Article (Scientific journals)
Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation.
Baron, Frédéric; Siquet, Jean; Schaaf-Lafontaine, Nicole et al.
2002In Haematologica, 87 (1), p. 78-88
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Keywords :
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
Abstract :
[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.
Disciplines :
Hematology
Author, co-author :
Baron, Frédéric  ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Siquet, Jean
Schaaf-Lafontaine, Nicole ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Baudoux, Etienne  ;  Centre Hospitalier Universitaire de Liège - CHU > Thérapie cellulaire
Hermanne, Jean-Philippe
Fillet, Georges ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Beguin, Yves  ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Language :
English
Title :
Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation.
Publication date :
2002
Journal title :
Haematologica
ISSN :
0390-6078
eISSN :
1592-8721
Publisher :
Ferrata Storti Foundation, Pavia, Italy
Volume :
87
Issue :
1
Pages :
78-88
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 16 February 2009

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