|
|
 Previous Article | Table of Contents | Next Article 
In vitro drug sensitivity testing can predict induction failure and early
relapse of childhood acute lymphoblastic leukemia
T Hongo, S Yajima, M Sakurai, Y Horikoshi and R Hanada
Department of Pediatrics, Hamamatsu University School of Medicine, Japan.
It is vital to develop effective therapy for children with acute
lymphoblastic leukemia (ALL), in whom no remission occurs or who suffer
relapse with current protocols. Cellular drug resistance is thought to be
an important cause of induction failure and relapse. We performed in vitro
tests of bone marrow samples in 196 children with newly diagnosed ALL with
a 4-day culture and a methyl-thiazol-tetrazolium assay. We tested 16 drugs
and calculated the 70% lethal dose (LD70) for 14 drugs and the leukemic
cell survival (LCS) rate for dexamethasone and prednisolone. For each
single drug, patients were classified into two groups, sensitive or
resistant, by median concentration of LD70 or LCS. When patients were
classified into three groups by sensitivity to four drugs of DPAV
(dexamethasone, prednisolone, L-asparaginase, and vincristine), 3-year
event-free survival (EFS; 95% confidence intervals) of the super sensitive
group (SS; sensitive to all 4 drugs) was 0.833 (0.690 to 0.976), that of
the intermediate sensitive group (IS; sensitive to 2 or 3 drugs) was 0.735
(0.609 to 0.863), and that of the relatively resistant group (RR; sensitive
to no drugs or to 1 drug) was 0.541 (0.411 to 0.670; P = .0008). We then
investigated the relationship between the above four-drug sensitivity and
the time of relapse. The SS and IS patients tended to maintain continuous
complete remission, and RR patients tended to undergo induction failure and
early and late relapse (P = .004). Initial white blood cell count,
immunologic classification, and age were also predictive factors, but the
patient numbers showed no statistical correlation between these factors and
the four-drug sensitivity groups (SS, IS, and RR). When we took three
groups SS/IS/RR and investigated the EFS for various clinical groups, DPAV
sensitivity strongly influenced EFS in the standard-risk ALL (P = .016). In
vitro drug sensitivity testing provides additional prognostic information
about childhood ALL, and early detection of drug resistance at the time
chemotherapy commences may provide a successful strategy for
individualizing treatment, as the results indicate de novo resistance to
front-line drugs and suggest alternative, second-line drugs.
Volume 89,
Issue 8,
pp. 2959-2965,
04/15/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Z. Ji, F. C. Mei, A. L. Miller, E. B. Thompson, and X. Cheng
Protein Kinase A (PKA) Isoform RII{beta} Mediates the Synergistic Killing Effect of cAMP and Glucocorticoid in Acute Lymphoblastic Leukemia Cells
J. Biol. Chem.,
August 8, 2008;
283(32):
21920 - 21925.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Laane, T. Panaretakis, K. Pokrovskaja, E. Buentke, M. Corcoran, S. Soderhall, M. Heyman, J. Mazur, B. Zhivotovsky, A. Porwit, et al.
Dexamethasone-induced apoptosis in acute lymphoblastic leukemia involves differential regulation of Bcl-2 family members
Haematologica,
November 1, 2007;
92(11):
1460 - 1469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. E. Tissing, M. L. den Boer, J. P. P. Meijerink, R. X. Menezes, S. Swagemakers, P. J. van der Spek, S. E. Sallan, S. A. Armstrong, and R. Pieters
Genomewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells
Blood,
May 1, 2007;
109(9):
3929 - 3935.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Irish, N. Anensen, R. Hovland, J. Skavland, A.-L. Borresen-Dale, O. Bruserud, G. P. Nolan, and B. T. Gjertsen
Flt3 Y591 duplication and Bcl-2 overexpression are detected in acute myeloid leukemia cells with high levels of phosphorylated wild-type p53
Blood,
March 15, 2007;
109(6):
2589 - 2596.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lamb, E. D. Crawford, D. Peck, J. W. Modell, I. C. Blat, M. J. Wrobel, J. Lerner, J.-P. Brunet, A. Subramanian, K. N. Ross, et al.
The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease.
