Chronic myelogenous leukemia

JNCCN Journal of the National Comprehensive Cancer Network

Volumn 7, Issue 9, 2009, Pages 984-1023

  O'Brien, Susan ^a   Berman, Ellin ^b   Borghaei, Hossein ^c   DeAngelo, Daniel J ^d   Devetten, Marcel P ^e   Devine, Steven ^f   Erba, Harry P ^g   Gotlib, Jason ^h   Jagasia, Madan ⁱ   Moore, Joseph O ^j   Mughal, Tariq ^k   Pinilla Ibarz, Javier ^l   Radich, Jerald P ^m   Shah, Neil P ⁿ   Shami, Paul J ^o   Smith, B Douglas ^p   Snyder, David S ^q   Tallman, Martin S ^r   Talpaz, Moshe ^g   Wetzler, Meir ^s  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^c FOX CHASE CANCER CENTER   (United States)

^d Dana Farber/Brigham and Women's Cancer Center   (United States)

^e NEBRASKA MEDICAL CENTER   (United States)

^f OHIO STATE UNIVERSITY   (United States)

^g UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER   (United States)

^h STANFORD CANCER INSTITUTE   (United States)

ⁱ VANDERBILT INGRAM CANCER CENTER   (United States)

^j DUKE CANCER INSTITUTE   (United States)

^k UNIVERSITY OF TENNESSEE CANCER INSTITUTE   (United States)

^l H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^m SEATTLE CANCER CARE ALLIANCE   (United States)

ⁿ UNIVERSITY OF CALIFORNIA   (United States)

^o UNIVERSITY OF UTAH   (United States)

^p JOHNS HOPKINS UNIVERSITY   (United States)

^q CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^r NORTHWESTERN UNIVERSITY   (United States)

^s ROSWELL PARK CANCER INSTITUTE   (United States)

more..

Author keywords

Allogenic HSCT; Chronic myelogenous leukemia; Cytogenetic response; Dasatinib; Hematologic response; Imatinib; Karyotyping; NCCN Clinical Practice Guidelines; Nilotinib; Transplantation

Indexed keywords

APREPITANT; CARBAMAZEPINE; CLARITHROMYCIN; CYCLOSPORIN; DASATINIB; DEXAMETHASONE; ERYTHROMYCIN; IMATINIB; INTERFERON; ITRACONAZOLE; KETOCONAZOLE; NILOTINIB; PARACETAMOL; PHENOBARBITAL; PHENYTOIN; PIMOZIDE; RIFABUTIN; RIFAMPICIN; RIFAPENTINE; SIMVASTATIN; WARFARIN; ANTINEOPLASTIC AGENT;

ANEMIA; ASCITES; CANCER CHEMOTHERAPY; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; CYTOGENETICS; DEPRESSION; DIARRHEA; DISEASE COURSE; DRUG ANTAGONISM; EDEMA; FATIGUE; FOOD DRUG INTERACTION; GASTROINTESTINAL SYMPTOM; GENE TRANSLOCATION; GRAPEFRUIT JUICE; HEADACHE; HEMATOPOIETIC STEM CELL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; HYPERICUM PERFORATUM; LIVER TOXICITY; MUSCLE CRAMP; NAUSEA; NEUTROPENIA; PERICARDIAL EFFUSION; PHILADELPHIA 1 CHROMOSOME; PLEURA EFFUSION; QT PROLONGATION; RASH; REVIEW; THERAPY EFFECT; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; ARTICLE; PRACTICE GUIDELINE;

ANTINEOPLASTIC AGENTS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE;

EID: 72149087674     PISSN: 15401405     EISSN: 15401413     Source Type: Journal    
DOI: 10.6004/jnccn.2009.0065     Document Type: Review

References (183)

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-249.
2. Faderl SA, Talpaz M, Estrov Z, et al. The biology of chronic myeloid leukemia. N Engl J Med 1999;341:164-172.
3. Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci U S A 2006;103:2794-2799. (Pubitemid 43306628)
4. Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 2004;351:657-667.
5. Sawyers CL. Chronic myeloid leukemia. N Engl J Med 1999;340:1330-1340.
6. Stone RM. Optimizing treatment of chronic myeloid leukemia: a rational approach. Oncologist 2004;9:259-270. (Pubitemid 38756875)
7. Jabbour E, Cortes JE, Giles FJ, et al. Current and emerging treatment options in chronic myeloid leukemia. Cancer 2007;109:2171-2181. (Pubitemid 46801546)
8. Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002;346:645-652. (Pubitemid 34815868)
9. 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-alpha treatment. Blood 2008;111:1039-1043.
10. 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.
11. 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.
12. 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 (MMR) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CMLCP) treated with imatinib (IM) [abstract]. Blood 2008;112:Abstract 186.
13. Kantarjian HM, Talpaz M, O'Brien S, et al. Survival benefit with imatinib mesylate versus tnterferon-{alpha}-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia. Blood 2006;108:1835-1840.
14. Roy L, Guilhot J, Krahnke T, et al. Survival advantage from imatinib compared with the combination interferon-{alpha} plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials. Blood 2006;108:1478-1484. (Pubitemid 44316111)
15. Schiffer CA. BCR-ABL Tyrosine kinase inhibitors for chronic myelogenous leukemia. N Engl J Med 2007;357:258-265. (Pubitemid 47080390)
16. Berman E, Nicolaides M, Maki RG, et al. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med 2006;354:2006-2013.
17. Cortes J, O'Brien S, Quintas A, et al. Erythropoietin is effective in improving the anemia induced by imatinib mesylate therapy in patients with chronic myeloid leukemia in chronic phase. Cancer 2004;100:2396-2402. (Pubitemid 38657887)
18. Quintas-Cardama A, Kantarjian H, O'Brien S, et al. Granulocyte-colony- stimulating factor (filgrastim) may overcome imatinib-induced neutropenia in patients with chronic-phase chronic myelogenous leukemia. Cancer 2004;100:2592-2597. (Pubitemid 38715764)
19. Kerkela R, Grazette L, Yacobi R, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 2006;12:908-916. (Pubitemid 44175142)
20. Atallah E, Durand JB, Kantarjian H, Cortes J. Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood 2007;110:1233-1237. (Pubitemid 47281421)
21. Shah NP, Tran C, Lee FY, et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004;305:399-401. (Pubitemid 38938156)
22. Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib resistant Philadelphia chromosome-positive leukemias. N Eng J Med 2006;354:2531-2541. (Pubitemid 43882349)
23. 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. (Pubitemid 46425867)
24. Mauro MJ, Baccarani M, Cervantes F, et al. Dasatinib 2-year efficacy in patients with chronic-phase chronic myelogenous leukemia (CML-CP) with resistance or intolerance to imatinib (STARTC) [abstract]. J Clin Oncol 2008;26(Suppl 1):Abstract 7009.
25. 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) [abstract]. Blood 2008;112:Abstract 450.
26. 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;109:4143-4150. (Pubitemid 46743375)
27. Apperley JF, Cortes JE, Kim DW, et al. Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START A trial. J Clin Oncol 2009;27:3472-3479.
28. Kantarjian H, Cortes J, Kim DW, et al. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up. Blood 2009;113:6322-6329.
29. 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.
30. Cortes J, Kim DW, Raffoux E, et al. Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase. Leukemia 2008;22:2176-2183.
31. Saglio G, Kantarjian HM, Hochhaus A, et al. Dasatinib 140 mg once daily (QD) demonstrates equivalent efficacy and improved safety compared with 70 mg twice daily (BID) in patients with chronic myeloid leukemia in blast phase (CML-BP): 2-year data from CA180-035 [abstract]. Blood 2008;112:Abstract 3226.
