Culture of Leukemic Lymphoblasts Predicts Treatment Outcome

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 to 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 6 9% (SE) among patients with higher cell recoveries ( . 91%), and 94 6 6% among those with reduced cell recoveries ( # 91%; P 5 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. ( J. Clin. Invest. 1996. 97:755–760.)