Best Practice & Research Clinical Haematology
Volume 22, Issue 3 , Pages 343-353 , September 2009

Prognostic factors in chronic myeloid leukaemia

  • Juan Carlos Hernández-Boluda, MD (Doctor)

      Affiliations

    • Haematology and Medical Oncology Department, Hospital Clínico Universitario, Valencia, Spain
  • ,
  • Francisco Cervantes, MD (Doctor)

      Affiliations

    • Haematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain
    • Corresponding Author InformationCorresponding author. Tel.: +34 932275428; Fax: +34 932275484.

References 

  1. Minot G, Buckman T, Isaacs R. Chronic myelogenous leukemia. JAMA. 1924;82:1489–1494
  2. Hehlmann R, Heimpel H, Hasford J, et al. Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group. Blood. 1993;82:398–407
  3. Hehlmann R, Heimpel H, Hasford J, et al. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group. Blood. 1994;84:4064–4077
  4. The Italian cooperative study group on chronic myeloid leukemia. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med. 1994;330:820–825
  5. Allan NC, Richards SM, Shepherd PCA, et al. The UK medical research council's working parties for therapeutic trials in adult leukaemia. Lancet. 1995;345:1392–1397
  6. Chronic myeloid leukemia trialist' collaborative group. Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials. J Natl Cancer Inst. 1997;89:1616–1620
  7. Bonifazi F, De Vivo A, Rosti G, et al. Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders. Blood. 2001;98:3074–3081
  8. Guilhot F, Chastang C, Michallet M, et al. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French chronic myeloid leukemia study group. N Engl J Med. 1997;337:223–229
  9. Baccarani M, Rosti G, De Vivo A, et al. A randomized study of interferon-alpha versus interferon-alpha and low-dose arabinosyl cytosine in chronic myeloid leukemia. Blood. 2002;99:1527–1535
  10. Lee SJ. Chronic myelogenous leukaemia. Br J Haematol. 2000;111:993–1009
  11. Gratwohl A, Hermans J, Goldman JM, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic bone marrow transplantation. Lancet. 1998;352:1087–1092
  12. Robin M, Guardiola P, Devergie A, et al. A 10-year median follow-up study after allogeneic stem cell transplantation for chronic myeloid leukemia in chronic phase from HLA-identical sibling donors. Leukemia. 2005;19:1613–1620
  13. Grahtwohl 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). Haematologica. 2006;91:513–521
  14. Crawley C, Szydlo R, Lalancette M, et al. Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the chronic leukemia working party of the EBMT. Blood. 2005;106:2969–2976
  15. Hochhaus A, Druker B, Sawyers C, et al. Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-α treatment. Blood. 2008;111:1039–1043
  16. Palandri F, Iacobucci I, Martinelli G, et al. Long-term outcome of complete cytogenetic responders after imatinib 400mg in late chronic phase, Philadelphia-positive chronic myeloid leukemia: the GIMEMA Working Party on CML. J Clin Oncol. 2008;26:106–111
  17. O'Brien SG, Guilhot F, Larson RA, 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
  18. O'Brien SG, Guilhot F, Goldman JM, 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 in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with imatinib. Blood. 2008;112:[abstract 186]
  19. Tura S, Baccarani M, Corbelli G, et al. Staging of chronic myeloid leukemia. Br J Haematol. 1981;47:105–119
  20. Cervantes F, Rozman C. A multivariate analysis of prognostic factors in chronic myeloid leukemia. Blood. 1982;60:1298–1304
  21. Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in ‘good risk’ chronic granulocytic leukemia. Blood. 1984;63:789–799
  22. Sokal JE, Baccarani M, Tura S, et al. Prognostic discrimination among younger patients with chronic granulocytic leukemia: relevance to bone marrow transplantation. Blood. 1985;66:1352–1357
  23. Sokal JE, Gomez GA, Baccarani M, et al. Prognostic significance of additional cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia. Blood. 1988;72:294–298
  24. Hasford J, Pfirrmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst. 1998;90:850–858
  25. Sinclair PB, Nacheva EP, Leversha M, et al. Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood. 2000;95:738–743
  26. Huntly BJP, Reid AG, Bench AJ, et al. Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia. Blood. 2001;98:1732–1738
