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Research Article
Flow cytometric chemosensitivity assay as a predictive tool of early clinical response in acute lymphoblastic leukemia
Article first published online: 4 JUN 2009
DOI: 10.1002/pbc.22119
Copyright © 2009 Wiley-Liss, Inc.
Additional Information
How to Cite
Galderisi, F., Stork, L., Li, J., Mori, M., Mongoue-Tchokote, S. and Huang, J. (2009), Flow cytometric chemosensitivity assay as a predictive tool of early clinical response in acute lymphoblastic leukemia. Pediatric Blood & Cancer, 53: 543–550. doi: 10.1002/pbc.22119
Publication History
- Issue published online: 18 AUG 2009
- Article first published online: 4 JUN 2009
- Manuscript Accepted: 24 APR 2009
- Manuscript Received: 5 NOV 2008
Funded by
- Oregon Clinical and Translational Research Institute (OCTRI). Grant Number: UL1 RR024140
- National Center for Research Resources (NCRR)
- National Institutes of Health (NIH)
- NIH Roadmap for Medical Research
- Abstract
- Article
- References
- Cited By
Keywords:
- acute lymphoblastic leukemia;
- chemosensitivity assay;
- childhood;
- flow cytometry;
- in vitro drug resistance;
- response to induction
Abstract
Background
Residual disease or rapidity of response to induction therapy is among the most powerful predictors of outcome in pediatric acute lymphoblastic leukemia (ALL).
Method
Utilizing a multiparameter flow cytometric chemosensitivity assay (FCCA), we studied the relationship between in vitro drug sensitivity of diagnostic leukemic blasts from 30 children with ALL and rapidity of response to induction therapy. We also analyzed the in vitro drug sensitivity of de novo leukemic blasts among various clinical subsets.
Results
Compared to rapid early responders (RERs), slow early responders (SERs) had a significantly greater in vitro drug resistance to dexamethasone (DEX; P = 0.04) and prednisone (P = 0.05). The studies with all other drugs showed a non-significant trend with the SER having a higher in vitro drug resistance compared to the RER. Risk group stratified analyses indicated that in vitro resistance to asparaginase (ASP), DEX, and vincristine (VCR) were each significantly related to having very high risk ALL. Additionally, a significantly higher in vitro drug resistance to ASP and VCR was associated with unfavorable lymphoblast genetics and ultimate relapse.
Conclusion
Our data indicate that this FCCA is a potentially simple and rapid method to detect inherent resistance to initial ALL therapy very early in induction, thus allowing for treatment modification shortly thereafter. Pediatr Blood Cancer 2009;53:543–550. © 2009 Wiley-Liss, Inc.