Best Practice & Research Clinical Haematology
Volume 22, Issue 3 , Pages 331-341 , September 2009

Response definitions and European Leukemianet Management recommendations

References 

  1. O'Brien SG, Guilhot F, Larson R, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004
  2. Hughes TP, Kaeda J, Brandford S, et al. Frequency of major molecular response to imatinib or interferon alpha plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003;349:1421–1432
  3. 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;108:1809–1820
  4. Jabbour E, Cortes JE, Giles F, et al. Current and emerging treatment options in chronic myeloid leukemia. Cancer. 2007;109:2171–2181
  5. Hehlmann R, Hochhaus A. Baccarani M on behalf of the European LeukemiaNet. Chronic myeloid leukemia. Lancet. 2007;370:342–350
  6. Druker BJ. Translation of the Philadelphia chromosome into therapy for CML. Blood. 2008;112:4808–4815
  7. Talpaz M, Shah PS, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354:2531–2541
  8. Guilhot F, Apperley J, Kim DW, et al. Dasatinib induces significant hematologic and cytogenetic response in patients with imatinib-resistant or-intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007;109:4143–4150
  9. Cortes J, Rousselot P, Kim DW, et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood. 2007;109:3207–3213
  10. Hochhaus A, Kantarjian HM, Baccarani M, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007;109:2303–2309
  11. Hochhaus A, Baccarani M, Deininger M, et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia. 2008;22:1200–1206
  12. Shah NP, Kantarjian HM, Kim DW, et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib –resistant and intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2007;26:1–9
  13. Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354:2542–2551
  14. Kantarjian HM, Giles F, Gattermann N, et al. Nilotinib (AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2008;110:3540–3546
  15. Le Coutre P, Ottmann OG, Giles F, et al. Nilotinib (formerly AMN 107), a highly selective BCR-ABL tyrosine kinase inhibitor, is a active in patients with imatinib-resistant or-intolerant accelerated-phase chronic myelogenous leukemia. Blood. 2008;111:1834–1839
  16. Deininger MW. Nilotinib. Clin Cancer Res. 2008;14:4027–4031
  17. Reinhold U, Henning E, Leiblein S, et al. FISH for BCR-ABL on interphases of peripheral blood neutrophils but not of unselected white bone marrow cells in CML patients treated with imatinib. Leukemia. 2003;17:1925–1929
  18. Raanani P, Ben-Bassat I, Gan S, et al. Assessment of the response to imatinib in chronic myeloid leukemia patients: comparison between the FISH, multiplex and RT-PCR methods. Eur J Haematol. 2004;73:243–250
  19. Testoni N, Marzocchi G, Luatti S, et al. A prospective study in Ph+ chronic myeloid leukemia (CML) patients showing that interphase fluorescence-in-situ- hybridization (I-FISH) is effective as conventional cytogenetics for definition of cytogenetic response to imatinib. Correlation with molecular response (a GIMEMA CML WP study). Haematologica. in press.
  20. Hughes T, Deininger M, Hocchaus 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;108:28–37
  21. Saldanha J, Silvy M, Beaufils N, et al. Characterization of a reference material for BCR-ABL (M-BCR) mRNA quantitation by real-time amplification assays: towards new standards for gene expression measurements. Leukemia. 2007;21:1481–1487
  22. Müller MC, Erben P, Saglio G, et al. Harmonization of a BCR-ABL mRNA quantification using a uniform multifunctional control plasmid in 37 international laboratories. Leukemia. 2008;22:96–102
  23. 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;112:3330–3337
  24. Jones D, Kamel-Reid S, Bahler D, et al. Laboratory practice guidelines for detecting and reporting BCR-ABL drug resistance mutations in chronic myelogenous leukemia and acute lymphoblastic leukemia. J Mol Diagn. 2009;11:4–11
  25. Kantarjian HM, Talpaz M, O'Brien S, et al. Survival benefit with imatinib mesylate versus interferon-alpha-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia. Blood. 2006;108:1835–1840
  26. Druker BJ, Guilhot F, O'Brien SO, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–2417
  27. De Lavallade H, Apperley JF, Khorashad J, 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;26:3358–3363
  28. Hochhaus A, O'Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia, in press.
  29. O'Brien SG, Guilhot F, Goldman J, et al. International randomized study of interferon versus STI571 (IRIS) 7-year follow-up: sustained survival, low rate of transformation and increased rate of major molecular response (MMR) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib (IM). Blood. 2008;112(11):76;Abstract N. 186
