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Sections Chronic Myelogenous Leukemia (CML)
Overview
Presentation
DDx
Workup
Treatment
Guidelines
Medication
Questions & Answers
Media Gallery
Tables
References

Presentation

History

The clinical manifestations of chronic myelogenous leukemia (CML) are insidious. The disease is often discovered incidentally in the chronic phase, when an elevated white blood cell (WBC) count is revealed by a routine blood count or when an enlarged spleen is found on a general physical examination.

Nonspecific symptoms of fatigue and weight loss may occur long after the onset of the disease. Loss of energy and decreased exercise tolerance may occur during the chronic phase after several months.

Patients often have symptoms related to enlargement of the spleen, liver, or both. The large spleen may encroach on the stomach and cause early satiety and decreased food intake. Left upper quadrant abdominal pain described as "gripping" may occur from spleen infarction. The enlarged spleen may also be associated with a hypermetabolic state, fever, weight loss, and chronic fatigue. The enlarged liver may contribute to the patient's weight loss.

Some patients with CML have low-grade fever and excessive sweating related to hypermetabolism.

In some patients who present in the accelerated, or acute, leukemia phase of the disease (skipping the chronic phase), bleeding, petechiae, and ecchymoses may be the prominent symptoms. In these situations, fever is usually associated with infections. Bone pain and fever, as well as an increase in bone marrow fibrosis, are harbingers of the blast phase.

Physical Examination

Splenomegaly is the most common physical finding in patients with CML. In more than 50% of the patients with CML, the spleen extends more than 5 cm below the left costal margin at time of discovery.

The size of the spleen correlates with the peripheral blood granulocyte counts, with the largest spleens being observed in patients with high WBC counts. A very large spleen is usually a harbinger of the transformation into an acute blast crisis form of the disease.

Hepatomegaly also occurs, although less commonly than splenomegaly. Hepatomegaly is usually part of the extramedullary hematopoiesis occurring in the spleen.

Physical findings of leukostasis and hyperviscosity can occur in some patients, with extraordinary elevation of their WBC counts, exceeding 300,000-600,000 cells/μL. Upon funduscopy, the retina may show papilledema, venous obstruction, and hemorrhages.

The blast crisis is marked by an increase in the bone marrow or peripheral blood blast count or by the development of soft-tissue or skin leukemic infiltrates. Typical symptoms are due to increasing anemia, thrombocytopenia, basophilia, a rapidly enlarging spleen, and failure of the usual medications to control leukocytosis and splenomegaly.

