title: Autonomous growth of blast cells is associated with reduced survival in acute myeloblastic leukemia.
abstract: We have previously classified the in vitro growth characteristics of clonogenic blasts from patients with acute myeloblastic leukemia (AML) according to their capacity to proliferate autonomously in a blast cell colony assay. Here we have analyzed whether the presence of in vitro autonomous growth characteristics has any clinical relevance in AML. We have studied 50 patients (age 2 to 64 years), all of whom were treated with combination chemotherapy, excluding patients with a history of antecedent myelodysplasia. Leukemic cells from 34 of 50 patients (68%) exhibited either partial or totally autonomous growth in a blast cell colony assay. Cells from the remaining patients exhibited nonautonomous growth and were either totally dependent on exogenous growth factor (n = 8) or failed to proliferate at all in the culture system used (n = 8). All 50 patients were treated by intensive chemotherapy and 69% achieved complete remission (CR). Patients whose blasts exhibited autonomous growth in vitro had a significantly lower CR rate (57%) compared with the 16 patients with nonautonomous growth (94%, P = .02). White blood cell count was the only other significant factor (P = .03), but in multivariate analysis growth characteristics remains the most important predictor of CR. Actuarial relapse risk is 80% and 42% at 5 years for autonomous and nonautonomous groups respectively (P = .1). Overall disease-free survival is 21.8% and is higher in the nonautonomous growth group at 54.2% compared with 11.3% at 5 years (P = .0015) in the autonomous growth characteristics was found to be the single most important indicator of CR and disease-free survival. Our data suggests that the suppression of autocrine growth factor production may be of value in the treatment of AML.
authors.affiliation: Department of Haematology, City Hospital, Nottingham, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Hunter
authors.forename: S Y
authors.initials: SY
authors.lastname: Rogers
authors.forename: I A
authors.initials: IA
authors.lastname: Roberts
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
authors.forename: N
authors.initials: N
authors.lastname: Russell
mesh_terms: D000293:Adolescent; D000328:Adult; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D011379:Prognosis; D012044:Regression Analysis; D016019:Survival Analysis; D014407:Tumor Cells, Cultured