Science,
September 29, 2006;
313(5795):
1929 - 1935.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. E. Tissing, J. P. P. Meijerink, B. Brinkhof, M. J. C. Broekhuis, R. X. Menezes, M. L. den Boer, and R. Pieters
Glucocorticoid-induced glucocorticoid-receptor expression and promoter usage is not linked to glucocorticoid resistance in childhood ALL
Blood,
August 1, 2006;
108(3):
1045 - 1049.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Feusner
Bcl-rambo: a maverick of apoptotic genes
Blood,
January 15, 2006;
107(2):
421 - 421.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Holleman, M. L. den Boer, R. X. de Menezes, M. H. Cheok, C. Cheng, K. M. Kazemier, G. E. Janka-Schaub, U. Gobel, U. B. Graubner, W. E. Evans, et al.
The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia
Blood,
January 15, 2006;
107(2):
769 - 776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Holleman, M. L. d. Boer, K. M. Kazemier, H. B. Beverloo, A. R. M. von Bergh, G. E. Janka-Schaub, and R. Pieters
Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia
Blood,
September 1, 2005;
106(5):
1817 - 1823.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J.E. Tissing, J. P.P. Meijerink, M. L. den Boer, B. Brinkhof, E. F.C. van Rossum, E. R. van Wering, J. W. Koper, P. Sonneveld, and R. Pieters
Genetic Variations in the Glucocorticoid Receptor Gene Are Not Related to Glucocorticoid Resistance in Childhood Acute Lymphoblastic Leukemia
Clin. Cancer Res.,
August 15, 2005;
11(16):
6050 - 6056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.L. Den Boer, D.O. Harms, R. Pieters, K.M. Kazemier, U. Gobel, D. Korholz, U. Graubner, R.J. Haas, N. Jorch, H.J. Spaar, et al.
Patient Stratification Based on Prednisolone-Vincristine-Asparaginase Resistance Profiles in Children With Acute Lymphoblastic Leukemia
J. Clin. Oncol.,
September 1, 2003;
21(17):
3262 - 3268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Zwaan, G. J. L. Kaspers, R. Pieters, K. Hahlen, D. R. Huismans, M. Zimmermann, J. Harbott, R. M. Slater, U. Creutzig, and A. J. P. Veerman
Cellular drug resistance in childhood acute myeloid leukemia is related to chromosomal abnormalities
Blood,
October 16, 2002;
100(9):
3352 - 3360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Zwaan, G. J. L. Kaspers, R. Pieters, K. Hahlen, G. E. Janka-Schaub, C. H. van Zantwijk, D. R. Huismans, E. de Vries, M. G. Rots, G. J. Peters, et al.
Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome
Blood,
January 1, 2002;
99(1):
245 - 251.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Zwaan, G.-J. L. Kaspers, R. Pieters, N. L. R.-V. Woerden, M. L. den Boer, R. Wunsche, M. M. A. Rottier, K. Hahlen, E. R. van Wering, G. E. Janka-Schaub, et al.
Cellular drug resistance profiles in childhood acute myeloid leukemia: differences between FAB types and comparison with acute lymphoblastic leukemia
Blood,
October 15, 2000;
96(8):
2879 - 2886.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. L. R.-v. Woerden, R. Pieters, A. H. Loonen, I. Hubeek, E. van Drunen, H. B. Beverloo, R. M. Slater, J. Harbott, J. Seyfarth, E. R. van Wering, et al.
TEL/AML1 gene fusion is related to in vitro drug sensitivity for L-asparaginase in childhood acute lymphoblastic leukemia
Blood,
August 1, 2000;
96(3):
1094 - 1099.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. Rots, R. Pieters, G.-J. L. Kaspers, C. H. van Zantwijk, P. Noordhuis, R. Mauritz, A. J.P. Veerman, G. Jansen, and G. J. Peters
Differential Methotrexate Resistance in Childhood T- Versus Common/PreB-Acute Lymphoblastic Leukemia Can Be Measured by an In Situ Thymidylate Synthase Inhibition Assay, But Not by the MTT Assay
Blood,
February 1, 1999;
93(3):
1067 - 1074.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Rubnitz and C.-H. Pui
Childhood Acute Lymphoblastic Leukemia
Oncologist,
December 1, 1997;
2(6):
374 - 380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