32. Quintas-Cardama A, Han X, Kantarjian H, Cortes J. Tyrosine kinase inhibitor-induced platelet dysfunction in patients with chronic myeloid leukemia. Blood 2009;114:261-263.
33. Quintas-Cardama A, Kantarjian H, O'Brien S, et al. Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol 2007;25:3908-3914.
34. 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 2008;26:3204-3212.
35. Stone RM, Kim DW, Kantarjian HM, et al. Dasatinib dose-optimization study in chronic phase chronic myeloid leukemia (CML-CP): three-year follow-up with dasatinib 100 mg once daily and landmark analysis of cytogenetic response and progression-free survival (PFS) [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract 7007.
36. Cortes J, O'Brien S, Borthakur G, et al. Efficacy of dasatinib in patients (pts) with previously untreated chronic myelogenous leukemia (CML) in early chronic phase (CML-CP) [abstract]. Blood 2008;112:Abstract 182.
37. 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.
38. 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.
39. Kantarjian H, Giles F, Bhalla K, et al. Nilotinib in chronic myeloid leukemia patients in chronic phase (CML-CP) with imatinib (IM) resistance or intolerance: longer follow-up results of a phase II study [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract 7029.
40. 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;111:1834-1839.
41. Le Coutre PD, Giles F, Hochhaus A, et al. Nilotinib in chronic myeloid leukemia patients in accelerated phase (CML-AP) with imatinib (IM) resistance or intolerance: longer follow-up results of a phase II study [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract 7057.
42. Giles FJ, Larson RA, Kantarjian HM, et al. Nilotinib in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis (CML-BC) who are resistant or intolerant to imatinib (abstract). J Clin Oncol 2008;26(Suppl 1):Abstract 7017.
43. Martinelli G, Castagnetti F, Poerio A, et al. Molecular responses with nilotinib 800 mg daily as first-line treatment of chronic myeloid leukemia in chronic phase: results of a phase II trial of the GIMEMA CML WP [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract 7074.
44. Pye SM, Cortes J, Ault P, et al. The effects of imatinib on pregnancy outcome. Blood 2008;111:5505-5508.
45. Ault P, Kantarjian H, O'Brien S, et al. Pregnancy among patients with chronic myeloid leukemia treated with imatinib. J Clin Oncol 2006;24:1204-1208. (Pubitemid 46638819)
46. Heartin E, Walkinshaw S, Clark RE. Successful outcome of pregnancy in chronic myeloid leukemia treated with imatinib. Leuk Lymphoma 2004;45:1307-1308.
47. AlKindi S, Dennison D, Pathare A. Imatinib in pregnancy. Eur J Haematol 2005;74:535-537.
48. Ali R, Ozkalemkas F, Ozcelik T, et al. Pregnancy under treatment of imatinib and successful labor in a patient with chronic myelogenous leukemia (CML): outcome of discontinuation of imatinib therapy after achieving a molecular remission. Leuk Res 2005;29:971-973.
49. Prabhash K, Sastry PSRK, Biswas G, et al. Pregnancy outcome of two patients with imatinib. Ann Oncol 2005;16:1983-1984.
50. Choudhary DR, Mishra P, Kumar R, et al. Pregnancy on imatinib: fatal outcome with meningocele. Ann Oncol 2006;17:178-179.
51. Hensley ML, Ford JM. Imatinib treatment: specific issues related to safety, fertility, and pregnancy. Semin Hematol 2003;40(2 Suppl 2):21-25.
52. Seshadri T, Seymour JF, McArthur GA. Oligospermia in a patient receiving imatinib therapy for the hypereosinophilic syndrome. N EnglJ Med 2004;351:2134-2135. (Pubitemid 39482514)
53. Seymour JF, Grigg A, Reynolds J, et al. Two year data from a prospective safety study analyzing the consequences of imatinib mesylate inhibition of sensitive kinases other than bcr-abl in patients with previously untreated chronic phase CML [abstract]. Blood 2006;108:Abstract 2147.
54. Cortes J, O'Brien S, Ault P, et al. Pregnancy outcomes among patients with chronic myeloid leukemia treated with dasatinib [abstract]. Blood 2008;112:Abstract 3230.
55. Guo JQ, Wang JYG, Arlinghaus RB. Detection of BCR-ABL proteins in blood cells of benign phase chronic myelogenous leukemia patients. Cancer Res 1991;51:3048-3051.