  30. 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;112:4437–4444
  31. Roy L, Guilhot J, Krahnke T, et al. Survival advantage from imatinib compared with the combination interferon-alfa plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials. Blood. 2006;108:1478–1484
  32. Hughes T, Hochhaus A, Branford S, et al. Reduction of BCR-ABL transcript levels at 6, 12, and 18 months 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 with chronic phase chronic myeloid leukemia (CML-CP). Blood. 2008;112(11):129–130Abstract No. 334
  33. Hughes T, Branford S, While 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;112:3965–3972
  34. Müller MC, Hanfstein B, Erben P, et al. Molecular response to first line imatinib therapy is predictive for long term event free survival in patients with chronic phase chronic myelogenous leukemia – an interim analysis of the randomized German CML study IV. Blood. 2008;112(11):129;Abstract No. 333
  35. 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. Blood. 2008;112(11):735–736Abstract No. 2113
  36. 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(20):6136–6143
  37. Kantarjian H, O'Brien S, Shan J, et al. Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia. Cancer. 2008;112:837–845
  38. Kantarjian HM, Shan J, Jones D, et al. Significance of rising levels of minimal residual disease in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) in complete cytogenetic response (CGCR). Blood. 2008;112(11):169–170Abstract No. 445
  39. Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukemia. Lancet Oncol. 2007;8:1018–1029
  40. Apperley JF. Part II: management of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007;8:1116–1129
  41. Quintas-Cardama A, Cortes J. Molecular biology of BCR-ABL1-positive chronic myeloid leukemia. Blood. 2009;113:1619–1630
  42. O'Hare T, Eide CA, Deininger MWN. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood. 2007;110:2242–2249
  43. Soverini S, Colarossi S, Gnani A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA working party on chronic myeloid leukemia. Clin Cancer Res. 2006;12:7374–7379
  44. Jabbour E, Kantarjian H, Jones D, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia. 2006;20:1767–1773
  45. 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;26:4806–4813
  46. Soverini S, Colarossi S, Gnani A, et al. Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain. Haematologica. 2007;92:401–403
  47. Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood. 1984;63:789–799
  48. Hasford J, Pfirmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst. 1998;90:850–858
  49. Jabbour E, Kantarjian HM, Jones D, et al. Imatinib mesylate dose escalation is associated with durable response in patients with chronic myeloid leukemia after cytogenetic failure on standard-dose imatinib therapy. Blood. 2009;113:2154–2160
  50. Cortes I, Kantarjian H, Goldberg S, et al. High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: high rates of rapid cytogenetic and molecular responses. J Clin Oncol, in press.
  51. Castagnetti F, Palandri F, Amabile M, et al. Results of high-dose imatinib mesylate in intermediate Sokal risk chronic myeloid leukemia patients in early chronic phase: a phase II trial of the Gimema CML WP. Blood, in press.
  52. Cortes J, Baccarani M, Guilhot F, et al. A phase III, randomized, open-label study of 400 mg versus 800 mg of imatinib mesylate (IM) in patients (pts) with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP) using molecular endpoints: 1-year results of TOPS (tyrosine kinase inhibitor optimization and selectivity) study. Blood. 2008;112(11):130–131Abstract No. 325
  53. Baccarani M, Rosti G, Castagnetti F, et al. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of patients with high risk, Philadelphia-positive, chronic myeloid leukemia. A European LeukemiaNet study. Blood. 2009;113:4497–4504
  54. Guilhot F, Mahon FX, Guilhot J, et al. Randomized comparison of imatinib versus imatinib combination therapies in newly diagnosed chronic myeloid leukaemia (CML) patients in chronic phase (CP): first results of the phase III (SPIRIT) trial from the French CML Group (FI LMC). Blood. 2008;112(11):74;Abstract No. 183
  55. Hehlmann R, Saussele S, Lauseker M, et al. Randomized comparison of imatinib 400 mg vs. imatinib + IFN vs. imatinib + araC vs. imatinib after IFN vs. imatinib 800 mg: optimized treatment and survival. Designed first interim analysis of the German CML study IV. Blood. 2008;112(11):75;Abstract No. 184
  56. Burgess M, Skaggs BJ, Shah NP, et al. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. PNAS. 2005;102:3395–3400
