Reference : Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected alloge...
Scientific journals : Article
Human health sciences : Hematology
http://hdl.handle.net/2268/6309
Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation.
English
Baron, Frédéric mailto [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie clinique >]
Siquet, Jean [> > > >]
Schaaf-Lafontaine, Nicole mailto [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie biologique et immuno hématologie >]
Baudoux, Etienne mailto [Centre Hospitalier Universitaire de Liège - CHU > > Thérapie cellulaire >]
Hermanne, Jean-Philippe [> > > >]
Fillet, Georges mailto [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie clinique >]
Beguin, Yves mailto [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie clinique >]
2002
Haematologica
Ferrata Storti Foundation
87
1
78-88
Yes (verified by ORBi)
International
0390-6078
1592-8721
Pavia
Italy
[en] Adolescent ; Adult ; Antigens, CD8 ; Cytomegalovirus Infections/etiology ; Feasibility Studies ; Female ; Graft Survival ; Graft vs Host Disease/epidemiology/prevention & control ; Graft vs Leukemia Effect ; Hematologic Neoplasms/mortality/therapy ; Hematopoietic Stem Cell Transplantation/adverse effects/statistics & numerical data ; Histocompatibility ; Humans ; Incidence ; Leukapheresis ; Lymphocyte Depletion ; Lymphocyte Transfusion/statistics & numerical data ; Male ; Middle Aged ; Survival Analysis ; Transplantation, Homologous/statistics & numerical data ; Treatment Outcome ; Virus Activation
[en] BACKGROUND AND OBJECTIVES: To maximize graft-versus-leukemia (GVL) effects while minimizing the risk of graft-versus-host disease (GVHD), we undertook a study of allogeneic CD34-selected peripheral blood stem cell (PBSC) transplantation followed by CD8-depleted donor lymphocyte infusion (DLI). DESIGN AND METHODS: Twenty-four patients with advanced hematologic malignancies were included. PBSC were collected in matched (N=16) or one-mismatch (N=8) related donors and CD34-selected. On day 60, donors donated lymphocytes that were CD8-depleted and separated into 3 aliquots containing 2 x 10(6), 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 1-13) or into 2 aliquots containing 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 14-24). The 1st aliquot was infused on day 60 and the other 1 (2) cryopreserved and infused on days 100 (and 140). RESULTS: An average of 100%, 100% and 84% of the scheduled dose could be administered in DLI 1, 2 and 3, respectively. Although the study group was at very high risk of GVHD, the actuarial incidence of grade II-IV acute GVHD was 28% (13% for HLA-identical siblings) with only 1 patient developing grade III-IV GVHD (after DLI). The actuarial 2-year probability of extensive chronic GVHD was similarly low (13% for all patients and 0% for HLA-identical siblings). Individual cases as well as a 30% relapse rate (0% for standard-risk patients versus 55% for high-risk patients) indicated preservation of the GVL effect. INTERPRETATION AND CONCLUSIONS: We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to prove that it preserves the GVL effect fully.
http://hdl.handle.net/2268/6309

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