Flow cytometric chemosensitivity assay as a predictive tool of early clinical response in acute lymphoblastic leukemia

• Published in: Pediatric blood & cancer 2009-10, Vol.53 (4), p.543-550
• Main Authors: Galderisi, Faith, Stork, Linda, Li, Ju, Mori, Motomi, Mongoue-Tchokote, Solange, Huang, James
• Format: Article
• Language: English
• Subjects: Acute lymphatic leukemia; acute lymphoblastic leukemia; Adolescent; Adult; Asparaginase; Blast; Blood; Bone Marrow - pathology; Cancer; chemosensitivity assay; Child; Child, Preschool; childhood; Children; Data processing; Dexamethasone; Drug resistance; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor - methods; Female; Flow cytometry; Flow Cytometry - methods; Humans; in vitro drug resistance; Infant; Karyotyping; Lymphoblasts; Male; Pediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Prednisone; Recurrence; response to induction; Risk factors; Risk groups; Vincristine
• ISSN: 1545-5009; 1545-5017; 1545-5017
• DOI: 10.1002/pbc.22119

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.