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Blood, 15 October 2000, Vol. 96, No. 8, pp. 2691-2696
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Clinical importance of minimal residual disease in childhood
acute lymphoblastic leukemia
Elaine Coustan-Smith,
Jose Sancho,
Michael L. Hancock,
James M. Boyett,
Frederick G. Behm,
Susana C. Raimondi,
John T. Sandlund,
Gaston K. Rivera,
Jeffrey E. Rubnitz,
Raul C. Ribeiro,
Ching-Hon Pui, and
Dario Campana
From the Departments of Hematology-Oncology,
Biostatistics and Epidemiology, and Pathology, St Jude Children's
Research Hospital, and University of Tennessee, Memphis, TN.
By using rapid flow cytometric techniques capable of
detecting one leukemic cell in 104 normal cells, we
prospectively studied minimal residual disease (MRD) in 195 children
with newly diagnosed acute lymphoblastic leukemia (ALL) in clinical
remission. Bone marrow aspirates (n = 629) were collected at the end
of remission induction therapy and at 3 intervals thereafter.
Detectable MRD (ie,  0.01% leukemic mononuclear cells) at each time
point was associated with a higher relapse rate
(P < .001); patients with high levels of MRD at the end
of the induction phase (1%) or at week 14 of continuation therapy
(0.1%) had a particularly poor outcome. The predictive strength of
MRD remained significant even after adjusting for adverse presenting
features, excluding patients at very high or very low risk of relapse
from the analysis, and considering levels of peripheral blood
lymphoblasts at day 7 and day 10 of induction therapy. The incidence of
relapse among patients with MRD at the end of the induction phase was
68% ± 16% (SE) if they remained with MRD through week 14 of
continuation therapy, compared with 7% ± 7% if MRD became
undetectable (P = .035). The persistence of MRD until
week 32 was highly predictive of relapse (all 4 MRD+
patients relapsed vs 2 of the 8 who converted to undetectable MRD
status; P = .021). Sequential monitoring of MRD by the
method described here provides highly significant, independent
prognostic information in children with ALL. Recent improvements in
this flow cytometric assay have made it applicable to more than 90% of
all new patients.
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113(18):
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|
|
|
|
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111(12):
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|
|
|
|
|
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111(6):
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|
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|
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|
|
|
|
|
|
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[Abstract]
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|
|
|
|
|
|
|
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1050 - 1057.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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July 1, 2006;
108(1):
97 - 102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K. Zehentner, W. Fritschle, T. Stelzer, K. M. Ghirardelli, K. Hunter, C. Wentzel, R. Bennington, C. L. Hansen, D. Myerson, M. Kalnoski, et al.
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430 - 437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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January 1, 2006;
23(1):
38 - 44.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. C. C. Rocha, C. Cheng, W. Liu, S. Kishi, S. Das, E. H. Cook, J. T. Sandlund, J. Rubnitz, R. Ribeiro, D. Campana, et al.
Pharmacogenetics of outcome in children with acute lymphoblastic leukemia
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June 15, 2005;
105(12):
4752 - 4758.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Stanulla, E. Schaeffeler, T. Flohr, G. Cario, A. Schrauder, M. Zimmermann, K. Welte, W.-D. Ludwig, C. R. Bartram, U. M. Zanger, et al.
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293(12):
1485 - 1489.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-H. Pui, M. Schrappe, R. C. Ribeiro, and C. M. Niemeyer
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January 1, 2004;
2004(1):
118 - 145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Li, J. Zhou, D. Zuckerman, M. Rue, V. Dalton, C. Lyons, L. B. Silverman, S. E. Sallan, and J. G. Gribben
Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse: implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection
Blood,
December 15, 2003;
102(13):
4520 - 4526.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-B. Vidriales, J. J. Perez, M. C. Lopez-Berges, N. Gutierrez, J. Ciudad, P. Lucio, L. Vazquez, R. Garcia-Sanz, M. C. del Canizo, J. Fernandez-Calvo, et al.
Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value
Blood,
June 15, 2003;
101(12):
4695 - 4700.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J Moppett, G A A Burke, C G Steward, A Oakhill, and N J Goulden
The clinical relevance of detection of minimal residual disease in childhood acute lymphoblastic leukaemia
J. Clin. Pathol.,
April 1, 2003;
56(4):
249 - 253.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. L. Carroll, D. Bhojwani, D.-J. Min, E. Raetz, M. Relling, S. Davies, J. R. Downing, C. L. Willman, and J. C. Reed
Pediatric Acute Lymphoblastic Leukemia
Hematology,
January 1, 2003;
2003(1):
102 - 131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Coustan-Smith, J. Sancho, M. L. Hancock, B. I. Razzouk, R. C. Ribeiro, G. K. Rivera, J. E. Rubnitz, J. T. Sandlund, C.-H. Pui, and D. Campana
Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia
Blood,
September 18, 2002;
100(7):
2399 - 2402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hotfilder, S. Rottgers, A. Rosemann, H. Jurgens, J. Harbott, and J. Vormoor
Immature CD34+CD19- progenitor/stem cells in TEL/AML1-positive acute lymphoblastic leukemia are genetically and functionally normal
Blood,
June 28, 2002;
100(2):
640 - 646.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia
Blood,
June 17, 2002;
100(1):
52 - 58.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. N. Dworzak, G. Froschl, D. Printz, G. Mann, U. Potschger, N. Muhlegger, G. Fritsch, and H. Gadner
Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia
Blood,
March 15, 2002;
99(6):
1952 - 1958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Nyvold, H. O. Madsen, L. P. Ryder, J. Seyfarth, A. Svejgaard, N. Clausen, F. Wesenberg, O. G. Jonsson, E. Forestier, and K. Schmiegelow
Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome
Blood,
February 15, 2002;
99(4):
1253 - 1258.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Hoelzer, N. Gokbuget, O. Ottmann, C.-H. Pui, M. V. Relling, F. R. Appelbaum, J. J.M. van Dongen, and T. Szczepanski
Acute Lymphoblastic Leukemia
Hematology,
January 1, 2002;
2002(1):
162 - 192.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Identification of novel markers for monitoring minimal residual disease in acute lymphoblastic leukemia
Blood,
April 1, 2001;
97(7):
2115 - 2120.
[Abstract]
[Full Text]
[PDF]
|
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|
|
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