Allogeneic transplantation of selected CD34+ cells from peripheral blood: experience of 62 cases using immunoadsorption or immunomagnetic technique. Spanish Group of Allo-PBT.
The objective of this study was to analyze CD34+ cell recovery and T cell depletion (TCD) achieved in CD34+ cell grafts using either immunoadsorption or immunomagnetic methods applied to leukapheresis products from healthy donors. We also wanted to determine the kinetics of engraftment and incidence and severity of graft-versus-host disease (GVHD) after allogeneic transplantation of selected CD34+ cells. HLA-identical sibling donors received G-CSF. After leukapheresis, peripheral blood progenitor cells were selected using immunoadsorption (Ceprate SC) (n = 38) or immunomagnetic (Isolex 300) (n = 24) methods. Sixty-two patients, with a median age of 42 years (range 17-60) diagnosed with hematological malignancies were conditioned with either cyclophosphamide and total body irradiation (n = 43) or busulphan and cyclophosphamide (n = 19). GVHD prophylaxis consisted of cyclosporin A (CsA) and prednisone (n = 48), CsA alone (n = 11) and CsA and methotrexate (n = 3). The median yield and purity of CD34+ cells after the procedure was 65 and 66% with immunoadsorption, and 48 and 86% with immunomagnetic method, respectively. The median number (range) of CD34+ cells infused into the patients was 3.5 x 10(6)/kg (1-9.6). The median number (range) of CD3+ cells administered was 0.4 x 10(6)/kg (0.01-2) using immunoadsorption and 0.14 x 10(6)/kg (0.03-2.5) using immunomagnetic methods. Neutrophil recovery >500 and >1000/microl was achieved at a median (range) of 13 days (8-22) and 14 days (9-31), respectively. Platelets recovered to >20000 and >50000/microl at a median (range) of 13 days (0-128) and 18 days (0-180), respectively. Two patients developed graft failure. Acute GVHD in patients at risk was clinical grade 0 (n = 43), I (n = 8), II (n = 4) and III (n = 1). No patient developed acute GVHD grade IV. Chronic GVHD was limited in two cases and extensive in four cases. The actuarial probability of acute GVHD II-IV was 10% (95% CI, 1-19%), and of extensive chronic GVHD was 12% (95% CI, 11-13%). The cumulative incidence of transplant-related mortality was 12.6%, and this figure was 9% at 6 months. In conclusion, with the immunomagnetic procedure, a lower recovery and higher purity of CD34+ cells, and stronger TCD is obtained as compared to immunoadsorption (P = 0.008, P < 0.0001 and P = 0.0002, respectively). Our results also indicate that allogeneic transplantation of selected CD34+ cells is associated with a very rapid engraftment and with a low incidence of severe GVHD.
Urbano-Ispizua
A
A
Solano
C
C
Brunet
S
S
de la Rubia
J
J
Odriozola
J
J
Zuazu
J
J
Figuera
A
A
Caballero
D
D
Martínez
C
C
García
J
J
Sanz
G
G
Torrabadella
M
M
Alegre
A
A
Pérez-Oteiza
J
J
Jurado
M
M
Oyonarte
S
S
Sierra
J
J
García-Conde
J
J
Rozman
C
C
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000097:blood*; D002908:Chronic Disease; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D018189:Immunomagnetic Separation; D007163:Immunosorbent Techniques; D007700:Kinetics; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D018952:Antigens, CD34