56. Cortes J, Talpaz M, Beran M, et al. Philadelphia chromosome negative chronic myelogenous leukemia rearrangement of the breakpoint cluster region: long-term follow-up results. Cancer 1995;75:464-470.
57. Lipton JH, Khoroshko N, Golenkov A, et al. Phase II, randomized, multicenter, comparative study of peginterferon-alpha-2a (40 kD) (Pegasys) versus interferon alpha-2a (Roferon-A) in patients with treatment-naive, chronic-phase chronic myelogenous leukemia. Leuk Lymphoma 2007;48:497-505.
58. Michallet M, Maloisel F, Delain M, et al. Pegylated recombinant interferon alpha-2b vs recombinant interferon alpha-2b for the initial treatment of chronic-phase chronic myelogenous leukemia: a phase III study. Leukemia 2004;18:309-315.
59. Kantarjian HM, 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. (Pubitemid 38451654)
60. 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 [abstract]. Blood 2008;112:Abstract 335.
61. 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;112:3965-3973.
62. Aoki E, Kantarjian H, O'Brien S, et al. High-dose (HD) imatinib provides better responses in patients with untreated early chronic phase (CP) CML [abstract]. Blood 2006;108:Abstract 2143.
63. 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 2 trial of the GIMEMA CML Working Party. Blood 2009;113:3428-3434.
64. Baccarani M, Rosti G, Castagnetti F, et al. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia- positive chronic myeloid leukemia: a European LeukemiaNet Study. Blood 2009;113:4497-4504.
65. Gambacorti-Passerini C, Zucchetti M, Russo D, et al. Alpha1 acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients. Clin Cancer Res 2003;9:625-632. (Pubitemid 36182594)
66. 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. (Pubitemid 46572540)
67. 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.
68. Ault P, Kantarjian HM, Bryan J, et al. Clinical use of imatinib plasma levels in patients with chronic myeloid leukemia (CML) [abstract]. Blood 2008;112:Abstract 4255.
69. Thomas J, Wang L, Clark RE, Pirmohamed M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood 2004;104:3739-3745. (Pubitemid 39564452)
70. 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;110:4064-4072. (Pubitemid 350248463)
71. White DL, Saunders VA, Dang P, et al. CML patients with low OCT-1 activity achieve better molecular responses on high dose imatinib than on standard dose. Those with high OCT-1 activity have excellent responses on either dose: a TOPS correlative study [abstract]. Blood 2008;112:Abstract 3187.
72. Giannoudis A, Davies A, Lucas CM, et al. Effective dasatinib uptake may occur without human organic cation transporter 1 (hOCT1): implications for the treatment of imatinib-resistant chronic myeloid leukemia. Blood 2008;112:3348-3354.
73. White DL, Saunders VA, 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. (Pubitemid 44061372)
74. Nardi V, Azam M, Daley GQ. Mechanisms and implications of imatinib resistance mutations in BCR-ABL. Curr Opin Hematol 2004:11:35-43. (Pubitemid 38021719)
75. 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 resistant and mutation in the ATP phosphate-binding loop are associated with a poor prognosis. Blood 2003;102:276-283. (Pubitemid 36759665)
76. Soverini S, Martinelli G, Rosti G, et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol 2005;23:4100-4109. (Pubitemid 46211315)
77. Willis SG, Lange T, Demehri S, et al. High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naïve patients: correlation with clonal cytogenetic evolution but not response to therapy. Blood 2005;106:2128-2137.
78. le Coutre P, Tassi E, Varella-Garcia M, et al. Induction of resistance to the abelson inhibitor STI571 in human leukemic cells through gene amplification. Blood 2000;95:1758-1766.
79. Mahon FX, Deininger MW, Schultheis B, et al. Selection and characterization of BCR-ABL positive cells lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood 2000;96:1070-1079.
80. Weisberg E, Griffin JD. Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABL-transformed hematopoietic cell lines. Blood 2000;95:3498-3505
81. Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001;293:876-880.
82. Nicolini FE, Hayette S, Corm S, et al. Clinical outcome of 27 imatinib mesylate-resistant chronic myelogenous leukemia patients harboring a T315I BCR-ABL mutation. Haematologica 2007;92:1238-1241.
83. Nicolini FE, Corm S, Le QH, et al. Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP). Leukemia 2006;20:1061-1106.
84. Jabbour E, Kantarjian H, Jones D, et al. Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy. Blood 2008;112:53-55.
85. 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.
86. 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. (Pubitemid 44574988)
87. Hochhaus A, Kreil S, Corbin AS, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002;16:2190-2196.
88. Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol 2007;8:1018-1029.
89. Majlis A, Smith T, Talpaz M, et al. Significance of cytogenetic clonal evolution in chronic myelogenous leukemia. J Clin Oncol 1996;14:196-203. (Pubitemid 26020014)
90. O'Dwyer ME, Mauro MJ, Kurilik G, et al. The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML. Blood 2002;100:1628-1633. (Pubitemid 34925138)
91. Cortes JE, 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.
92. 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. (Pubitemid 38140072)
93. Terre C, Eclache V, Rousselot P, et al. Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia. Leukemia 2004;18:1340-1346.
94. Medina J, Kantarjian H, Talpaz M, et al. Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. Cancer 2003;98:1905-1911. (Pubitemid 37310233)
95. Feldman E, Najfeld V, Schuster M, et al. The emergence of Ph-, trisomy-8+ cells in patients with chronic myeloid leukemia treated with imatinib mesylate. Exp Hematol 2003;31:702-707. (Pubitemid 36945383)
96. 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;101:1941-1949. (Pubitemid 36237597)
97. 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;110:1509-1519. (Pubitemid 47463065)
98. 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;110:2991-2995. (Pubitemid 350006953)
99. Kantarjian HM, Talpaz M, O'Brien S, et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood 2003;101:473-475. (Pubitemid 36077567)
100. Marin D, Goldman JM, Olavarria E, Apperley JF. Transient benefit only from increasing the imatinib dose in CML patients who do not achieve complete cytogenetic remissions on conventional doses. Blood 2003;102:2702-2704. (Pubitemid 37193621)
101. Zonder JA, Pemberton P, Brandt H, et al. The effect of dose increase of imatinib mesylate in patients with chronic or accelerated phase chronic myelogenous leukemia with inadequate hematologic or cytogenetic response to initial treatment. Clin Cancer Res 2003;9:2092-2097.
102. 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;113:2154-2160.
103. Kantarjian HM, Larson RA, Guilhot F, et al. Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase. Cancer 2009;115:551-1260
104. 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;109:5143-5150. (Pubitemid 46890528)
105. Rousselot PH, Facon T, Paquette R, et al. Dasatinib or high-dose imatinib for patients with chronic myelogenous leukemia chronic-phase (CML-CP) resistant to standard-dose imatinib: 2-year follow-up data from START-R [abstract]. J Clin Oncol 2008;26(Suppl 1):Abstract 7012.
106. Quintas-Cardama A, Cortes J. Therapeutic options against BCR-ABL1 T315I-positive chronic myelogenous leukemia. Clin Cancer Res 2008;14:4392-4399.
107. Marin D, Kaeda JS, Andreasson C, et al. Phase I/II trial of adding semisynthetic homoharringtonine in chronic myeloid leukemia patients who have achieved partial or complete cytogenetic response on imatinib. Cancer 2005;103:1850-1855.
108. Quintas-Cardama A, Kantarjian H, Garcia-Manero G, et al. Phase I/II study of subcutaneous homoharringtonine in patients with chronic myeloid leukemia who have failed prior therapy. Cancer 2007;109:248-255.
109. Cortes JE, Khoury HJ, Corm S, et al. Subcutaneous omacetaxine mepesuccinate in imatinib-resistant chronic myeloid leukemia (CML) patients (Pts) with the T315I mutation: data from an ongoing phase II/III trial [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract 7008.