  27. Kolomietz E, Al-Maghrabi J, Brennan S, et al. Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic deletions and may lead to altered prognosis. Blood. 2001;97:3581–3588
  28. Kreil S, Pfirrmann M, Haferlach C, et al. Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia. Blood. 2007;110:1283–1290
  29. Hasford J, Pfirrmann M, Shepherd P, et al. The impact of the combination of baseline risk group and cytogenetic response on the survival of patients with chronic myeloid leukemia treated with interferon-α. Haematologica. 2005;90:335–340
  30. Hochhaus A, Reiter A, Saussele S, et al. Molecular heterogeneity in complete cytogenetic responders after interferon-alpha therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission. German CML Study Group and the UK MRC CML Study Group. Blood. 2000;95:62–66
  31. Kluin-Nelemans HC, Buck G, le Cessie S, et al. Randomized comparison of low-dose versus high-dose interferon-alfa in chronic myeloid leukemia: prospective collaboration of 3 joint trials by the MRC and HOVON groups. Blood. 2004;103:4408–4415
  32. Iacobucci I, Rosti G, Amabile M, et al. Comparison between patients with Philadelphia-positive chronic phase chronic myeloid leukemia who obtained a complete cytogenetic response within 1 year of imatinib therapy and those who achieved such a response after 12 months of treatment. J Clin Oncol. 2006;24:454–459
  33. Marin D, Marktel S, Bua M, et al. Prognostic factors for patients with chronic myeloid leukaemia in chronic phase treated with imatinib mesylate after failure of interferon alfa. Leukemia. 2003;17:1448–1453
  34. Cervantes F, Hernandez-Boluda JC, Steegmann JL, et al. Imatinib mesylate therapy of chronic phase chronic myeloid leukemia resistant or intolerant to interferon: results and prognostic factors for response and progression-free survival in 150 patients. Haematologica. 2003;88:1117–1122
  35. Sneed TB, Kantarjian HM, Talpaz M, et al. The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase. Cancer. 2004;100:116–121
  36. Kantarjian HM, Cortes JE, O'Brien S, et al. Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha. Blood. 2004;104:1979–1988
  37. Cortes J, Talpaz M, Giles F, et al. Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. Blood. 2003;101:3794–3800
  38. O'Dwyer ME, Mauro MJ, Blasdel C, et al. Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Blood. 2004;103:451–455
  39. Cortes J, Talpaz M, O'Brien S, et al. Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Cancer. 2003;98:1105–1113
  40. Rosti G, Iacobucci I, Bassi S, et al. Impact of age on the outcome of patients with chronic myeloid leukemia in late chronic phase: results of a phase II study of the GIMEMA CML working party. Haematologica. 2007;92:101–105
  41. 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;105:2281–2286
  42. Merx K, Müller 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 α. Leukemia. 2002;16:1579–1583
  43. Wang L, Pearson K, Ferguson JE, et al. The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia. Br J Haematol. 2003;120:990–999
  44. 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;99:1928–1937
  45. 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;99:3530–3539
  46. Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–2417
  47. Huntly BJP, 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;102:2205–2212
  48. Kim DH, Popradi G, Sriharsha L, et al. No significance of 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;113:772–781
  49. Castagnetti F, Marzocchi G, Luatti S, et al. Deletions of the derivative chromosome 9 do not influence response to imatinib of early chronic phase chronic myeloid leukemia patients. A GIMEMA working party analysis. Blood. 2006;108:[abstract 2112]
  50. Müller 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 α/araC. Leukemia. 2003;17:2392–2400
  51. Zheng C, Haak M, Brors B, et al. Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis. Leukemia. 2006;20:1028–1034
  52. Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA. 2006;103:2794–2799
  53. Frank O, Brors B, Fabarius A, et al. Gene expression signature of primary imatinib-resistant chronic myeloid leukemia patients. Leukemia. 2006;20:1400–1407
  54. Yong ASM, Szydlo RM, Goldman JM, et al. Molecular profiling of CD34+ cells identifies low expression of CD7, along with high expression of proteinase 3 or elastase, as predictors of longer survival in patients with CML. Blood. 2006;107:205–212
  55. Mohty M, Yong ASM, Szydlo RM, et al. The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia. Blood. 2007;110:380–383
  56. Mc Lean LA, Gathmann I, Capdeville R, et al. Pharmacogenomic analysis of cytogenetic response in chronic myeloid leukemia patients treated with imatinib. Clin Cancer Res. 2004;10:155–165
  57. Villuendas R, Steegmann JL, Pollan M, et al. Identification of genes involved in imatinib resistance in CML: a gene-expression profiling approach. Leukemia. 2006;20:1047–1054
  58. Crossman LC, Mori M, Hsieh YC, et al. In chronic myeloid leukemia white cells from cytogenetic responders and non-responders to imatinib have very similar gene expression signatures. Haematologica. 2005;90:459–464
  59. 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 patients with de novo CML. Blood. 2005;106:2520–2526
  60. White DL, Saunders V, Dang P, et al. OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood. 2006;108:697–704
  61. White DL, Saunders V, 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;110:4064–4072
  62. Mahon FX, Belloc F, Lagarde V, et al. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood. 2003;101:2368–2373
  63. Dulucq S, Bouchet S, Turcq B, et al. Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2008;112:2024–2027
  64. Kantarjian H, Talpaz M, O'Brien S, et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood. 2004;103:2873–2878
  65. Hughes TP, Branford S, White DL, et al. Impact of early dose intensity on cytogenetic and molecular responses in chronic-phase CML patients receiving 600mg/day of imatinib as initial therapy. Blood. 2008;112:3965–3973
  66. Cortes J, Baccarani M, Guilhot F, et al. A phase III, randomized, open-label study of 400mg versus 800mg of imatinib mesylate in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular endpoints: 1-year results of TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity) study. Blood. 2008;112:[abstract 335]
  67. de Lavallade H, Apperley JF, Khorashad JS. 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
  68. 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;349:1423–1432
  69. 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
  70. 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
  71. 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 at 72 mo: an analysis from the International Randomized Study of Interferon versus STI571 (IRIS) in patients with chronic phase chronic myeloid leukemia. Blood. 2008;112:[abstract 334]
  72. 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:[abstract 2113]
  73. 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;17:2401–2409
  74. Hughes T, Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukaemia. Blood Rev. 2006;20:29–41
  75. Press RD, Love Z, Tronnes AA, et al. BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients. Blood. 2006;107:4250–4256
  76. Cortes J, Talpaz M, O'Brien S, et al. Molecular response in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res. 2005;11:3425–3432
  77. Larson RA, Druker BJ, Guilhot F, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111:4022–4028
  78. 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;109:3496–3499
  79. Guilhot F, Hughes TP, Cortes J, et al. Imatinib pharmacokinetic exposure and its correlation with clinical outcome in patients with chronic-phase chronic myeloid leukemia for 400mg and 800mg daily doses (Tyrosine Kinase Dose Optimization Study [TOPS]). Blood. 2008;112:[abstract 447]
  80. White D, Saunders V, Grigg A, et al. Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockage and predict response in chronic myeloid leukemia. J Clin Oncol. 2007;25:4445–4451
  81. 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
  82. Kantarjian HM, Giles F, Gattermann N, et al. Nilotinib (formerly 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. 2007;110:3540–3546
  83. 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;112:516–518
  84. Milojkovic D, Bua M, Apperley 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:[abstract 332]

PII: S1521-6926(09)00021-8

doi: 10.1016/j.beha.2009.04.005

Best Practice & Research Clinical Haematology
Volume 22, Issue 3 , Pages 343-353 , September 2009