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Leukemic cell growth in SCID mice as a predictor of relapse in high- risk
B-lineage acute lymphoblastic leukemia
FM Uckun, H Sather, G Reaman, J Shuster, V Land, M Trigg, R Gunther, L Chelstrom, A Bleyer and P Gaynon
University of Minnesota Biotherapy Program, the Department of Therapeutic
Radiology, Minneapolis.
Mice with severe combined immunodeficiency (SCID) provide a model system to
examine the in vivo homing, engraftment, and growth patterns of normal and
malignant human hematopoietic cells. The relation between leukemic cell
growth in this model and the treatment outcome in patients from whom cells
were derived has not been established. Leukemic cells from 42 children with
newly diagnosed high-risk B- lineage acute lymphoblastic 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 histopathologically detectable leukemia in SCID mice had a
significantly higher relapse rate than the 19 patients whose leukemic cells
did not (estimated 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 occurrence of overt leukemia in SCID mice was was a highly
significant predictor of patient relapse. The estimated instantaneous risk
of relapse for patients whose leukemic cells caused overt leukemia in SCID
mice was 21.5-fold greater than that for the remaining patients. Thus,
growth of human leukemic cells in SCID mice is a strong and independent
predictor of relapse in patients with newly diagnosed high-risk B-lineage
acute lymphoblastic leukemia.
Volume 85,
Issue 4,
pp. 873-878,
02/15/1995
Copyright © 1995 by The American Society of Hematology
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