Transplantation of allogeneic CD34+ peripheral blood stem cells in patients with advanced hematologic malignancy.
Sixteen patients with advanced hematologic malignancies were transplanted with HLA-identical allogeneic peripheral blood stem cells (PBSCs) that were selected for CD34+ cells by an avidin-biotin immunoadsorption technique. The median age of patients was 48 years (range, 37 to 67). Patients received 12.0 or 13.2 Gy of total body irradiation followed by 120 mg/kg of cyclophosphamide. Normal donors received 16 mg/kg of granulocyte-colony stimulating factor on days 1 to 6 followed by PBSC harvests on days 4 to 7. PBSC harvests were processed each day on a single avidin-blotin column containing an antibody to the CD34 antigen and processed cells were infused without cryopreservation daily for 4 consecutive days. Prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine alone for 5 patients and CSA plus methotrexate for 11 patients. A median of 18.64 (6.74 to 34.97) x 10(8) CD34+ cells/kg patient body weight were collected from each donor. A median of 8.96 (2.62 to 17.34) x 10(8) CD34+ cells/kg patient body weight were recovered after avidin-biotin adsorption which represented a median CD34+ cell yield of 53% (18% to 77%) with a median purity of 62% (34% to 82%). There was a reduction in CD3+ cells from a median of 557.26 (227.73 to 677.77) x 106/kg to 0.73 x 10(4)/kg (0.40 to 3.65), in CD4+ cells from 351.72 (194.47 to 520.11) x 10(6)/kg to 0.40 (0.15 to 1.03) x 10(4)/kg and in CD8+ cells from 169.74 (53.34 to 325.83) x 10(6)/ kg to 0.32 (0.12 to 2.71) x 10(4)/kg representing a median 2.8 (2.19 to 3.14) log reduction in T cells. One patient died of infection on day 3 posttransplant and was unevaluable for recovery of neutrophils. The median day to recovery of 500 neutrophils/mL was 15 (8 to 26) in the remaining 15 patients. Six of 16 patients falled to achieve a platelet count of 20,000/mL before death on days 3 to 97 of transplant-related complications. The median day to achieving platelets of 20,000 mL in the remaining 10 patients was 11 (7 to 31). Eight of 16 patients (50%) died between 3 and 97 days posttransplant, 7 of transplant-related causes, and 1 of progressive disease. Grade 2-4 acute GVHD occurred in 12 out of 14 (86%) and grades 3-4 in 6 out of 14 (43%) evaluable patients. Six of 8 evaluable patients developed clinical chronic GVHD and 1 developed subclinical chronic GVHD. Bone marrow and/or peripheral blood chimerism studies in 12 evaluable patients showed 97% to 100% donor type in 11 patients with 1 patient in relapse showing 40% donor cells 60 to 90 days posttransplant. Four of 16 patients (25%) are alive and disease-free 312 to 576 days after transplant. There were no episodes of graft failure or rejection. This study shows that allogeneic transplantation using CD34+ selected PBSC results in prompt and sustained engraftment. CD34+ selection, as employed in this preliminary study, however, resulted in an apparently higher rate of acute and chronic GVHD. However, The sample size is quite small and precludes a more definitive conclusion regarding GVHD.
Bensinger
W I
WI
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Buckner
C D
CD
Shannon-Dorcy
K
K
Rowley
S
S
Appelbaum
F R
FR
Benyunes
M
M
Clift
R
R
Martin
P
P
Demirer
T
T
Storb
R
R
Lee
M
M
Schiller
G
G
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis*; D001773:Blood Cells; D002452:Cell Count; D002469:Cell Separation; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007163:Immunosorbent Techniques; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000401:mortality; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate