GROWTH-PATTERN AND CLINICAL CORRELATION OF SUBCUTANEOUSLY INOCULATED HUMAN PRIMARY ACUTE LEUKEMIAS IN SEVERE COMBINED IMMUNODEFICIENCY MICE

We examined the ability of patient-derived human leukemic blasts to ge nerate leukemic growth and dissemination in severe combined immunodefi ciency (SCID) mice by subcutaneous inoculation without conditioning tr eatment or administration of growth-promoting cytokines. Additionally, we correlated the growth pattern with the clinical outcome of patient s from whom the leukemic cells were derived. The leukemias displayed t hree distinct growth patterns, ie, either aggressive, indolent, or no tumor growth. Leukemic cells from 6 of 13 patients with acute myeloid leukemia (AML), 4 of 7 T-cell acute lymphoblastic leukemia (T-ALL), an d 11 of 16 patients with B-lineage ALL grew as subcutaneous tumors, wi th a significant number subsequently disseminating into distant organs in SCID mice. Patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SCID mice had a relatively poor cl inical outcome, whereas patients with AML and T- or B-lineage ALL whos e leukemic blasts grew indolently or whose cells failed to induce grow th had a more favorable clinical course. Our study has shown that the subcutaneous inoculation of patient-derived human leukemic cells in SC ID mice can engraft and grow as subcutaneous tumors with subsequent di ssemination to distant organs in a manner analogous to their pattern o f growth in humans. Additionally, these data suggest a clinical correl ation to the growth and dissemination of some leukemic subtypes that m ay represent not only an additional prognosticator for patient outcome , but also a vehicle for the study of the biologic behavior of human l eukemias and the development of novel therapeutic strategies. (C) 1996 by The American Society of Hematology.