Autologous bone marrow transplantation in acute myelogenous leukemia: in
vitro treatment with myeloid cell-specific monoclonal antibodies
ED Ball, LE Mills, CT Coughlin, JR Beck and GG Cornwell
Second or third chemotherapy-induced remissions in acute myelogenous
leukemia (AML) are limited by early relapse of the leukemia. We developed
monoclonal antibodies (MoAbs) that are cytotoxic to myeloid leukemia cells
to treat bone marrow from these patients ex vivo for autologous
transplantation. In this pilot study, bone marrow was harvested from ten
patients with AML in remission, treated with one or two complement-fixing
MoAbs, PM-81 and AML-2-23, which react with myeloid differentiation
antigens, incubated with rabbit complement, and cryopreserved. These MoAbs
were chosen because they have broad reactivity with AML cells but not with
pluripotent progenitor cells. At the time of transplant, 6 patients were in
second complete remission, 1 each was in third complete or partial
remission, and 2 were in early first relapse. The patients were treated
with cyclophosphamide (60 mg/kg a day for 2 days) and total body
irradiation (200 cGy twice a day for 3 days) and given infusions of
MoAb-treated bone marrow. Full bone marrow reconstitution was observed in
eight patients; two patients did not recover platelets. Seven of the ten
patients are surviving and disease-free at 21.0, 15.0, 13.0, 10.0, 6.0,
3.0, and 2.0 months posttransplant. Treating bone marrow with MoAbs to
myeloid differentiation antigens does not interfere with pluripotential
stem cell engraftment. Longer follow-up and a controlled study are
necessary to prove that the apparent efficacy of this therapeutic approach
in some patients is attributable to MoAb-mediated killing of leukemia
cells.
Volume 68,
Issue 6,
pp. 1311-1315,
12/01/1986
Copyright © 1986 by The American Society of Hematology
