{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:30:38Z","timestamp":1790487038404,"version":"4.1.0"},"reference-count":43,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Imatinib is the therapeutic standard for newly diagnosed patients with chronic myeloid leukemia (CML). Recent updates of the IRIS trial, a study of standard-dose imatinib in newly diagnosed chronic-phase patients treated with 400 mg imatinib daily, suggest a stabilization of progression-free survival curves at a high level, implying that the majority of patients will do well on standard therapy. However, some 20% to 30% of patients will fail on imatinib and require alternative therapies. Identification of those patients likely to fail would be desirable to allow for more intensive therapy up front. After a brief overview of the history of CML, this paper will review current recommendations for staging of CML patients at diagnosis. Next, the various tests used to monitor their response to imatinib will be discussed in the context of the currently accepted criteria for imatinib failure and suboptimal response. Last, approaches to identify high-risk patients at diagnosis will be addressed.<\/jats:p>","DOI":"10.1182\/asheducation-2008.1.419","type":"journal-article","created":{"date-parts":[[2008,12,11]],"date-time":"2008-12-11T15:12:58Z","timestamp":1229008378000},"page":"419-426","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":46,"title":["Milestones and Monitoring in Patients with CML Treated with Imatinib"],"prefix":"10.1182","volume":"2008","author":[{"given":"Michael W.","family":"Deininger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2019111709010074800_R1","doi-asserted-by":"crossref","unstructured":"Hochhaus A, Druker BJ, Larson R, et al. IRIS 6-year follow-up: sustained survival and declining annual rate of transformation in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib [abstract]. Blood.2007;110. Abstract #15.","DOI":"10.1182\/blood.V110.11.25.25"},{"key":"2019111709010074800_R2","doi-asserted-by":"crossref","unstructured":"de Lavallade H, Apperley JF, Khorashad JS, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008;26:3358\u20133363.","DOI":"10.1200\/JCO.2007.15.8154"},{"key":"2019111709010074800_R3","doi-asserted-by":"crossref","unstructured":"Huntly BJ, Guilhot F, Reid AG, et al. Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions. Blood. 2003;102:2205\u20132212.","DOI":"10.1182\/blood-2002-09-2763"},{"key":"2019111709010074800_R4","doi-asserted-by":"crossref","unstructured":"Quintas-Cardama A, Kantarjian H, Talpaz M, et al. Imatinib mesylate therapy may overcome the poor prognostic significance of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia. Blood. 2005;105:2281\u20132286.","DOI":"10.1182\/blood-2004-06-2208"},{"key":"2019111709010074800_R5","doi-asserted-by":"crossref","unstructured":"Kim DH, Popradi G, Sriharsha L, et al. No significance of derivative chromosome 9 deletion on the clearance kinetics of BCR\/ABL fusion transcripts, cytogenetic or molecular response, loss of response, or treatment failure to imatinib mesylate therapy for chronic myeloid leukemia. Cancer. 2008;113:772\u2013781.","DOI":"10.1002\/cncr.23607"},{"key":"2019111709010074800_R6","doi-asserted-by":"crossref","unstructured":"Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV. The presence of BCR-ABL fusion genes in leukocytes of normal individuals: implications for the assessment of minimal residual disease. Blood. 1998;92:3362\u20133367.","DOI":"10.1182\/blood.V92.9.3362"},{"key":"2019111709010074800_R7","doi-asserted-by":"crossref","unstructured":"Muller MC, Gattermann N, Lahaye T, et al. Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha\/ara-C. Leukemia. 2003;17:2392\u20132400.","DOI":"10.1038\/sj.leu.2403157"},{"key":"2019111709010074800_R8","doi-asserted-by":"crossref","unstructured":"Bumm T, Muller C, Al Ali HK, et al. Emergence of clonal cytogenetic abnormalities in Ph- cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority. Blood. 2003;101:1941\u20131949.","DOI":"10.1182\/blood-2002-07-2053"},{"key":"2019111709010074800_R9","doi-asserted-by":"crossref","unstructured":"Jabbour E, Kantarjian HM, Abruzzo LV, et al. Chromosomal abnormalities in Philadelphia chromosome negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood. 2007;110:2991\u20132995.","DOI":"10.1182\/blood-2007-01-070045"},{"key":"2019111709010074800_R10","doi-asserted-by":"crossref","unstructured":"Deininger MW, Cortes J, Paquette R, et al. The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells. Cancer. 2007;110:1509\u20131519.","DOI":"10.1002\/cncr.22936"},{"key":"2019111709010074800_R11","doi-asserted-by":"crossref","unstructured":"Le Gouill S, Talmant P, Milpied N, et al. Fluorescence in situ hybridization on peripheral-blood specimens is a reliable method to evaluate cytogenetic response in chronic myeloid leukemia. J Clin Oncol. 2000;18:1533\u20131538.","DOI":"10.1200\/JCO.2000.18.7.1533"},{"key":"2019111709010074800_R12","doi-asserted-by":"crossref","unstructured":"Reinhold U, Hennig E, Leiblein S, Niederwieser D, Deininger MW. FISH for BCR-ABL on interphases of peripheral blood neutrophils but not of unselected white cells correlates with bone marrow cytogenetics in CML patients treated with imatinib. Leukemia. 2003;17:1925\u20131929.","DOI":"10.1038\/sj.leu.2403077"},{"key":"2019111709010074800_R13","doi-asserted-by":"crossref","unstructured":"Lesser ML, Dewald GW, Sison CP, Silver RT. Correlation of three methods of measuring cytogenetic response in chronic myelocytic leukemia. Cancer Genet Cytogenet. 2002;137:79\u201384.","DOI":"10.1016\/S0165-4608(02)00558-7"},{"key":"2019111709010074800_R14","doi-asserted-by":"crossref","unstructured":"Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28\u201337.","DOI":"10.1182\/blood-2006-01-0092"},{"key":"2019111709010074800_R15","doi-asserted-by":"crossref","unstructured":"Hughes TP, Kaeda J, Branford S, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003;349:1423\u20131432.","DOI":"10.1056\/NEJMoa030513"},{"key":"2019111709010074800_R16","doi-asserted-by":"crossref","unstructured":"Press RD, Galderisi C, Yang R, 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;13:6136\u20136143.","DOI":"10.1158\/1078-0432.CCR-07-1112"},{"key":"2019111709010074800_R17","doi-asserted-by":"crossref","unstructured":"Sherbenou DW, Wong MJ, Humayun A, et al. Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib. Leukemia. 2007;21:489\u2013493.","DOI":"10.1038\/sj.leu.2404554"},{"key":"2019111709010074800_R18","doi-asserted-by":"crossref","unstructured":"Picard S, Titier K, Etienne G, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2007;109:3496\u20133499.","DOI":"10.1182\/blood-2006-07-036012"},{"key":"2019111709010074800_R19","doi-asserted-by":"crossref","unstructured":"Larson RA, Druker BJ, Guilhot FA, et al. Imatinib pharmaco-kinetics and its correlation with response and safety in chronic phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111:4022\u20134028.","DOI":"10.1182\/blood-2007-10-116475"},{"key":"2019111709010074800_R20","doi-asserted-by":"crossref","unstructured":"Blasdel C, Egorin MJ, Lagattuta TF, Druker BJ, Deininger MW. Therapeutic drug monitoring in CML patients on imatinib. Blood. 