  57. Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant BCR-ABL. Cancer Cell. 2005;7:129–141
  58. Golemovic M, Verstovsek S, Giles F, et al. AMN107, a novel aminopyrimidine inhibitor of BCR-ABL, has in vitro activity against imatinib-resistant chronic myeloid leukemia. Clin Cancer Res. 2005;11:4941–4947
  59. Shah N, Tran C, Lee FY, et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004;305:399–401
  60. Tokarski JS, Newitt JA, Chang CYJ, et al. The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutation. Cancer Res. 2006;66:5790–5797
  61. Baccarani M, Rosti G, Saglio G, et al. Dasatinib time to and durability of major and complete cytogenetic response (MCyR and CCyR) in patients with chronic myeloid leukemia in chronic phase (CML-CP). Blood. 2008;112(11):172;Abstract No. 450
  62. Hochhaus A, Müller M, Radich J, et al. Dasatinib-associated major molecular responses are rapidly achieved in patients with chronic myeloid leukemia in chronic phase (CML-CP) following resistance, suboptimal response, or intolerance on imatinib. Blood. 2008;112(11):400;Abstract No. 1095
  63. Kantarjian HM, Kim DW, Dorlhiac-Llacer P, et al. Dasatinib 140 mg once daily (QD) demonstrates equivalent efficacy and improved safety compared with 70 mg twice daily (BID) in patients with accelerated phase chronic myeloid leukemia (CML-AP): 2-year follow-up data from CA180-035. Blood. 2008;112(11):1106–1107Abstract No. 3224
  64. Hochhaus A, Müller MC, Radich J, et al. Dasatinib-associated major molecular responses in patients with chronic myeloid leukemia in chronic phase following imatinib failure: response dynamics and predictive value. Leukemia, in press.
  65. Tam CS, Kantarjian H, Garcia-Manero G, et al. Failure to achieve a major cytogenetic response by 12 months defines inadequate response in patients receiving nilotinib or dasatinib as second or subsequent line therapy for chronic myeloid leukemia. Blood. 2008;112:516–517
  66. Milojkovic D, Bua M, Apperly JF, et al. Prediction of cytogenetic response to second generation TKI therapy in CML chronic phase patients who have failed imatinib therapy and early identification of factors that influence survival. Blood. 2008;112(11):129;Abstract No. 332
  67. Shah NP, Nicoll JM, Nagar B, et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell. 2002;2:117–125
  68. Corbin AS, La Rosee P, Stoffregen EP, et al. Several BCR-ABL kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood. 2003;101:4611–4614
  69. Azam M, Latek RR, Daley GQ. Mechanisms of autoinhibition and STI571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell. 2003;112:831–843
  70. O'Hare T, Walters DK, Stoffregen EP, et al. In vitro activity oof BCR-ABL inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistance ABL kinase domain mutants. Cancer Cell. 2005;65:4500–4505
  71. Manley PW, Cowan-Jacob SW, Mestan J. Advances in the structural biology, design and clinical development of BCR-ABL kinase inhibitors for the treatment of chronic myeloid leukemia. Biophys Acta. 2005;1754:3–13
  72. Bradeen HA, Eide CA, O'Hare T, et al. Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations. Blood. 2006;108:2332–2338
  73. Ray A, Cowan-Jacob SW, Manley PW, et al. Indentification of BCR-ABL point mutations conferring resistance to the ABL kinase inhibitor AMN107 (nilotinib) by random mutagenesis study. Blood. 2007;109:5011–5015
  74. Redaelli S, Piazza R, Rostagno R, et al. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol. 2009;27:469–471
  75. Gratwohl A, Hermans J, Goldman JM, et al. Risk assessment for patients whith chronic myeloid leukaemia before allogeneic blood or marrow transplantation: cronic leukemia working party of the European group for blood and marrow transplantation. Lancet. 1998;352:1087–1092
  76. Gratwohl A, Brand R, Apperley J, et al. Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, long-term data and current results. An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). l Haematologica. 2006;91(4):513–521
  77. Saussele S, Lauseker M, Gratwohl A, et al. Allogeneic hematopoietic stem cell transplantation (HSCT) in the imatinib-era: high survival rate following allogeneic HSCT after imatinib failure: results of the German CML study IV. Blood. 2008;112(11):171;Abstract No. 448
  78. Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia. An update of concepts and management recommendations of European Leukemianet. J Clin Oncol., in press.
  79. Baccarani M, Pane F, Saglio G. Monitoring treatment of chronic myeloid leukemia. Haematologica. 2008;92:161–169

PII: S1521-6926(09)00071-1

doi: 10.1016/j.beha.2009.10.001

Best Practice & Research Clinical Haematology
Volume 22, Issue 3 , Pages 331-341 , September 2009

Article Tools