Differential Diagnoses

PDQ Adult Treatment Editorial Board. Chronic Myelogenous Leukemia Treatment (PDQ®): Health Professional Version. March 21, 2023. [QxMD MEDLINE Link]. [Full Text].
Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring. Am J Hematol. 2022 Sep. 97 (9):1236-1256. [QxMD MEDLINE Link].
Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001 Apr 5. 344(14):1038-42. [QxMD MEDLINE Link]. [Full Text].
Kantarjian H, Sawyers C, Hochhaus A, et al, for the International STI571 CML Study Group. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002 Feb 28. 346(9):645-52. [QxMD MEDLINE Link]. [Full Text].
Merx K, Muller MC, Kreil S, et al. Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon alpha. Leukemia. 2002 Sep. 16(9):1579-83. [QxMD MEDLINE Link]. [Full Text].
Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002 Mar 15. 99(6):1928-37. [QxMD MEDLINE Link]. [Full Text].
Kantarjian HM, Cortes JE, O'Brien S, et al. Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. Blood. 2003 Jan 1. 101(1):97-100. [QxMD MEDLINE Link]. [Full Text].
Shah NP, Tran C, Lee FY, et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004 Jul 16. 305(5682):399-401. [QxMD MEDLINE Link].
Volpe G, Panuzzo C, Ulisciani S, Cilloni D. Imatinib resistance in CML. Cancer Lett. 2009 Feb 8. 274(1):1-9. [QxMD MEDLINE Link].
Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 1999 Jul 15. 341(3):164-72. [QxMD MEDLINE Link].
Cancer Facts & Figures 2023. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf. Accessed: June 2, 2023.
Cancer Stat Facts: Leukemia - Chronic Myeloid Leukemia (CML). National Cancer Institute Surveillance, Epidemiology, and End Results Program. Available at https://seer.cancer.gov/statfacts/html/cmyl.html. Accessed: June 2, 2023.
Druker BJ, et al; IRIS Investigators. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006 Dec 7. 355 (23):2408-17. [QxMD MEDLINE Link]. [Full Text].
Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010 Jun 17. 362(24):2251-9. [QxMD MEDLINE Link].
Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boqué C, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014 Jan 23. 123 (4):494-500. [QxMD MEDLINE Link]. [Full Text].
Tim H Brümmendorf, Jorge E. Cortes, Dragana Milojkovic, Carlo Gambacorti-Passerini, et al. . Bosutinib (BOS) Versus Imatinib for Newly Diagnosed Chronic Phase (CP) Chronic Myeloid Leukemia (CML): Final 5-Year Results from the Bfore Trial. Blood. 2020. 136; (Supplement 1):41-42. [Full Text].
Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012 Nov 29. 367(22):2075-88. [QxMD MEDLINE Link].
Hochhaus A, Réa D, Boquimpani C, et al. Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Leukemia. 2023 Mar. 37 (3):617-626. [QxMD MEDLINE Link]. [Full Text].
Dybko J, Jaźwiec B, Haus O, Urbaniak-Kujda D, Kapelko-Słowik K, Wróbel T, et al. The Hasford Score May Predict Molecular Response in Chronic Myeloid Leukemia Patients: A Single Institution Experience. Dis Markers. 2016. 2016:7531472. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020 Apr. 34 (4):966-984. [QxMD MEDLINE Link]. [Full Text].
Wang W, Cortes JE, Tang G, Khoury JD, Wang S, Bueso-Ramos CE, et al. Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood. 2016 Mar 22. [QxMD MEDLINE Link].
Hehlmann R, Voskanyan A, Lauseker M, et al. High-Risk Additional Chromosomal Abnormalities in CML Herald Death By Blast Crisis Already at Low Blast Levels. Blood. November 13, 2019. 134 suppl 1:666. [Full Text].
Gambacorti-Passerini C, Antolini L, Mahon FX, Guilhot F, Deininger M al et. Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J Natl Cancer Inst. 2011 Apr 6. 103(7):553-61. [QxMD MEDLINE Link].
Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, et al. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017 Mar 9. 376 (10):917-927. [QxMD MEDLINE Link].
Longo DL. Imatinib Changed Everything. N Engl J Med. 2017 Mar 9. 376 (10):982-983. [QxMD MEDLINE Link].
[Guideline] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Chronic Myeloid Leukemia. National Comprehensive Cancer Network. Available at https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Version 2.2023 — April 13, 2023; Accessed: June 2, 2023.
Barrett AJ, Ito S. The role of stem cell transplantation for chronic myelogenous leukemia in the 21st century. Blood. 2015 May 21. 125 (21):3230-5. [QxMD MEDLINE Link].
Lyman GH, Henk HJ. Association of Generic Imatinib Availability and Pricing With Trends in Tyrosine Kinase Inhibitor Use in Patients With Chronic Myelogenous Leukemia. JAMA Oncol. 2020 Dec 1. 6 (12):1969-1971. [QxMD MEDLINE Link]. [Full Text].
Kenzik KM, Bhatia R, Bhatia S. Expenditures for First- and Second-Generation Tyrosine Kinase Inhibitors Before and After Transition of Imatinib to Generic Status. JAMA Oncol. 2020 Apr 1. 6 (4):542-546. [QxMD MEDLINE Link].
Shih YT, Cortes JE, Kantarjian HM. Treatment value of second-generation BCR-ABL1 tyrosine kinase inhibitors compared with imatinib to achieve treatment-free remission in patients with chronic myeloid leukaemia: a modelling study. Lancet Haematol. 2019 Aug. 6 (8):e398-e408. [QxMD MEDLINE Link]. [Full Text].
Chen CT, Kesselheim AS. Journey of Generic Imatinib: A Case Study in Oncology Drug Pricing. J Oncol Pract. 2017 Jun. 13 (6):352-355. [QxMD MEDLINE Link]. [Full Text].
Erçalışkan A, Seyhan Erdoğan D, Eşkazan AE. Current evidence on the efficacy and safety of generic imatinib in CML and the impact of generics on health care costs. Blood Adv. 2021 Sep 14. 5 (17):3344-3353. [QxMD MEDLINE Link]. [Full Text].
Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001 Apr 5. 344(14):1031-7. [QxMD MEDLINE Link]. [Full Text].
Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. Am J Hematol. 2020 Jun. 95 (6):691-709. [QxMD MEDLINE Link].
Santos FP, Alvarado Y, Kantarjian H, Verma D, O'Brien S, Mattiuzzi G, et al. Long-term prognostic impact of the use of erythropoietic-stimulating agents in patients with chronic myeloid leukemia in chronic phase treated with imatinib. Cancer. 2011 Mar 1. 117(5):982-91. [QxMD MEDLINE Link].
Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood. 2002 May 15. 99(10):3530-9. [QxMD MEDLINE Link].
Tang M, Gonen M, Quintas-Cardama A, et al. Dynamics of chronic myeloid leukemia response to long-term targeted therapy reveal treatment effects on leukemic stem cells. Blood. 2011 Aug 11. 118(6):1622-31. [QxMD MEDLINE Link].
Ibrahim AR, Eliasson L, Apperley JF, Milojkovic D, Bua M, Szydlo R, et al. Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy. Blood. 2011 Apr 7. 117(14):3733-6. [QxMD MEDLINE Link].
Hochhaus A, Kreil S, Corbin AS, La Rosée P, Müller MC, Lahaye T, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia. 2002 Nov. 16(11):2190-6. [QxMD MEDLINE Link].
[Guideline] Hochhaus A, Saussele S, Rosti G, Mahon FX, Janssen JJWM, Hjorth-Hansen H, et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1. 29 (Suppl 4):iv261. [QxMD MEDLINE Link]. [Full Text].
Marcolino MS, Boersma E, Clementino NC, et al. Imatinib treatment duration is related to decreased estimated glomerular filtration rate in chronic myeloid leukemia patients. Ann Oncol. 2011 Sep. 22(9):2073-9. [QxMD MEDLINE Link].
Dasatinib. National Cancer Institute. Available at https://www.cancer.gov/about-cancer/treatment/drugs/dasatinib. September 1, 2022; Accessed: June 2, 2023.
Nilotinib. National Cancer Institute. Available at https://www.cancer.gov/about-cancer/treatment/drugs/nilotinib. December 30, 2020; Accessed: June 2, 2023.
Bosulif (bosutinib) [package insert]. New York, NY: Pfizer, Inc. June 2020. Available at [Full Text].
Hughes TP, Hochhaus A, Branford S, Müller MC, Kaeda JS, Foroni L, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood. 2010 Nov 11. 116(19):3758-65. [QxMD MEDLINE Link].
FDA. Sprycel (dasatinib): Drug Safety Communication – Risk of Pulmonary Arterial Hypertension. US Food and Drug Administration. Available at https://wayback.archive-it.org/7993/20170112165154/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm275176.htm. October 11, 2011; Accessed: June 2, 2023.
Sawyers CL. Even better kinase inhibitors for chronic myeloid leukemia. N Engl J Med. 2010 Jun 17. 362(24):2314-5. [QxMD MEDLINE Link].
Jabbour E, Kantarjian H, O'Brien S, Shan J, Garcia-Manero G, Wierda W, et al. Predictive factors for outcome and response in patients treated with second generation tyrosine kinase inhibitors for chronic myeloid leukemia in chronic phase post imatinib failure. Blood. 2010 Oct 28. [QxMD MEDLINE Link].
Verma D, Kantarjian H, Strom SS, et al. Malignancies occurring during therapy with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) and other hematologic malignancies. Blood. 2011 Oct 20. 118(16):4353-8. [QxMD MEDLINE Link].
Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010 Jun 17. 362(24):2260-70. [QxMD MEDLINE Link].
Cortes JE, Jones D, O'Brien S, Jabbour E, Ravandi F, Koller C, et al. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J Clin Oncol. 2010 Jan 20. 28(3):398-404. [QxMD MEDLINE Link]. [Full Text].
Shah NP, Rousselot P, Schiffer C, Rea D, Cortes JE, Milone J, et al. Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. Am J Hematol. 2016 Sep. 91 (9):869-74. [QxMD MEDLINE Link]. [Full Text].
Kantarjian HM, Hochhaus A, Saglio G, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011 Sep. 12(9):841-51. [QxMD MEDLINE Link].
Tasigna (nilotinib) [package insert]. East Hanover, New Jersey 07936: Novartis Pharmaceuticals Corporation. June 2020. Available at [Full Text].
Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, et al. Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol. 2017 Nov 1. JCO2017747162. [QxMD MEDLINE Link]. [Full Text].
FDA approves bosutinib for pediatric patients with chronic myelogenous leukemia. FDA. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-bosutinib-pediatric-patients-chronic-myelogenous-leukemia. September 26, 2023; Accessed: October 13, 2023.
Chustecka Z. FDA Approves Ponatinib for Rare Leukemias. Medscape Medical News. December 14, 2012. [Full Text].
Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013 Nov 7. 369 (19):1783-96. [QxMD MEDLINE Link].
FDA Drug Safety Communication. FDA asks manufacturer of the leukemia drug Iclusig (ponatinib) to suspend marketing and sales. US Food and Drug Administration. Available at https://wayback.archive-it.org/7993/20170722185758/https://www.fda.gov/Drugs/DrugSafety/ucm373040.htm. November 5 2013; Accessed: May 27, 2022.
FDA Drug Safety Communication: FDA requires multiple new safety measures for leukemia drug Iclusig; company expected to resume marketing. US Food and Drug Administration. Available at https://wayback.archive-it.org/7993/20170722185750/https://www.fda.gov/Drugs/DrugSafety/ucm379554.htm. December 20, 2013; Accessed: May 27, 2022.
Cortes J, Apperley J, Lomaia E, et al. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial. Blood. 2021 Nov 25. 138 (21):2042-2050. [QxMD MEDLINE Link]. [Full Text].
Cortes JE, Deininger MW, Lomaia E, et al. Three-Year Update from the Optic Trial: A Dose-Optimization Study of 3 Starting Doses of Ponatinib. Blood. November 15, 2022. 140 suppl 1:1495-1497. [Full Text].
