya Chopade, Luke P. Akard PII: S2152-2650(18)30343-4 DOI: 10.1016/j.clml.2018.06.029
More informationState of the Art Therapy and Monitoring of CML Hagop Kantarjian, M.D. Grand Rounds UT Southwestern. October 28, 2010
State of the Art Therapy and Monitoring of CML - 2010 Hagop Kantarjian, M.D. Grand Rounds UT Southwestern October 28, 2010 1 CML. Historical vs. Modern Perspective Parameter Historical Modern Course Fatal
More informationRESEARCH ARTICLE. Introduction. Methods Wiley Periodicals, Inc.
BCR/ABL level at 6 months identifies good risk CML subgroup after failing early molecular response at 3 months following imatinib therapy for CML in chronic phase AJH Dennis (Dong Hwan) Kim, 1 * Nada Hamad,
More informationContemporary and Future Approaches in Management of CML. Disclosures
Winship Cancer Institute of Emory University Contemporary and Future Approaches in Management of CML Hagop Kantarjian, MD Chairman and Professor, Department of Leukemia University of Texas M. D. Anderson
More informationChronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring
Received: 13 December 2017 Accepted: 17 December 2017 DOI: 10.1002/ajh.25011 ANNUAL CLINICAL UPDATES IN HEMATOLOGICAL MALIGNANCIES Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring
More informationIntroduction to Cancer
Introduction to Cancer Clonal Evolution Theory of Tumor Development,2,2,,2,2,,2, Numbers represent sequential mutations to cellular genes Oncogenes and Tumor Suppresser Genes On Oncogenes Tumor Suppresser
More informationStopping Treatment in CML and dose reduction in clinical practice: Can we do it safely? YES WE CAN!
Stopping Treatment in CML and dose reduction in clinical practice: Can we do it safely? YES WE CAN! Dragana Milojković The Hammersmith Hospital, London, UK Leukemic burden Current Aim of TKI therapy Molecular
More informationTyrosine kinase inhibitors (TKIs) act by preventing disease
SUBJECT REVIEW Emergence of BCR-ABL Kinase Domain Associated with Newly Diagnosed Chronic Myeloid Leukemia: A Meta-Analysis of Clinical Trials of Tyrosine Kinase Inhibitors Iulia D. Ursan, PharmD; Ruixuan
More informationSede Amministrativa: Università degli Studi di Padova
Sede Amministrativa: Università degli Studi di Padova Dipartimento di Scienze del Farmaco CORSO DI DOTTORATO DI RICERCA IN SCIENZE FARMACOLOGICHE CURRICOLO: FARMACOLOGIA, TOSSICOLOGIA E TERAPIA XXX CICLO
More informationDiagnosis and Management of Chronic Myeloid Leukaemia
Diagnosis and Management of Chronic Myeloid Leukaemia Dr Simon Watt Dr Katherine O Neill Dr Fiona Dignan Written July 2017 Prof Tim Somervaille Review July 2019 1 Table of Contents 1.0 Introduction 3 2.0
More informationBMS Satellite Symposium
ICKSH 2018 BMS Satellite Symposium Emerging Trends in CML Management CHAIRMAN The Head of Catholic Hematology Hospital The Director of the Catholic Leukemia Research Institute at the Catholic University
More informationChronic Myeloid Leukemia: What more is needed? Richard A. Larson, MD University of Chicago March 2018
Chronic Myeloid Leukemia: What more is needed? Richard A. Larson, MD University of Chicago March 2018 Disclosures Richard A. Larson, MD Research funding to the University of Chicago: Astellas Celgene Daiichi
More informationExecutive summary Overview
Executive summary Overview In this appraisal, we have demonstrated that dasatinib is clinically more effective, as well as more cost effective, than imatinib, the current standard of care. In the pivotal
More informationMyeloproliferative Neoplasms
Myeloproliferative Neoplasms Judit Demeter CML chronic myeloid leukemia Semmelweis University, I st Department of Internal Medicine PV polycythaemia vera ET essential thrombocythaemia MF myelofibrosis
More informationImatinib dose intensification, combination therapies. Andreas Hochhaus Universitätsklinikum Jena, Germany
Imatinib dose intensification, combination therapies Andreas Hochhaus Universitätsklinikum Jena, Germany Apperley JF. Lancet Oncol. 2007 High OCT-1 activity is associated with faster MMR in imatinib treated
More informationChronic Myeloid Leukaemia Guidelines
Chronic Myeloid Leukaemia Guidelines Approved by Pathway Board for Haematological Malignancies Coordinating author: Heather Oakervee, Bart s Health NHST Date of issue: 12.03.2015 Version number:v1.0 These
More informationCML Treatment Failure: More Threatening Than It Appears. Mutation Testing
CML Treatment Failure: More Threatening Than It Appears Mutation Testing Content Mutations and treatment failure Single mutations Compound mutations Mutation testing Guideline recommendations Summary 2
More informationDAVID S. SNYDER, M.D.
