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. 1996 Feb 1;97(3):755–760. doi: 10.1172/JCI118474

Stroma-supported culture in childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome.

M Kumagai 1, A Manabe 1, C H Pui 1, F G Behm 1, S C Raimondi 1, M L Hancock 1, H Mahmoud 1, W M Crist 1, D Campana 1
PMCID: PMC507113  PMID: 8609232

Abstract

We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings of treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50 +/- 9% (SE) among patients with higher cell recoveries ( > 91%), and 94 +/- 6% among those with reduced cell recoveries (+/- 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia.

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Selected References

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