110. 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;111:1774-1780.
111. Muhlmann J, Thaler J, Hilbe W, et al. Fluorescent in situ hybridization (FISH) on peripheral blood smears for monitoring Philadelphia chromosome-positive chronic myeloid leukemia (CML) during interferon treatment: a new strategy for remission assessment. Genes Chromosomes Cancer 1998;21:90-100. (Pubitemid 28081234)
112. Landstrom A, Tefferi A. Fluorescent in situ hybridization in the diagnosis, prognosis, and treatment monitoring of chronic myeloid leukemia. Leuk Lymphoma 2006;47:397-402. (Pubitemid 43102086)
113. Douet-Guilbert N, Morel F, Le Charpentier T, et al. Interphase FISH for follow-up of Philadelphia chromosome-positive chronic myeloid leukemia treatment. Anticancer Res 2004;24:2535-2539. (Pubitemid 39166343)
114. Seong DC, Kantarjian HM, Ro JY, et al. Hypermetaphase fluorescence in situ hybridization for quantitative monitoring of Philadelphia chromosome-positive cells in patients with chronic myelogenous leukemia during treatment. Blood 1995;86:2343-2349.
115. Dewald GW, Wyatt WA, Juneau AL, et al. Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. Blood 1998;91:3357-3365.
116. 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;26:3358-3363.
117. Quintas-Cardama A, Cortes JE, O'Brien S, et al. Dasatinib early intervention after cytogenetic or hematologic resistance to imatinib in patients with chronic myeloid leukemia. Cancer 2009;115:2912-2921.
118. Kantarjian H, Talpaz M, Cortes J, et al. Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; gleevec) in chronic-phase chronic myelogenous leukemia. Clin Cancer Res 2003;9:160-166. (Pubitemid 36109728)
119. 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]. Blood 2008;112:Abstract 334.
120. 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 with CML. Blood 2006;107:4250-4256. (Pubitemid 43801348)
121. 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;13:6136-6143. (Pubitemid 350075073)
122. Cortes J, Talpaz M, O'Brien S, et al. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res 2005;11:3425-3432.
123. Iacobucci I, Saglio G, Rosti G, et al. Achieving a major molecular response at the time of a complete cytogenetic response predicts a better duration of CCgR in imatinib-treated chronic myeloid leukemia patients. Clin Cancer Res 2006;12:3037-3042. (Pubitemid 43837348)
124. 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.
125. 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. (Pubitemid 44394987)
126. 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;108:28-37. (Pubitemid 43990609)
127. Branford S, Cross NC, Hochhaus A, et al. Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia. Leukemia 2006;20:1925-1930. (Pubitemid 44614879)
128. Darkow T, Henk HJ, Thomas SK, et al. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 2007;25:481-496. (Pubitemid 46849189)
129. Noens L, van Lierde MA, De Bock R, et al. Prevalence, determinants, and outcomes of non-adherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood 2009;113:5401-5411.
130. 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) [abstract]. Blood 2008;112:Abstract 445.
131. 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;104:2926-2932. (Pubitemid 39434981)
132. Hochhaus A. Advances in the treatment of haematological malignancies: optimal sequence of CML treatment. Ann Oncol 2007;18(Suppl 9):ix58-3.
133. Quintas-Cardama A, Cortes JE. Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin Proc 2006;81:973-988. (Pubitemid 43993489)
134. Cortes J, O'Brien S, Kantarjian H. Discontinuation of imatinib therapy after achieving a molecular response. Blood 2004;104:2204-2205. (Pubitemid 39297882)
135. Rousselot P, Huguet F, Rea D, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 2007;109:58-60. (Pubitemid 46053043)
136. Mahon FX, Huguet F, Guilhot F, et al. Is it possible to stop imatinib in patients with chronic myeloid leukemia? An update from a French pilot study and first results from the multicentre «stop imatinib» (STIM) study [abstract]. Blood 2008;112:Abstract 187.
