Monitoring patients in complete cytogenetic remission after treatment of CML in chronic phase with imatinib: patterns of residual leukaemia and prognostic factors for cytogenetic relapse

被引:71
作者
Marin, D [1 ]
Kaeda, J [1 ]
Szydlo, R [1 ]
Saunders, S [1 ]
Fleming, A [1 ]
Howard, J [1 ]
Andreasson, C [1 ]
Bua, M [1 ]
Olavarria, E [1 ]
Rahemtulla, A [1 ]
Dazzi, F [1 ]
Kanfer, E [1 ]
Goldman, JM [1 ]
Apperley, JF [1 ]
机构
[1] Hammersmith Hosp, Imperial Coll, Dept Haematol, London W12 0NN, England
关键词
CML; imatinib; plateau; BCR-ABL transcripts; Q-PCR;
D O I
10.1038/sj.leu.2403664
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We monitored BCR-ABL transcript levels by quantitative real-time PCR in 103 patients treated with imatinib for chronic myeloid leukaemia in chronic phase for a median of 30.3 months ( range 5.5 - 49.9) after they achieved complete cytogenetic remission (CCyR). The patients could be divided into three groups: ( 1) in 32 patients transcript levels continued to decline during the period of observation ( nadir BCR - ABL/ABL ratio 0.015%); in five of these patients BCR - ABL transcripts became undetectable on repeated testing, ( 2) in 42 patients the transcript levels reached a plateau and ( 3) in 26 patients transcript numbers increased and the initial CCyR was lost. Three patients were not evaluable. Patients who remained in CCyR for at least 24 months appeared to have a low risk of subsequent cytogenetic relapse. We conclude that the pattern of 'residual' disease after achieving CCyR on imatinib is variable: some patients in CCyR show a progressive reduction in the level of residual disease, some reach a plateau where transcript numbers are relatively stable and others relapse with Ph-positive metaphases.
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收藏
页码:507 / 512
页数:6
相关论文
共 18 条
[1]  
AVERY S, 2004, LEUK RES S1, V28, P75
[2]   Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment [J].
Bhatia, R ;
Holtz, M ;
Niu, N ;
Gray, R ;
Snyder, DS ;
Sawyers, CL ;
Arber, DA ;
Slovak, ML ;
Forman, SJ .
BLOOD, 2003, 101 (12) :4701-4707
[3]  
BIERNAUX C, 1995, BLOOD, V86, P3118
[4]   Chronic myeloid leukemia and interferon-α:: a study of complete cytogenetic responders [J].
Bonifazi, F ;
de Vivo, A ;
Rosti, G ;
Guilhot, F ;
Guilhot, J ;
Trabacchi, E ;
Hehlmann, R ;
Hochhaus, A ;
Shepherd, PCA ;
Steegmann, JL ;
Kluin-Nelemans, HC ;
Thaler, J ;
Simonsson, B ;
Louwagie, A ;
Reiffers, J ;
Mahon, FX ;
Montefusco, E ;
Alimena, G ;
Hasford, J ;
Richards, S ;
Saglio, G ;
Testoni, N ;
Martinelli, G ;
Tura, S ;
Baccarani, M .
BLOOD, 2001, 98 (10) :3074-3081
[5]   The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: Biologic significance and implications for the assessment of minimal residual disease [J].
Bose, S ;
Deininger, M ;
Gora-Tybor, J ;
Goldman, JM ;
Melo, JV .
BLOOD, 1998, 92 (09) :3362-3367
[6]  
CROSS NCP, 1993, BLOOD, V82, P1929
[7]   Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia -: A Europe Against Cancer Program [J].
Gabert, J ;
Beillard, E ;
van der Velden, VHJ ;
Bi, W ;
Grimwade, D ;
Pallisgaard, N ;
Barbany, G ;
Cazzaniga, G ;
Cayuela, JM ;
Cavé, H ;
Pane, F ;
Aerts, JLE ;
De Micheli, D ;
Thirion, X ;
Pradel, V ;
González, M ;
Viehmann, S ;
Malec, M ;
Saglio, G ;
van Dongen, JJM .
LEUKEMIA, 2003, 17 (12) :2318-2357
[8]   Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro [J].
Graham, SM ;
Jorgensen, HG ;
Allan, E ;
Pearson, C ;
Alcorn, MJ ;
Richmond, L ;
Holyoake, TL .
BLOOD, 2002, 99 (01) :319-325
[9]   A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa [J].
Hasford, J ;
Pfirrmann, M ;
Hehlmann, R ;
Allan, NC ;
Baccarani, M ;
Kluin-Nelemans, JC ;
Alimena, G ;
Steegmann, JL ;
Ansari, H .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (11) :850-858
[10]   Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia [J].
Hughes, TP ;
Kaeda, J ;
Branford, S ;
Rudzki, Z ;
Hochhaus, A ;
Hensley, ML ;
Gathmann, I ;
Bolton, AE ;
van Hoomissen, IC ;
Goldman, JM ;
Radich, JP ;
Taylor, K ;
Durrant, S ;
Schwarer, A ;
Joske, D ;
Seymour, J ;
Grigg, A ;
Ma, D ;
Arthur, C ;
Bradstock, K ;
Joshua, D ;
Lechner, K ;
Verhoef, G ;
Louwagie, A ;
Martiat, P ;
Straetmans, N ;
Bosly, A ;
Shepherd, J ;
Shustik, C ;
Lipton, J ;
Kovacs, DM ;
Turner, AR ;
Nielsen, JL ;
Birgens, H ;
Bjerrum, OW ;
Guilhot, F ;
Reiffers, J ;
Rousselot, P ;
Facon, T ;
Harousseau, JL ;
Tulliez, M ;
Guerci, A ;
Blaise, D ;
Maloisel, F ;
Michallet, M ;
Fischer, T ;
Hossfeld, D ;
Mertelsmann, R ;
Andreesen, R ;
Nerl, C .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (15) :1423-1432