{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:34:48Z","timestamp":1791178488670,"version":"4.1.0"},"reference-count":52,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The remarkable progress made in the treatment of chronic myeloid leukemia (CML) over the past decade has been accompanied by steady improvements in our capacity to accurately and sensitively monitor response to therapy. After the initial target of therapy, complete cytogenetic response (CCR), is achieved, peripheral blood BCR-ABL transcript levels measured by real-time quantitative reverse transcriptase PCR (RQ-PCR) define the subsequent response targets, major and complete molecular response (MMR and CMR). The majority of patients on first-line imatinib therapy achieve a \u201csafe haven\u201d defined as a confirmed MMR, but 20% to 30% stop imatinib due to intolerance and\/or resistance. Many imatinib-resistant patients can be effectively treated with second generation tyrosine kinase inhibitors (TKIs), but the actual drug selected should be based on the resistance profile of each inhibitor, in addition to issues of tolerance and disease phase. The main purpose of monitoring response with cytogenetics and RQ-PCR is to identify patients likely to achieve better long-term outcome if they are switched early to second-line therapy, either another TKI or an allograft. Mutation screening is most valuable in cases of loss of response to imatinib or a second-line TKI, but there are other settings where a high yield of mutations may justify regular mutation screening.<\/jats:p>","DOI":"10.1182\/asheducation-2009.1.477","type":"journal-article","created":{"date-parts":[[2009,12,11]],"date-time":"2009-12-11T20:35:31Z","timestamp":1260563731000},"page":"477-487","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":43,"title":["Monitoring disease response to tyrosine kinase inhibitor therapy in CML"],"prefix":"10.1182","volume":"2009","author":[{"given":"Timothy P.","family":"Hughes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Branford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2019111702184637500_R1","doi-asserted-by":"crossref","unstructured":"Kantarjian H, Pasquini R, Hamerschlak N, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood. 2007;109:5143\u20135150.","DOI":"10.1182\/blood-2006-11-056028"},{"key":"2019111702184637500_R2","doi-asserted-by":"crossref","unstructured":"Jabbour E, Kantarjian HM, Jones D, et al. Imatinib mesylate dose escalation is associated with durable responses in patients with chronic myeloid leukemia after cytogenetic failure on standard-dose imatinib therapy. Blood. 2009;113:2154\u20132160.","DOI":"10.1182\/blood-2008-04-154344"},{"key":"2019111702184637500_R3","doi-asserted-by":"crossref","unstructured":"Kantarjian H, Schiffer C, Jones D, Cortes J. Monitoring the response and course of chronic myeloid leukemia in the modern era of BCR-ABL tyrosine kinase inhibitors: practical advice on the use and interpretation of monitoring methods. Blood. 2008;111:1774\u20131780.","DOI":"10.1182\/blood-2007-09-110189"},{"key":"2019111702184637500_R4","doi-asserted-by":"crossref","unstructured":"Baccarani M, Pane F, Saglio G. Monitoring treatment of chronic myeloid leukemia. Haematologica. 2008;93:161\u2013169.","DOI":"10.3324\/haematol.12588"},{"key":"2019111702184637500_R5","doi-asserted-by":"crossref","unstructured":"Hughes T, Branford S. Measuring minimal disease in chronic myeloid leukemia: fluorescence in situ hybridization and polymerase chain reaction. Clin Lymphoma Myeloma. 2009;9:S266\u2013S271.","DOI":"10.3816\/CLM.2009.s.022"},{"key":"2019111702184637500_R6","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":"2019111702184637500_R7","doi-asserted-by":"crossref","unstructured":"Branford S, Fletcher L, Cross NCP, et al. Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. Blood. 