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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 543-550 |
| Number of pages | 8 |
| Journal | Pediatric Blood and Cancer |
| Volume | 53 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 2009 |
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Keywords
- Acute lymphoblastic leukemia
- Chemosensitivity assay
- Childhood
- Flow cytometry
- In vitro drug resistance
- Response to induction
ASJC Scopus subject areas
- Oncology
- Pediatrics, Perinatology, and Child Health
- Hematology
- Medicine(all)
Cite this
Flow cytometric chemosensitivity assay as a predictive tool of early clinical response in acute lymphoblastic leukemia. / Galderisi, Faith; Stork, Linda; Li, Ju; Mori, Motomi (Tomi); Mongoue-Tchokote, Solange; Huang, James.
In: Pediatric Blood and Cancer, Vol. 53, No. 4, 10.2009, p. 543-550.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Flow cytometric chemosensitivity assay as a predictive tool of early clinical response in acute lymphoblastic leukemia
AU - Galderisi, Faith
AU - Stork, Linda
AU - Li, Ju
AU - Mori, Motomi (Tomi)
AU - Mongoue-Tchokote, Solange
AU - Huang, James
PY - 2009/10
Y1 - 2009/10
N2 - 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.
AB - 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.
KW - Acute lymphoblastic leukemia
KW - Chemosensitivity assay
KW - Childhood
KW - Flow cytometry
KW - In vitro drug resistance
KW - Response to induction
UR - http://www.scopus.com/inward/record.url?scp=69849091837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69849091837&partnerID=8YFLogxK
U2 - 10.1002/pbc.22119
DO - 10.1002/pbc.22119
M3 - Article
C2 - 19499583
AN - SCOPUS:69849091837
VL - 53
SP - 543
EP - 550
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
SN - 1545-5009
IS - 4
ER -