137. Ross DDM, Grigg A, Schwarer A, et al. The majority of chronic myeloid leukaemia patients who cease imatinib after achieving a sustained complete molecular response (CMR) remain in CMR1 and any relapses occur early [abstract]. Blood 2008;112:Abstract 1102.
138. 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.
139. Branford S, Lawrence R, Fletcher L, et al. The initial molecular response of chronic phase CML patients treated with second generation ABL inhibitor therapy after imatinib failure can predict inadequate response and provide indications for rational mutation screening [abstract]. Blood 2008;112:Abstract 331.
140. 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 [abstract]. Blood 2008; 112:Abstract 332.
141. Kantarjian HM, Deisseroth A, Kurzrock R, et al. Chronic myelogenous leukemia: a concise update. Blood 1993;82:691-703. (Pubitemid 23221645)
142. Savage DG, Szydlo RM, Chase A, et al. Bone marrow transplantation for chronic myeloid leukemia: the effects of differing criteria for defining chronic phase on probabilities of survival and relapse. Br J Haematol 1997;99:30-35. (Pubitemid 27461323)
143. Sokal JE, Baccarani M, Russo D, et al. Staging and prognosis in chronic myelogenous leukemia. Semin Hematol 1988;25:49-61.
144. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO classification of tumours of the haematopoietic and lymphoid tissues. IARC press: Lyon; 2008.
145. DeVita VT, Hellman S, Rosenburg SA, eds. Cancer: Principles and Practice of Oncology, 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.
146. Yanada M, Naoe T. Imatinib combined chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukemia: major challenges in current practice. Leuk Lymphoma 2006;47:1747-1753. (Pubitemid 44649756)
147. de Labarthe A, Rousselot P, Huguet-Rigal F, et al. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood 2007;109:1408-1413.
148. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 2004;103:4396-4407.
149. Thomas DA, Kantarjian HM, Cortes JE, et al. Outcome after frontline therapy with the hyper-CVAD and imatinib mesylate regimen for adults with de novo or minimally treated Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL) [abstract]. J Clin Oncol 2008;26(Suppl 1):Abstract 7019.
150. Ravandi F, Faderl S, Thomas DA, et al. Phase II study of combination of the hyperCVAD regimen with dasatinib in patients (pts) with newly diagnosed Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) [abstract]. J Clin Oncol 2008;26(Suppl 1):Abstract 7020.
151. Davies SM, DeFor TE, McGlave PB, et al. Equivalent outcomes in patients with chronic myelogenous leukemia after early transplantation of phenotypically matched bone marrow from related or unrelated donors. Am J Med 2001;110:339-346.
152. Hansen JA, Gooley TA, Martin PJ, et al. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N EnglJ Med 1998;338:962-968.
153. Horowitz MM, Rowlings PA, Passweg JR. Allogeneic bone marrow transplantation for CML: a report from the International Bone Marrow Transplant Registry. Bone Marrow Transplant 1996;17(Suppl 1):S5-6.
154. McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001;97:3390-3400.
155. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997;89:4531-4536.
156. Giralt S, Thall P, Khouri I, et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 2001;97:631-637.
157. Or R, Shapira M, Resnick I. Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase. Blood 2003;101:441-445.
158. Crawley C, Szyldo 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. (Pubitemid 41565887)
159. Goldman J, Szydlo R, Horowitz MM, et al. Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase. Blood 1993;82:2235-2238.
160. Beelen DW, Graeven U, Elmaagacli AH, et al. Prolonged administration of interferon-alpha in patients with chronic-phase Philadelphia chromosome-positive chronic myelogenous leukemia before allogeneic bone marrow transplantation may adversely affect transplant outcome. Blood 1995;85:2981-2990.
161. Morton AJ, Gooley T, Hansen JA, et al. Association between pretransplant interferon-alpha and outcome after unrelated donor marrow transplantation for chronic myelogenous leukemia in chronic phase. Blood 1998;92:394-401.
