LONG-TERM MALIGNANT HEMATOPOIESIS IN HUMAN ACUTE-LEUKEMIA BONE-MARROWBIOPSIES IMPLANTED IN SEVERE COMBINED IMMUNODEFICIENCY MICE

Bone marrow (BM) trephine biopsies from 15 pediatric patients with acu te lymphoid (ALL) or myeloid (AML) leukemia were engrafted subcutaneou sly into severe combined immunodeficiency (SCID) mice conditioned by 2 00 cGy total-body irradiation. Implants were harvested 5 to 19 weeks l ater for histologic, cytologic, and/or flow cytometric analysis of the residing marrow. Eighteen of 19 grafts contained viable human leukemi c cells to various extents as assessed by one or more of these methods . Thirteen of 14 implants analyzed by flow cytometry included high num bers of tumor cells, accounting for 85% to 100% of the total nucleated cells in seven of them. Histologically, engrafted marrow samples exhi bited areas of blastic infiltration, and tumor-specific gene rearrange ments were retrieved in long-term engrafted biopsies. Importantly, eng rafted mice remained perfectly healthy even 5 months posttransplantati on, and no human tumor cell dissemination was detected in the hematoly mphoid and nonhematopoietic tissues at the time of autopsy. These resu lts demonstrate that human malignant hematopoiesis can be sustained lo ng-term in its original, intact marrow stromal environment transplante d in appropriately conditioned immunodeficient mice. (C) 1997 hy The A merican Society of Hematology.