Nonmyeloablative stem cell transplantation with CD8-depleted or CD34-selected peripheral blood stem cells

被引:19
作者
Baron, F
Baudoux, E
Frère, P
Tourqui, S
Schaaf-Lafontaine, N
Greimers, R
Herens, C
Fillet, G
Beguin, Y
机构
[1] Univ Liege, Dept Med, Div Hematol, B-4000 Liege, Belgium
[2] Univ Liege, Dept Transfus Med, B-4000 Liege, Belgium
[3] Univ Liege, Dept Biol Clin, Div Lab Hematol, B-4000 Liege, Belgium
[4] Univ Liege, Dept Pathol, B-4000 Liege, Belgium
[5] Univ Liege, Dept Genet, B-4000 Liege, Belgium
来源
JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH | 2002年 / 11卷 / 02期
关键词
D O I
10.1089/152581602753658484
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 greater than or equal to12 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.
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收藏
页码:301 / 314
页数:14
相关论文
共 53 条
[1]   Adoptive immunotherapy: insights from donor lymphocyte infusions [J].
Alyea, E .
TRANSFUSION, 2000, 40 (04) :393-395
[2]   Adoptive immunotherapy with donor lymphocyte infusions after allogeneic HPC transplantation [J].
Baron, F ;
Beguin, Y .
TRANSFUSION, 2000, 40 (04) :468-476
[3]  
Baron F, 2002, HAEMATOLOGICA, V87, P78
[4]   Nonmyeloablative allogeneic hematopoietic stem cell transplantation [J].
Baron, F ;
Beguin, Y .
JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH, 2002, 11 (02) :243-263
[5]  
Baron F, 2001, HAEMATOLOGICA, V86, P993
[6]   T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect [J].
Barrett, AJ ;
Mavroudis, D ;
Tisdale, J ;
Molldrem, J ;
Clave, E ;
Dunbar, C ;
Cottler-Fox, M ;
Phang, S ;
Carter, C ;
Okunnieff, P ;
Young, NS ;
Read, EJ .
BONE MARROW TRANSPLANTATION, 1998, 21 (06) :543-551
[7]   Non-myeloablative stem cell transplants [J].
Barrett, J ;
Childs, R .
BRITISH JOURNAL OF HAEMATOLOGY, 2000, 111 (01) :6-17
[8]   The benefits of an alloresponse: Graft-versus-tumor [J].
Barrett, J ;
Childs, R .
JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH, 2000, 9 (03) :347-354
[9]   REGIMEN-RELATED TOXICITY IN PATIENTS UNDERGOING BONE-MARROW TRANSPLANTATION [J].
BEARMAN, SI ;
APPELBAUM, FR ;
BUCKNER, CD ;
PETERSEN, FB ;
FISHER, LD ;
CLIFT, RA ;
THOMAS, ED .
JOURNAL OF CLINICAL ONCOLOGY, 1988, 6 (10) :1562-1568
[10]   Dose-reduced conditioning for allogeneic blood stem cell transplantation:: durable engraftment without antithymocyte globulin [J].
Bornhäuser, M ;
Thiede, C ;
Schuler, U ;
Platzbecker, U ;
Freiberg-Richter, J ;
Helwig, A ;
Plettig, R ;
Röllig, C ;
Naumann, R ;
Kroschinsky, F ;
Neubauer, A ;
Ehninger, G .
BONE MARROW TRANSPLANTATION, 2000, 26 (02) :119-125