2007;110:1699\u20131701.","DOI":"10.1182\/blood-2007-03-079871"},{"key":"2019111709010074800_R21","doi-asserted-by":"crossref","unstructured":"Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia. Recommendations from an expert panel on behalf of the European Leukemianet. Blood. 2006;108:1809\u20131820.","DOI":"10.1182\/blood-2006-02-005686"},{"key":"2019111709010074800_R22","unstructured":"NCCN Practice Guidelines in Oncology - v.3.2008. http:\/\/www.nccn.org\/professionals\/physician_gls\/PDF\/cml.pdf."},{"key":"2019111709010074800_R23","unstructured":"Druker BJ, Gathmann I, Bolton A, Larson RA, et al. Probability and impact of obtaining a complete cytogenetic response to imatinib as initial therapy for chronic myeloid leukemia (CML) in chronic phase [abstract]. Blood.2003;102. Abstract #182."},{"key":"2019111709010074800_R24","doi-asserted-by":"crossref","unstructured":"Alvarado Y, Kantarjian H, Faderl S, et al. Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in long-term outcome for patients (Pts) with chronic phase (CP) chronic myeloid leukemia (CML) [abstract]. Blood.2007;110. Abstract #1932.","DOI":"10.1182\/blood.V110.11.1932.1932"},{"key":"2019111709010074800_R25","doi-asserted-by":"crossref","unstructured":"Branford S, Rudzki Z, Parkinson I, et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations. Blood. 2004;104:2926\u20132932.","DOI":"10.1182\/blood-2004-03-1134"},{"key":"2019111709010074800_R26","doi-asserted-by":"crossref","unstructured":"Talpaz M, Rousselot P, Kim D-W, et al. A phase II study of dasatinib in patients with chronic myeloid leukemia (CML) in myeloid blast crisis who are resistant or intolerant to imatinib: first results of the CA180006 \u2018START-B\u2019 study [abstract]. Blood.2006;106. Abstract #16.","DOI":"10.1182\/blood.V106.11.40.40"},{"key":"2019111709010074800_R27","doi-asserted-by":"crossref","unstructured":"Le Coutre P, Ottmann OG, Giles F, et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated phase chronic myelogenous leukemia. Blood. 2008;111:1834\u20131839.","DOI":"10.1182\/blood-2007-04-083196"},{"key":"2019111709010074800_R28","doi-asserted-by":"crossref","unstructured":"Guilhot F, Apperley J, Kim DW, et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007;109:4143\u20134150.","DOI":"10.1182\/blood-2006-09-046839"},{"key":"2019111709010074800_R29","doi-asserted-by":"crossref","unstructured":"O\u2019Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood. 2007;110:2242\u20132249.","DOI":"10.1182\/blood-2007-03-066936"},{"key":"2019111709010074800_R30","doi-asserted-by":"crossref","unstructured":"Guilhot F, Larson RA, O\u2019Brien SG, Gathmann I, Druker BJ. Time to complete cytogenetic response (CCyR) does not affect long-term outcomes for patients on imatinib therapy [abstract]. Blood.2007;110. Abstract #27.","DOI":"10.1182\/blood.V110.11.27.27"},{"key":"2019111709010074800_R31","doi-asserted-by":"crossref","unstructured":"Frank O, Brors B, Fabarius A, et al. Gene expression signature of primary imatinib-resistant chronic myeloid leukemia patients. Leukemia. 2006;20:1400\u20131407.","DOI":"10.1038\/sj.leu.2404270"},{"key":"2019111709010074800_R32","doi-asserted-by":"crossref","unstructured":"McLean LA, Gathmann I, Capdeville R, Polymeropoulos MH, Dressman M. Pharmacogenomic analysis of cytogenetic response in chronic myeloid leukemia patients treated with imatinib. Clin Cancer Res. 2004;10:155\u2013165.","DOI":"10.1158\/1078-0432.CCR-0784-3"},{"key":"2019111709010074800_R33","doi-asserted-by":"crossref","unstructured":"Villuendas R, Steegmann JL, Pollan M, et al. Identification of genes involved in imatinib resistance in CML: a gene-expression profiling approach. Leukemia. 