Saussele S, Haverkamp W, Lang F, Koschmieder S, Kiani A, Jentsch-Ullrich K, et al. Ponatinib in the Treatment of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Leukemia: Recommendations of a German Expert Consensus Panel with Focus on Cardiovascular Management. Acta Haematol. 2020. 143 (3):217-231. [QxMD MEDLINE Link]. [Full Text].
Scemblix (asciminib) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals, Corp. October 2021. Available at [Full Text].
Gotlib J, Kiladjian JJ, Vannucchi A, Rambaldi A, Reiter A, Shomali W, et al. A Phase 2 Study of Pemigatinib (FIGHT-203; INCB054828) in Patients with Myeloid/Lymphoid Neoplasms (MLNs) with Fibroblast Growth Factor Receptor 1 (FGFR1) Rearrangement (MLN FGFR1). Blood. 2021 Nov 23(138(suppl 1): 385. Presented at the 64th American Society of Hematology Virtual Meeting 2021. [Full Text].
Synribo (omacetaxine) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. October, 2012. Available at [Full Text].
Simonsson B, Gedde-Dahl T, Markevarn B, et al. Combination of pegylated IFN-a2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood. 2011 Sep 22. 118(12):3228-35. [QxMD MEDLINE Link].
Moreb J, Johnson T, Kubilis P, Myers L, Oblon D, Miller A, et al. Improved survival of patients with chronic myelogenous leukemia undergoing allogeneic bone marrow transplantation. Am J Hematol. 1995 Dec. 50(4):304-6. [QxMD MEDLINE Link].
McGlave PB, Beatty P, Ash R, Hows JM. Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases. Blood. 1990 Apr 15. 75(8):1728-32. [QxMD MEDLINE Link].
Deininger M, Schleuning M, Greinix H, Sayer HG, Fischer T, Martinez J, et al. The effect of prior exposure to imatinib on transplant-related mortality. Haematologica. 2006 Apr. 91(4):452-9. [QxMD MEDLINE Link].
Lima L, Bernal-Mizrachi L, Saxe D, Mann KP, Tighiouart M, Arellano M, et al. Peripheral blood monitoring of chronic myeloid leukemia during treatment with imatinib, second-line agents, and beyond. Cancer. 2011 Mar 15. 117(6):1245-52. [QxMD MEDLINE Link].
Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006 Sep 15. 108 (6):1809-20. [QxMD MEDLINE Link]. [Full Text].
Branford S, Rudzki Z, Harper A, Grigg A, Taylor K, Durrant S, et al. Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Leukemia. 2003 Dec. 17 (12):2401-9. [QxMD MEDLINE Link].
Cortes J, Talpaz M, O'Brien S, Jones D, Luthra R, Shan J, et al. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res. 2005 May 1. 11 (9):3425-32. [QxMD MEDLINE Link]. [Full Text].
Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J, et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood. 2003 Jul 1. 102 (1):276-83. [QxMD MEDLINE Link]. [Full Text].
Press RD, Galderisi C, Yang R, Rempfer C, Willis SG, Mauro MJ, et al. A half-log increase in BCR-ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response. Clin Cancer Res. 2007 Oct 15. 13 (20):6136-43. [QxMD MEDLINE Link]. [Full Text].
Saglio G, Sharf G, Almeida A, Bogdanovic A, Bombaci F, Čugurović J, et al. Considerations for Treatment-free Remission in Patients With Chronic Myeloid Leukemia: A Joint Patient-Physician Perspective. Clin Lymphoma Myeloma Leuk. 2018 Jun. 18 (6):375-379. [QxMD MEDLINE Link]. [Full Text].
Sweet K, Oehler V. Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when is this a safe option to consider?. Hematology Am Soc Hematol Educ Program. 2013. 2013:184-8. [QxMD MEDLINE Link]. [Full Text].
Saussele S, et al; EURO-SKI investigators. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018 Jun. 19 (6):747-757. [QxMD MEDLINE Link].
Saxena K, Jabbour E, Issa G, Sasaki K, Ravandi F, Maiti A, et al. Impact of frontline treatment approach on outcomes of myeloid blast phase CML. J Hematol Oncol. 2021 Jun 15. 14 (1):94. [QxMD MEDLINE Link]. [Full Text].
Atallah E, Schiffer CA, Radich JP, et al. Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial. JAMA Oncol. 2021 Jan 1. 7 (1):42-50. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Chronic myelogenous leukemia. Blood film at 400X magnification demonstrates leukocytosis with the presence of precursor cells of the myeloid lineage. In addition, basophilia, eosinophilia, and thrombocytosis can be seen. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Chronic myelogenous leukemia. Blood film at 1000X magnification demonstrates the whole granulocytic lineage, including an eosinophil and a basophil. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Chronic myelogenous leukemia. Blood film at 1000X magnification shows a promyelocyte, an eosinophil, and 3 basophils. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Chronic myelogenous leukemia. Bone marrow film at 400X magnification demonstrates clear dominance of granulopoiesis. The number of eosinophils and megakaryocytes is increased. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
The Philadelphia chromosome, which is a diagnostic karyotypic abnormality for chronic myelogenous leukemia, is shown in this picture of the banded chromosomes 9 and 22. Shown is the result of the reciprocal translocation of 22q to the lower arm of 9 and 9q (c-abl to a specific breakpoint cluster region [bcr] of chromosome 22 indicated by the arrows). Courtesy of Peter C. Nowell, MD, Department of Pathology and Clinical Laboratory of the University of Pennsylvania School of Medicine.
Chronic myelogenous leukemia. Fluorescence in situ hybridization using unique-sequence, double-fusion DNA probes for bcr (22q11.2) in red and c-abl (9q34) gene regions in green. The abnormal bcr/abl fusion present in Philadelphia chromosome–positive cells is in yellow (right panel) compared with a control (left panel). Courtesy of Emmanuel C. Besa, MD.

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Author

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Sara J Grethlein, MD, MBA, FACP Executive Medical Director and Medical Oncologist, Swedish Cancer Institute

Sara J Grethlein, MD, MBA, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Women's Association, American Society of Clinical Oncology, American Society of Hematology, Gold Humanism Honor Society, Leukemia and Lymphoma Society

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Acknowledgements

Bruce Buehler, MD Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Maurie Markman, MD Vice President for Medical Oncology Services, National Director for Medical Oncology, Cancer Treatment Centers of America

Maurie Markman, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Eli Lilly Honoraria Speaking and teaching; Genentech Consulting fee Consulting; Cellgene Consulting fee Consulting; Hana Pharmaceuticals Consulting fee Consulting; Boehringer Ingelheim Consulting fee Consulting; Ortho Biotech Consulting fee Consulting; Morphotech Consulting; Amgen Consulting fee Consulting

Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Clarence Sarkodee-Adoo, MD Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Disclosure: Takeda Millenium Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Sections Chronic Myelogenous Leukemia (CML)
Overview
Presentation
DDx
Workup
Treatment
Guidelines
Medication
Questions & Answers
Media Gallery
Tables
References

Mutation	Tyrosine kinase inhibitor
T3151	Ponatinib
F317L/V/I/C, T315A	Nilotinib, bosutinib, or ponatinib
V299L	Nilotinib or ponatinib
Y253H, E255V/K, F359V/I/C	Dasatinib, bosutinib, or ponatinib

Chronic Myelogenous Leukemia (CML) Clinical Presentation

History

Physical Examination

References

Tables

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