Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC.
We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.
Baron
F
F
Department of Medicine, Division of Hematology, University of Liège, Liège, Belgium. f.baron@ulg.ac.be
Baudoux
E
E
Frère
P
P
Tourqui
S
S
Schaaf-Lafontaine
N
N
Herens
C
C
DePrijck
B
B
Fillet
G
G
Beguin
Y
Y
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002469:Cell Separation; D005240:Feasibility Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*
D018952:Antigens, CD34