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Bone marrow stroma-supported culture of T-lineage acute lymphoblastic leukemic cells predicts treatment outcome in children: a Pediatric Oncology Group study

Leukemia volume 16, pages 1121–1126 (2002)Cite this article

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.

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Acknowledgements

This work was supported in part by the American Cancer Society IRG-192, Bear Necessities Pediatric Cancer Foundation, and the New Mexico Children's Cancer Fund (SSW), NIH CA 29139 and CA 37379 (JJS), NIH CA15989 (JP), NIH U10 CA30969, NIH P01 CA34233 (MPL), NIH U10 CA33603 (MA), the American Cancer Society's RPG-00–0096–01-LBC and Hoops for Lymphoma in memory of Fred Hartman (RSL).

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Authors and Affiliations

  1. Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    SS Winter & J Sweatman

  2. Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    RS Larson

  3. Department of Statistics, University of Florida, Gainesville, FL, USA

    JJ Shuster

  4. Department of Pediatrics, Stanford University, Stanford, CA, USA

    MP Link & MD Amylon

  5. University of Mississippi Medical Center, Jackson, MS, USA

    J Pullen

  6. Division of Pediatric Hematology/Oncology, The Midwest Children's Cancer Center, Milwaukee, WI, USA

    BM Camitta

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Winter, S., Sweatman, J., Shuster, J. et al. Bone marrow stroma-supported culture of T-lineage acute lymphoblastic leukemic cells predicts treatment outcome in children: a Pediatric Oncology Group study. Leukemia 16, 1121–1126 (2002). https://doi.org/10.1038/sj.leu.2402469

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