Use of recombinant human interleukin-2 in conjunction with syngeneic bone
marrow transplantation in mice as a model for control of minimal residual
disease in malignant hematologic disorders
A Ackerstein, E Kedar and S Slavin
Department of Bone Marrow Transplantation Hadassah University Hospital,
Jerusalem, Israel.
Unlike allogeneic bone marrow transplantation (BMT), autologous BMT is not
accompanied by immune-mediated graft-versus-leukemia (GVL) effects; hence,
the relapse rate observed after autologous BMT in malignant hematologic
disorders is higher than that observed after allogeneic BMT. Autologous BMT
represents a much safer medical procedure available for many patients in
need in situations where allogeneic BMT is not feasible or risky. The
present experiments were designed to investigate whether it might be
possible to combine the therapeutic benefits of autologous BMT with
additional immunotherapy after BMT. The tumor model used for investigating
GVL effects was the murine B-cell leukemia (BCL1), a spontaneous,
nonimmunogenic, highly lethal leukemia of BALB/c origin. BALB/c mice
inoculated with 10(3) BCL1 leukemia cells were treated on day-1 with
cyclophosphamide 100 mg/kg and transplanted with normal syngeneic BM cells
on day 0. High-dose recombinant interleukin-2 (rIL-2) (100,000 Cetus units
x 3/day intraperitoneally x 5 consecutive days) was initiated on day +1,
+7, or +21 after BMT. Kinetics of lymphocyte reconstitution after syngeneic
BMT indicated a steep increase in the absolute number of peripheral blood
lymphocytes on days 17 through 24. All experimental groups were observed
for relapse. Mice receiving no rIL-2 therapy relapsed and died within 50
days after BMT, whereas mice receiving rIL-2 showed long-term disease-free
survival. Optimal time for administration of rIL-2 was noted at 3 weeks
post-BMT, with 90% of the mice surviving with no evidence of disease for
more than 1 year. Similarly, when 10(4) BCL1 cells were given 1 day after
syngeneic BMT to simulate minimal residual disease after syngeneic BMT,
rIL-2 therapy administered at 14 days post-BMT seemed effective in
prolonging disease-free survival in contrast to the same regimen given at 1
day after BMT. Our data suggest that immunotherapy with rIL-2 should be
further investigated as a new immunotherapeutic tool for decreasing the
relapse rate after BMT for hematologic malignancies.
Volume 78,
Issue 5,
pp. 1212-1215,
09/01/1991
Copyright © 1991 by The American Society of Hematology