162. Anderlini P, Sheth S, Hicks K, et al. Re: imatinib mesylate administration in the first 100 days after stem cell transplantation. Biol Blood Marrow Transplant 2004;10:883-884.
163. Deininger M, Schleuning M, Greinix H, et al. The effect of prior exposure to imatinib on transplant-related mortality. Haematologica 2006;91:452-459.
164. Oehler VG, Gooley T, Snyder DS, et al. The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia. Blood 2007;109:1782-1789.
165. Lee SJ, Kukreja M, Wang T, et al. Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia. Blood 2008;112:3500-3507.
166. Jabbour E, Cortes J, Kantarjian H, et al. Novel tyrosine kinase inhibitor therapy before allogeneic stem cell transplantation in patients with chronic myeloid leukemia: no evidence for increased transplant-related toxicity. Cancer 2007;110:340-344.
167. le Coutre PD, Hemmati P, Neuburger S, et al. Allogeneic stem cell transplantation (SCT) in advanced chronic myeloid leukemia (CML) patients after tyrosine kinase inhibitor (TKI) therapy [abstract]. Blood 2008;112:Abstract 4419.
168. Breccia M, Palandri F, Iori AP, et al. Second-generation tyrosine kinase inhibitors before allogeneic stem cell transplantation in patients with chronic myeloid leukemia resistant to imatinib. Leuk Res 2009; in press.
169. Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European group for blood and marrow transplantation working party chronic leukemia. Blood 1995;86:2041-2050.
170. Luznik L, Fuchs EJ. Donor lymphocyte infusions to treat hematologic malignancies in relapse after allogeneic blood or marrow transplantation. Cancer Control 2002;9:123-137.
171. Gilleece MH, Dazzi F. Donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leuk Lymphoma 2003;44:23-28.
172. Simula MP, Marktel S, Fozza C, et al. Response to donor lymphocyte infusions for chronic myeloid leukemia is dose-dependent: the importance of escalating the cell dose to maximize therapeutic efficacy. Leukemia 2007;21:943-948.
173. Kantarjian HM, O'Brien S, Cortes JE, et al. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 2002;100:1590-1595. (Pubitemid 34925133)
174. Olavarria E, Ottmann OG, Deininger M, et al. Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia 2003;17:1707-1712.
175. Hess G, Bunjes D, Siegert W, et al. Sustained complete molecular remissions after treatment with imatinib-mesylate in patients with failure after allogeneic stem cell transplantation for chronic myelogenous leukemia: results of a prospective phase II open-label multicenter study. J Clin Oncol 2005;23:7583-7593.
176. Carpenter PA, Snyder DS, Flowers MED, et al. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood 2007;109:2791-2793.
177. DeAngelo DJ, Hochberg EP, Alyea EP, et al. Extended follow-up of patients treated with imatinib mesylate (Gleevec) for chronic myelogenous leukemia relapse after allogeneic transplantation: durable cytogenetic remission and conversion to complete donor chimerism without graft-versus-host disease. Clin Cancer Res 2004;10:5065-5071.
178. Weisser M, Tischer J, Schnittger S, et al. A comparison of donor lymphocyre infusions or imatinib mesylate for patients with chronic myelogenous leukemia who have relapsed after allogeneic stem cell transplantation. Haematologica 2006;91:663-666. (Pubitemid 43799465)
179. Porkka K, Koskenvesa P, Lundan T, et al. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood 2008;112:1005-1012.
180. Radich JP, Gehly G, Gooley T, et al. Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients. Blood 1995;85:2632-2638.
181. Radich JP, Gooley T, Bryant E, et al. The significance of bcr-abl molecular detection in chronic myeloid leukemia patients "late," 18 months or more after transplantation. Blood 2001;98:1701-1707.
182. Olavarria E, Kanfer E, Szydlo R, et al. Early detection of BCR-ABL transcripts by quantitative reverse transcriptase-polymerase chain reaction predicts outcome after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood 2001;97:1560-1565. (Pubitemid 32217216)
183. Mackinnon S, Barnett L, Heller G. Polymerase chain reaction is highly predictive of relapse in patients following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukemia. Bone Marrow Transplant 1996;17:643-647. (Pubitemid 26125720)