Abstract
Aim: To address the incidence and the prognostic role of a very early standard complete cytogenetic response (CCyR) or all Ph– metaphases (MET–, when <20 cells were evaluable). Methods: We revised 182 chronic phase chronic myelogenous leukemia patients treated with frontline imatinib (IM) at two institutions from June 2002 to June 2011. Results: After 3 months of treatment, 138 patients (75.8%) achieved CCyR/MET– while 44 patients (24.2%) still presented Ph+ metaphases (MET+) (<33%, 24 patients; ≥33%, 20 patients). On univariate analysis, palpable spleen enlargement (p < 0.001), WBC count >100.0 × 109/l at onset (p < 0.001), and male gender (p = 0.019) had a negative impact on achievement of CCyR/MET– at 3 months. Among patients with CCyR/MET– after 3 months, there were 15 failures (10.8%) compared to 21 (47.7%) among patients with MET+ (p < 0.001). The 5-year overall survival was 97.0% in patients CCyR/MET– at 3 months and 91.8% in patients MET+ at 3 months (p = 0.277); the 5-year progression-free survival was 88.2% in patients CCyR/MET– at 3 months and 48.4% in patients MET+ at 3 months (p < 0.001). Conclusions: The achievement of CCyR/MET– at 3 months seems to have prognostic relevance and could be a very early and useful indicator of an excellent response to IM beyond European LeukemiaNet guidelines.
Journal Section:
Editor's choice
References
1.
Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031–1037.
[PubMed]
2.
Hochhaus A, Druker B, Sawyers C, Guilhot F, Schiffer CA, Cortes J, Niederwieser DW, Gambacorti-Passerini C, Stone RM, Goldman J, Fischer T, O’Brien SG, Reiffers JJ, Mone M, Krahnke T, Talpaz M, Kantarjian HM: Favorable long-term follow-up results over six years for response, survival and safety with imatinib mesylate therapy in chronic phase chronic myeloid leukemia post failure of interferon-alpha treatment. Blood 2008;111:1039–1043.
[PubMed]
3.
O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ, IRIS Investigators: Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994–1004.
[PubMed]
4.
Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson RA, IRIS Investigators: Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006;355:2408–2417.
[PubMed]
5.
Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, Guilhot F, Porkka K, Ossenkoppele G, Lindoerfer D, Simonsson B, Pfirrmann M, Hehlmann R: Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 2011;118:686–692.
[PubMed]
6.
Tauchi T, Kizaki M, Okamoto S, Tanaka H, Tanimoto M, Inokuchi K, Murayama T, Saburi Y, Hino M, Tsudo M, Shimomura T, Isobe Y, Oshimi K, Dan K, Ohyashiki K, Ikeda Y, TARGET Investigators: Seven-year follow-up of patients receiving imatinib for the treatment of newly diagnosed chronic myelogenous leukemia by the TARGET system. Leuk Res 2011;35:585–590.
[PubMed]
7.
Hochhaus A, O’Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L, Goldman JM, Müller MC, Radich JP, Rudoltz M, Mone M, Gathmann I, Hughes TP, Larson RA, IRIS Investigators: Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009;23:1054–1061.
[PubMed]
8.
Marin D, Milojkovic D, Olavarria E, Khorashad JS, de Lavallade H, Reid AG, Foroni L, Rezvani K, Bua M, Dazzi F, Pavlu J, Klammer M, Kaeda JS, Goldman JM, Apperley JF: 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;112:4437–4444.
[PubMed]
9.
Kim DH, Sriharsha L, Jung CW, Kamel-Reid S, Radich JP, Lipton JH: Comprehensive evaluation of time-to-response parameter as a predictor of treatment failure following imatinib therapy in chronic phase chronic myeloid leukemia: which parameter at which time-point does matter? Am J Hematol 2010;85:856–862.
[PubMed]
10.
Jabbour E, Kantarjian H, O’Brien S, Shan J, Quintas-Cardama A, Faderl S, Garcia-Manero G, Ravandi F, Rios MB, Cortes J: The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Blood 2011 27;118:4541–4546.
11.
Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, Apperley J, Cervantes F, Cortes J, Deininger M, Gratwohl A, Guilhot F, Horowitz M, Hughes T, Kantarjian H, Larson R, Niederwieser D, Silver R, Hehlmann R, European LeukemiaNet: Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006;108:1809–1820.
[PubMed]
12.
Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, Nakamae H, Huguet F, Boqué C, Chuah C, Bleickardt E, Bradley-Garelik MB, Zhu C, Szatrowski T, Shapiro D, Baccarani M: Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid Leukemia. N Engl J Med 2010;362:2260–2270.
[PubMed]
13.
Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM, ENESTnd Investigators: Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251–2259.
[PubMed]
14.
Marin D, Ibrahim AR, Lucas C, Gerrard G, Wang L, Szydlo RM, Clark RE, Apperley JF, Milojkovic D, Bua M, Pavlu J, Paliompeis C, Reid A, Rezvani K, Goldman JM, Foroni L: Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol 2012;30:232–238.
[PubMed]
15.
Branford S, Fletcher L, Cross NC, Muller MC, Hochhaus A, Kim DW, Radich JP, Saglio G, Pane F, Kamel-Reid S, Wang YL, Press RD, Lynch K, Rudzki Z, Goldman JM, Hughes T: 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;112:3330–3338.
[PubMed]
16.
Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, Wang J, Kassack Ipiña JJ, Kim DW, Ogura M, Pavlovsky C, Junghanss C, Milone JH, Nicolini FE, Robak T, Van Droogenbroeck J, Vellenga E, Bradley-Garelik MB, Zhu C, Hochhaus A: Dasatinib or imatinib in newly diagnosed chronic phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 2012;119:1123–1129.
[PubMed]
17.
Kantarjian HM, Hochhaus A, Saglio G, De Souza C, Flinn IW, Stenke L, Goh YT, Rosti G, Nakamae H, Gallagher NJ, Hoenekopp A, Blakesley RE, Larson RA, Hughes TP: 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;12:841–851.
[PubMed]
© 2012 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2012
You do not currently have access to this content.
