[en] To decrease the incidence of graft-versus-host disease (GVHD) observed after nonmyeloablative stem cell transplantation (NMSCT), we studied the feasibility of CD8-depleted or CD34-selected NMSCT followed by CD8-depleted preemptive donor lymphocyte infusion (DLI) given in incremental doses on days 40 and 80. Fourteen patients with high-risk malignancies and an HLA-identical sibling (n = 8) or alternative donor (n = 6) but ineligible for a conventional transplant were included. Nonmyeloablative conditioning regimen consisted in 2 Gy total body irradiation (TBI) alone, 2 Gy TBI and fludarabine (previously untreated patients) or cyclophosphamide and fludarabine (patients who had previously received > or =12 Gy TBI). Patients 1-4 (controls) received unmanipulated peripheral blood stem cells (PBSC) and DLI and patients 5-14 CD8-depleted or CD34-selected PBSC followed by CD8-depleted DLI. Post-transplant immunosuppression was carried out with cyclosporine A (CsA) and mycophenolate mofetil (MMF). Initial engraftment was seen in all patients, but 1 patient (7%) later rejected her graft. The actuarial 180-day incidence of grades II-IV acute GVHD was 75% for patients 1-4 versus 0% for patients 5-14 (p = 0.0019). Five of 14 patients were in complete remission (CR) 180 days after the transplant and 6/14 had partial responses. The 1-year survival rate was 69%, and nonrelapse and relapse mortality rates were 16 and 18%, respectively. We conclude that CD8-depleted or CD34-selected NMSCT followed by CD8-depleted DLI is feasible and considerably decreases the incidence of acute GVHD while preserving engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.
Disciplines :
Hematology
Author, co-author :
Baron, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Baudoux, Etienne ; Centre Hospitalier Universitaire de Liège - CHU > Thérapie cellulaire
Frere, Pascale ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Tourqui, Soraya
Schaaf-Lafontaine, Nicole ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Greimers, Roland ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Herens, Christian ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Fillet, Georges ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Beguin, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Language :
English
Title :
Nonmyeloablative stem cell transplantation with CD8-depleted or CD34-selected peripheral blood stem cells.
Publication date :
2002
Journal title :
Journal of Hematotherapy and Stem Cell Research
ISSN :
1525-8165
Publisher :
Mary Ann Liebert, Inc., Larchmont, United States - New York
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