2008;112:3330\u20133338.","DOI":"10.1182\/blood-2008-04-150680"},{"key":"2019111702184637500_R8","doi-asserted-by":"crossref","unstructured":"Hochhaus A, O\u2019Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 2009;23:1054\u20131061.","DOI":"10.1038\/leu.2009.38"},{"key":"2019111702184637500_R9","doi-asserted-by":"crossref","unstructured":"Hughes TP, Branford S, White DL, et al. Impact of early dose intensity on cytogenetic and molecular responses in chronic-phase CML patients receiving 600 mg\/day of imatinib as initial therapy. Blood. 2008;112:3965\u20133973.","DOI":"10.1182\/blood-2008-06-161737"},{"key":"2019111702184637500_R10","doi-asserted-by":"crossref","unstructured":"Bumm T, Mu\u0308ller 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":"2019111702184637500_R11","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":"2019111702184637500_R12","doi-asserted-by":"crossref","unstructured":"Branford S, Rudzki Z, Harper A, 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;17:2401\u20132409.","DOI":"10.1038\/sj.leu.2403158"},{"key":"2019111702184637500_R13","doi-asserted-by":"crossref","unstructured":"Ross DM, Branford S, Moore S, Hughes TP. Limited clinical value of regular bone marrow cytogenetic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCR-ABL. Leukemia. 2006;20:664\u2013670.","DOI":"10.1038\/sj.leu.2404139"},{"key":"2019111702184637500_R14","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":"2019111702184637500_R15","doi-asserted-by":"crossref","unstructured":"Marin D, Milojkovic D, Olavarria E, et al. European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood. 2008;112:4437\u20134444.","DOI":"10.1182\/blood-2008-06-162388"},{"key":"2019111702184637500_R16","doi-asserted-by":"crossref","unstructured":"Hughes TP, Hochhaus A, Branford S, et al. Reduction of BCR-ABL transcript levels at 6, 12, and 18 months (mo) correlates with long-term outcomes on imatinib (IM) at 72 mo: an analysis from the International Randomized Study of Interferon versus STI571 (IRIS) in patients (pts) with chronic phase chronic myeloid leukemia (CML-CP) [abstract]. Blood2008;112:334.","DOI":"10.1182\/blood.V112.11.334.334"},{"key":"2019111702184637500_R17","doi-asserted-by":"crossref","unstructured":"Khorashad JS, de Lavallade H, Apperley JF, et al. Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression. J Clin Oncol. 2008; 2016: 4806\u20134813.","DOI":"10.1200\/JCO.2008.16.9953"},{"key":"2019111702184637500_R18","doi-asserted-by":"crossref","unstructured":"Ernst T, Hoffmann J, Erben P, et al. ABL single nucleotide polymorphisms may masquerade as BCR-ABL mutations associated with resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia. Haematologica. 2008;93:1389\u20131393.","DOI":"10.3324\/haematol.12964"},{"key":"2019111702184637500_R19","doi-asserted-by":"crossref","unstructured":"Branford S, Rudzki Z, Walsh S, 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;102:276\u2013283.","DOI":"10.1182\/blood-2002-09-2896"},{"key":"2019111702184637500_R20","doi-asserted-by":"crossref","unstructured":"Branford S, Lawrence R, Grigg A, et al. Long term follow up of patients with CML in chronic phase treated with first-line imatinib suggests that earlier achievement of a major molecular response leads to greater stability of response [abstract]. 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Mol Cancer Ther. 2008;7:3834\u20133841.","DOI":"10.1158\/1535-7163.MCT-08-0482"},{"key":"2019111702184637500_R24","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":"2019111702184637500_R25","doi-asserted-by":"crossref","unstructured":"Forrest DL, Trainor S, Brinkman RR, et al. Cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia are correlated with Sokal risk scores and duration of therapy but not trough imatinib plasma levels. Leukemia Res. 2009;33:271\u2013275.","DOI":"10.1016\/j.leukres.2008.07.015"},{"key":"2019111702184637500_R26","doi-asserted-by":"crossref","unstructured":"Larson RA, Druker BJ, Guilhot F, et al. 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