LEUKEMIC-CELL GROWTH IN SCID MICE AS A PREDICTOR OF RELAPSE IN HIGH-RISK B-LINEAGE ACUTE LYMPHOBLASTIC-LEUKEMIA

Mice with severe combined immunodeficiency (SCID) provide a model syst em to examine the in vivo homing, engraftment, and growth patterns of normal and malignant human hematopoietic cells. The relation between l eukemic cell growth in this model and the treatment outcome in patient s from whom cells were derived has not been established. Leukemic cell s from 42 children with newly diagnosed high-risk B-lineage acute lymp hoblastic leukemia were inoculated intravenously into CB.17 SCID mice. Mice were killed at 12 weeks or when they became moribund as a result of disseminated leukemia. All mice were necropsied and subjected to a series of laboratory studies to assess their burden of human leukemic cells. Twenty-three patients whose leukemic cells caused histopatholo gically detectable leukemia in SCID mice had a significantly higher re lapse rate than the 19 patients whose leukemic cells did not (estimate d 5-year event-free survival: 29.5% v 94.7%; 95% confidence intervals, 11.2% to 50.7% v 68.1% to 99.2%; P < .0001 by log-rank test). The occ urrence of overt leukemia in SCID mice was was a highly significant pr edictor of patient relapse. The estimated instantaneous risk of relaps e for patients whose leukemic cells caused overt leukemia in SCID mice was 21.5-fold greater than that for the remaining patients. Thus, gro wth of human leukemic cells in SCID mice is a strong and independent p redictor of relapse in patients with newly diagnosed high-risk B-linea ge acute lymphoblastic leukemia. (C) 1995 by The American Society of H ematology.