Stroma-supported culture in 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 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.
Kumagai
M
M
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
Manabe
A
A
Pui
C H
CH
Behm
F G
FG
Raimondi
S C
SC
Hancock
M L
ML
Mahmoud
H
H
Crist
W M
WM
Campana
D
D
D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D002051:Burkitt Lymphoma / Q000628:therapy*; D002470:Cell Survival; D002648:Child; D046508:Culture Techniques / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D016896:Treatment Outcome