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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 434-441
T-Cell Depletion Plus Salvage Immunotherapy With Donor Leukocyte
Infusions as a Strategy to Treat Chronic-Phase Chronic Myelogenous
Leukemia Patients Undergoing HLA-Identical Sibling Marrow
Transplantation
William R. Drobyski,
Martin J. Hessner,
John P. Klein,
Claudia Kabler-Babbitt,
David H. Vesole, and
Carolyn A. Keever-Taylor
From the Bone Marrow Transplant Program, Departments of Medicine and
Biostatistics, Medical College of Wisconsin, Milwaukee, WI; and the
Blood Center of Southeastern Wisconsin, Milwaukee, WI.
T-cell depletion (TCD) of the donor marrow graft has been shown to
reduce the severity of graft-versus-host disease (GVHD) in patients
with chronic-phase (CP) chronic myelogenous leukemia (CML) undergoing
HLA-identical sibling allogeneic marrow transplantation. However, there
has been a corresponding reduction in the graft-versus-leukemia effect
so that any decrease in GVHD-related mortality has been offset by an
increased rate of disease relapse. Therapy of recurrent disease with
donor leukocyte infusions (DLI) has been proven to be effective salvage
therapy for the majority of patients who relapse after allogeneic BMT
with CP CML. However, the overall impact of salvage DLI therapy on the
survival of CP CML patients initially transplanted with TCD marrow
grafts is not defined. To address this question, we have evaluated a
clinical strategy of TCD followed by targeted adoptive immunotherapy
with DLI in 25 CP CML patients undergoing allogeneic BMT from
HLA-identical siblings. All patients received a standardized
preparative regimen along with ex vivo TCD and posttransplant
cyclosporine as GVHD prophylaxis. Durable engraftment was observed in
all 25 patients. The incidence of grade II to IV acute GVHD was 8%.
The cumulative incidence of transplant-related mortality (TRM) was 4%,
and the 1-year probability of overall survival was 96%. The 3-year
cumulative relapse incidence was 49%. All relapsed patients received
DLI to reinduce remission. The total T-cell dose administered to these patients varied from 0.1 to 5.0 × 108 T cells/kg.
Complete responses were observed in 12 of 14 patients, with 1 additional patient still too early to evaluate. Three patients died of
GVHD after DLI, and 1 relapsed into blast crisis after a transient
cytogenetic remission. Of the remaining 10 patients, 8 are in molecular
remission, 1 is alive in relapse, and 1 is receiving DLI treatment. The
median follow-up after infusion of surviving DLI patients in remission
is 5.3 years. The probability of overall 5-year survival for the entire
population is 80%, with a median follow-up of 6.4 years. We conclude
that the clinical strategy of TCD followed by targeted adoptive
immunotherapy with DLI for those patients with evidence of recurrent
disease is a viable transplant strategy for CP CML, resulting in 80%
survival and a low risk of acute GVHD and transplant-related mortality.
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