title: Bone marrow stroma-supported culture of T-lineage acute lymphoblastic leukemic cells predicts treatment outcome in children: a Pediatric Oncology Group study.
abstract: Significant predictors of treatment outcome are poorly defined for patients with T-lineage acute lymphoblastic leukemia (T-ALL). A high WBC at diagnosis, which has traditionally been a predictor of poor response in T-ALL, has considerably weakened prognostic significance in the face of modern, more intensive chemotherapy. To test the hypothesis that bone marrow stroma-supported leukemic cell recovery might identify children at high risk for relapse, we measured the ex vivo recovery of T-ALL lymphoblasts from 29 newly diagnosed patients using a stromal cell co-culture assay. In all cases the T-ALL lymphoblasts showed an increase in recovery of T-ALL cells (RTC), ranging from 4 to 343%, in comparison to samples maintained without stroma. Since we were blinded to patient outcome in this case-control study, we then correlated patient outcome with RTC. The RTC for 18 patients in complete continuous remission (CCR) for greater than 4 years was stochastically larger than for the 11 patients who eventually relapsed (P = 0.011, by the two-sided Wilcoxon test). Furthermore, 100% of patients with an RTC of more than 26% had a CCR greater than 4 years while 78% of the patients with an RTC of less than 25% relapsed within 4 years. This is the first report to show that higher lymphoblast recovery may predict a more favorable outcome for children with T-ALL. A prospective study is needed to test whether stroma-supported leukemic cell recovery might serve as a basis for assigning risk-adjusted therapy.
authors.affiliation: University of New Mexico Health Sciences Center, Department of Pediatrics, Albuquerque, NM, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Winter
authors.forename: J
authors.initials: J
authors.lastname: Sweatman
authors.forename: J J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: M P
authors.initials: MP
authors.lastname: Link
authors.forename: M D
authors.initials: MD
authors.lastname: Amylon
authors.forename: J
authors.initials: J
authors.lastname: Pullen
authors.forename: B M
authors.initials: BM
authors.lastname: Camitta
authors.forename: R S
authors.initials: RS
authors.lastname: Larson
mesh_terms: D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D016022:Case-Control Studies; D002460:Cell Line; D019070:Cell Lineage; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques / Q000379:methods*; D006801:Humans; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D007958:Leukocyte Count; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D017154:Stromal Cells / Q000502:physiology*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured