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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. Blood 1999 Jul 15;94(2):434-41

Date

07/09/1999

Pubmed ID

10397710

DOI

10.1182/blood.v94.2.434

Scopus ID

2-s2.0-0033566306   76 Citations

Abstract

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 x 10(8) 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.

Author List

Drobyski WR, Hessner MJ, Klein JP, Kabler-Babbitt C, Vesole DH, Margolis DA, Keever-Taylor CA

Authors

William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
David A. Margolis MD Interim Chair, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Biomarkers, Tumor
Bone Marrow Transplantation
Cyclosporine
Female
Follow-Up Studies
Fusion Proteins, bcr-abl
Gastrointestinal Hemorrhage
Graft Enhancement, Immunologic
Graft vs Host Disease
Graft vs Tumor Effect
HLA Antigens
Histocompatibility
Humans
Immunosuppressive Agents
Incidence
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukocyte Transfusion
Life Tables
Lymphocyte Depletion
Male
Middle Aged
Neoplasm, Residual
Nuclear Family
Polymerase Chain Reaction
Salvage Therapy
Survival Analysis
T-Lymphocytes
Tissue Donors
Transplantation Conditioning
Transplantation, Homologous
Treatment Outcome