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Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 62-66
Molecular heterogeneity in complete cytogenetic responders after
interferon- therapy for chronic myelogenous leukemia: low levels of
minimal residual disease are associated with continuing remission
Andreas Hochhaus,
Andreas Reiter,
Susanne Saußele, Anja Reichert,
Michael Emig,
Jaspal Kaeda,
Beate Schultheis,
Ute Berger,
Patricia
C. A. Shepherd,
Norman C. Allan,
Rüdiger Hehlmann,
John M. Goldman, and
Nicholas C. P. Cross for the German CML Study Group and
the UK MRC CML Study Group
From the III. Medizinische Universitätsklinik, Fakultät
für Klinische Medizin, Mannheim der Universität Heidelberg,
Mannheim, Germany; Western General Hospital, Edinburgh, UK; Imperial
College School of Medicine, Hammersmith Hospital, Department of
Hematology, London, UK.
A substantial minority of patients with chronic myelogenous
leukemia (CML) achieve a complete response (CR) to treatment with interferon- (IFN), defined as the disappearance of Philadelphia chromosome-positive metaphases. Currently it is unclear how long IFN
treatment should be continued for such patients. We used a competitive
reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify
levels of BCR-ABL transcripts in 297 peripheral blood specimens
collected from 54 patients who had achieved CR with IFN. The median
duration of observation was 1.9 years (range, 0.3-11.0 years). Total
ABL transcripts were quantified as internal control and results were
expressed as the ratio BCR-ABL/ABL. All 54 patients had molecular
evidence of residual disease, although 3 patients were intermittently
PCR negative. The median BCR-ABL/ABL ratio at the time of maximal
response for each patient was 0.045% (range, 0%-3.6%). During the
period of observation 14 patients relapsed, 11 cytogenetically to
chronic phase disease and 3 directly to blastic phase. The median ratio
of BCR-ABL/ABL at maximal response was significantly higher in patients
who relapsed than in those who remained in CR (0.49% versus 0.021%,
P < 0.0001). Our findings show that the level of residual
disease falls with time in complete responders to IFN, but molecular
evidence of disease is rarely if ever eliminated. The actual level of
minimal residual disease correlates with the probability of relapse. We
suggest that for patients who reach CR, IFN should be continued at
least until relatively low levels of residual leukemia are achieved.
(Blood. 2000;95:62-66)
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92(11):
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8(3):
385 - 389.
[Abstract]
[Full Text]
[PDF]
|
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|
|
|
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108(1):
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[Full Text]
[PDF]
|
|
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|
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|
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12(10):
3037 - 3042.
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[Full Text]
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|
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|
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8(2):
231 - 239.
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[Full Text]
[PDF]
|
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|
|
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107(8):
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|
|
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17(3):
495 - 502.
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|
|
|
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|
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105(2):
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|
|
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104(7):
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|
|
|
|
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|
|
|
|
|
|
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103(6):
2284 - 2290.
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|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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83 - 86.
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[Full Text]
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|
|
|
|
|
|
|
R. Bhatia, M. Holtz, N. Niu, R. Gray, D. S. Snyder, C. L. Sawyers, D. A. Arber, M. L. Slovak, and S. J. Forman
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101(12):
4701 - 4707.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Nashed, K. W. Rao, and M. L. Gulley
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J. Mol. Diagn.,
May 1, 2003;
5(2):
63 - 72.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Sweeney, J. L. Frandsen, C. M. Verfaillie, and R. S. McIvor
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March 15, 2003;
63(6):
1304 - 1310.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Kantarjian, M. Talpaz, J. Cortes, S. O'Brien, S. Faderl, D. Thomas, F. Giles, M. B. Rios, J. Shan, and R. Arlinghaus
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January 1, 2003;
9(1):
160 - 166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. V. Melo, T. P. Hughes, and J. F. Apperley
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January 1, 2003;
2003(1):
132 - 152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Kantarjian, J. E. Cortes, S. O'Brien, F. Giles, G. Garcia-Manero, S. Faderl, D. Thomas, S. Jeha, M. B. Rios, L. Letvak, et al.
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January 1, 2003;
101(1):
97 - 100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Burchert, S. Wolfl, M. Schmidt, C. Brendel, B. Denecke, D. Cai, L. Odyvanova, T. Lahaye, M. C. Muller, T. Berg, et al.
Interferon-alpha , but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia
Blood,
January 1, 2003;
101(1):
259 - 264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. D. Kottaridis, R. E. Gale, S. E. Langabeer, M. E. Frew, D. T. Bowen, and D. C. Linch
Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors
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September 18, 2002;
100(7):
2393 - 2398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-I. Lee, H. Kantarjian, A. Glassman, M. Talpaz, and M.-S. Lee
Quantitative measurement of BCR/abl transcripts using real-time polymerase chain reaction
Ann. Onc.,
May 1, 2002;
13(5):
781 - 788.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Sweeney, M. D. Diers, J. L. Frandsen, R. Gunther, C. M. Verfaillie, and R. S. McIvor
Methotrexate Exacerbates Tumor Progression in a Murine Model of Chronic Myeloid Leukemia
J. Pharmacol. Exp. Ther.,
March 1, 2002;
300(3):
1075 - 1084.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bagg
Chronic Myeloid Leukemia: A Minimalistic View of Post-Therapeutic Monitoring
J. Mol. Diagn.,
February 1, 2002;
4(1):
1 - 10.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Bonifazi, A. de Vivo, G. Rosti, F. Guilhot, J. Guilhot, E. Trabacchi, R. Hehlmann, A. Hochhaus, P. C. A. Shepherd, J. L. Steegmann, et al.
Chronic myeloid leukemia and interferon-alpha : a study of complete cytogenetic responders
Blood,
November 15, 2001;
98(10):
3074 - 3081.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Goldman and B. J. Druker
Chronic myeloid leukemia: current treatment options
Blood,
October 1, 2001;
98(7):
2039 - 2042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kano, M. Akutsu, S. Tsunoda, H. Mano, Y. Sato, Y. Honma, and Y. Furukawa
In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents
Blood,
April 1, 2001;
97(7):
1999 - 2007.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Olavarria, E. Kanfer, R. Szydlo, J. Kaeda, K. Rezvani, K. Cwynarski, C. Pocock, F. Dazzi, C. Craddock, J. F. Apperley, 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,
March 15, 2001;
97(6):
1560 - 1565.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kantarjian, J. V. Melo, S. Tura, S. Giralt, and M. Talpaz
Chronic Myelogenous Leukemia: Disease Biology and Current and Future Therapeutic Strategies
Hematology,
January 1, 2000;
2000(1):
90 - 109.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