CML UPDATE 2019 DAVID S. SNYDER, M.D. MARCH 21,2019 Click to edit Master Presentation Date Disclosures I do not have anything to disclose 2001 2016 Loss in expectation of life of patients with chronic
More informationKinetics of BCR-ABL Transcripts in Imatinib Mesylate treated Chronic Phase CML (CPCML), A Predictor of Response and Progression Free Survival
International journal of Biomedical science ORIGINAL ARTICLE Kinetics of BCR-ABL Transcripts in Imatinib Mesylate treated Chronic Phase CML (CPCML), A Predictor of Response and Progression Free Survival
More informationt(9;22)(q34;q11) as part of a single or complex translocation, or BCR-ABL transcripts must be present in every case
CHRONIC MYELOID LEUKAEMIA Diagnostic Criteria Chronic phase CML t(9;22)(q34;q11) as part of a single or complex translocation, or BCR-ABL transcripts must be present in every case Maximally cellular marrow
More informationAn update on imatinib mesylate therapy in chronic myeloid leukaemia patients in a teaching hospital in Malaysia
Singapore Med J 2012; 53(1) : 57 An update on imatinib mesylate therapy in chronic myeloid leukaemia patients in a teaching hospital in Malaysia Bee PC 1, MD, MMed, Gan GG 1, MBBS, FRCP, Tai YT 1, MBBS,
More informationCML EHA: what s new? Novità dall EHA >> [ Leucemia mieloide cronica ] Relatore: G. MARTINELLI. Borgo S. Luigi Monteriggioni (Siena) ottobre 2008
Novità dall EHA >> [ Leucemia mieloide cronica ] CML EHA: what s new? Relatore: G. MARTINELLI 27-28 ottobre 2008 Borgo S. Luigi Monteriggioni (Siena) Leucemia mieloide cronica - Copyright FSE 1 CML EHA:
More informationDiscontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: What s Stopping us from Stopping?
Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: What s Stopping us from Stopping? David Pham, PharmD PGY2 Hematology/Oncology Pharmacy Resident South Texas VA Health Care System
More informationpan-canadian Oncology Drug Review Final Clinical Guidance Report Bosutinib (Bosulif) for Chronic Myelogenous Leukemia April 21, 2015
pan-canadian Oncology Drug Review Final Clinical Guidance Report Bosutinib (Bosulif) for Chronic Myelogenous Leukemia April 21, 2015 DISCLAIMER Not a Substitute for Professional Advice This report is primarily
More informationThe legally binding text is the original French version
The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 14 March 2007 SPRYCEL 20 mg, film-coated tablet, blister (377 637-9) SPRYCEL 20 mg, film-coated tablet, bottle (377
More informationPersonalized Therapy for Acute Myeloid Leukemia. Patrick Stiff MD Loyola University Medical Center
Personalized Therapy for Acute Myeloid Leukemia Patrick Stiff MD Loyola University Medical Center 708-327-3216 Major groups of Mutations in AML Targets for AML: Is this Achievable? Chronic Myeloid Leukemia:
More informationClinical Significance of ABL Kinase Domain Mutation in Chronic Myeloid Leukemia under Imatinib Therapy.
Clinical Significance of ABL Kinase Domain Mutation in Chronic Myeloid Leukemia under Imatinib Therapy 1 Amr A.Ghannam, Abdou S. M. 2 and Mona Hatata 2 1 Department of Clinical Oncology, Tanta university
More information