2006;20:1047\u20131054.","DOI":"10.1038\/sj.leu.2404197"},{"key":"2019111709010074800_R34","doi-asserted-by":"crossref","unstructured":"McWeeney SK, Pemberton LC, Harrington CA, Druker BJ, Deininger MW. A transcriptomal profile for predicting complete cytogenetic response (CCR) in chronic phase CML patients treated with imatinib [abstract]. Blood.2007;110. Abstract #1007.","DOI":"10.1182\/blood.V110.11.1007.1007"},{"key":"2019111709010074800_R35","doi-asserted-by":"crossref","unstructured":"White DL, Saunders VA, Dang P, et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity. Higher doses of imatinib may overcome the negative impact of low OCT-1 Activity. Blood. 2007;110:4064\u20134072.","DOI":"10.1182\/blood-2007-06-093617"},{"key":"2019111709010074800_R36","doi-asserted-by":"crossref","unstructured":"Crossman LC, Druker BJ, Deininger MW, et al. hOCT 1 and resistance to imatinib. Blood2005;106:1133\u20131134.","DOI":"10.1182\/blood-2005-02-0694"},{"key":"2019111709010074800_R37","doi-asserted-by":"crossref","unstructured":"Wang L, Giannoudis A, Lane S, et al. Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia. Clin Pharmacol Ther. 2008;83:258\u2013264.","DOI":"10.1038\/sj.clpt.6100268"},{"key":"2019111709010074800_R38","doi-asserted-by":"crossref","unstructured":"Kim DH, Sriharsha L, Xu W, et al. Clinical relevance of a pharmacogenetic approach using multiple candidate gene polymorphisms to predict response and resistance to imatinib mesylate therapy in chronic myeloid leukemia [abstract]. Blood.2007;110. Abstract #737.","DOI":"10.1182\/blood.V110.11.737.737"},{"key":"2019111709010074800_R39","doi-asserted-by":"crossref","unstructured":"Dulucq S, Bouchet S, Turcq B. Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2008;112:2024\u20132027.","DOI":"10.1182\/blood-2008-03-147744"},{"key":"2019111709010074800_R40","doi-asserted-by":"crossref","unstructured":"White D, Saunders V, Lyons AB, et al. In-vitro sensitivity to imatinib-induced inhibition of ABL kinase activity is predictive of molecular response in de-novo CML patients. Blood. 2005;106:2520\u20132526.","DOI":"10.1182\/blood-2005-03-1103"},{"key":"2019111709010074800_R41","doi-asserted-by":"crossref","unstructured":"Schultheis B, Szydlo R, Mahon FX, Apperley JF, Melo JV. Analysis of total phosphotyrosine levels in CD34+ cells from CML patients to predict the response to imatinib mesylate treatment. Blood. 2005;105:4893\u20134894.","DOI":"10.1182\/blood-2005-01-0210"},{"key":"2019111709010074800_R42","doi-asserted-by":"crossref","unstructured":"Cilloni D, Messa F, Gottardi E, et al. Sensitivity to imatinib therapy may be predicted by testing Wilms tumor gene expression and colony growth after a short in vitro incubation. Cancer. 2004;101:979\u2013988.","DOI":"10.1002\/cncr.20457"},{"key":"2019111709010074800_R43","doi-asserted-by":"crossref","unstructured":"Lange T, Gunther C, Kohler T, et al. High levels of BAX, low levels of MRP-1, and high platelets are independent predictors of response to imatinib in myeloid blast crisis of CML. Blood. 2003;101:2152\u20132155.","DOI":"10.1182\/blood-2002-05-1366"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2008\/1\/419\/786472\/419_426ash.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2008\/1\/419\/786472\/419_426ash.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T17:28:19Z","timestamp":1589390899000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2008\/1\/419\/95816\/Milestones-and-Monitoring-in-Patients-with-CML"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/asheducation-2008.1.419","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"value":"1520-4391","type":"print"},{"value":"1520-4383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,1]]}}}