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Salvage immunotherapy using donor leukocyte infusions as treatment for
relapsed chronic myelogenous leukemia after allogeneic bone marrow
transplantation: efficacy and toxicity of a defined T-cell dose
WR Drobyski, CA Keever, MS Roth, S Koethe, G Hanson, P McFadden, JL Gottschall, RC Ash, P van Tuinen and MM Horowitz
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Eight patients who had hematologic relapse of chronic myelogenous leukemia
(CML) after undergoing allogeneic bone marrow transplantation (BMT) were
treated with leukocyte infusions from the original bone marrow donors. All
patients had previously received marrow grafts from HLA-identical siblings.
Six patients were in the accelerated phase of their disease and two were in
blast crisis. Each patient received a predetermined T-cell dose within a
narrow range of 2.5 to 5.0 x 10(8) T cells/kg. Three patients also received
short courses of therapy with alpha interferon to control elevated white
blood cell counts within the first several weeks after leukocyte
transfusions. Seven of eight evaluable patients developed graft-versus-host
disease (GVHD) at a median of 32 days after the initial infusion. One
patient had fatal GVHD. A second patient had grade 3 acute GVHD, which has
responded to immunosuppressive therapy. The remaining patients all had mild
grade I GVHD. Six patients continue to require modest doses of prednisone
more than 6 months after infusion. Four patients developed marrow aplasia,
which in three patients required marrow boosts from the original donors.
Two of these three patients have normal hematopoietic function, whereas the
third patient remains growth factor and transfusion dependent. Both
patients treated in blast crisis have died, one from GVHD and one from
disease progression. All six patients in the accelerated phase are alive
and in cytogenetic remission at a median of 42 weeks after infusion. Five
of these six patients are in molecular remission. This study demonstrates
that leukocyte infusions that administered a defined T-cell dose can exert
a profound graft-versus- leukemia effect and are an effective form of
salvage immunotherapy in allogeneic marrow transplant recipients. This
therapeutic approach appears to be a viable alternative to existing
chemotherapeutic and immunomodulatory strategies for the treatment of
relapsed CML.
Volume 82,
Issue 8,
pp. 2310-2318,
10/15/1993
Copyright © 1993 by The American Society of Hematology
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