STROMA-SUPPORTED CULTURE OF CHILDHOOD B-LINEAGE ACUTE LYMPHOBLASTIC-LEUKEMIA CELLS 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 cas es of newly diagnosed B-lineage acute lymphoblastic leukemia and relat ed the findings to treatment outcome in a single program of chemothera py. The numbers of leukemic cells recovered after 7 d of culture range d from < 1 to 292% (median, 91%). The basis of poor cell recoveries fr om stromal layers appeared to be a propensity of the lymphoblasts to u ndergo apoptosis. The probability of event-free survival at 4 yr of fo llow-up was 50+/-9% (SE) among patients with higher cell recoveries (> 91%), and 94+/-6% among those with reduced cell recoveries (less than or equal to 91%; P = 0.0003). The prognostic value of leukemic cell r ecovery 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 cell s 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.