Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation.
We have selectively depleted host-reactive donor T cells from peripheral blood stem cell (PBSC) transplant allografts ex vivo using an anti-CD25 immunotoxin. We report a clinical trial to decrease graft-versus-host disease (GVHD) in elderly patients receiving selectively depleted PBSC transplants from HLA-identical sibling donors. Sixteen patients (median age, 65 years [range, 51-73 years]), with advanced hematologic malignancies underwent transplantation following reduced-intensity conditioning with fludarabine and either cyclophosphamide (n = 5), melphalan (n = 5), or busulfan (n = 6). Cyclosporine was used as sole GVHD prophylaxis. The allograft contained a median of 4.5 x 10(6) CD34 cells/kg (range, 3.4-7.3 x 10(6) CD34 cells/kg) and 1.0 x 10(8)/kg (range, 0.2-1.5 x 10(8)/kg) selectively depleted T cells. Fifteen patients achieved sustained engraftment. The helper T-lymphocyte precursor (HTLp) frequency assay demonstrated successful (mean, 5-fold) depletion of host-reactive donor T cells, with conservation of third-party response in 9 of 11 cases tested. Actuarial rates of acute GVHD were 46% +/- 13% for grades II to IV and 12% +/- 8% for grades III to IV. These results suggest that allodepletion of donor cells ex vivo is clinically feasible in older patients and may reduce the rate of severe acute GVHD. Further studies with selectively depleted transplants to evaluate graft-versus-leukemia (GVL) and survival are warranted.
Solomon
Scott R
SR
Stem Cell Allogeneic Transplantation Section, Hematology Branch, NHLBI, NIH Bldg 10, Hatfield CRC, Rm 3-5320, 10 Center Dr, MSC 1202, Bethesda, MD 20892-1202, USA.
Mielke
Stephan
S
Savani
Bipin N
BN
Montero
Aldemar
A
Wisch
Laura
L
Childs
Richard
R
Hensel
Nancy
N
Schindler
John
J
Ghetie
Victor
V
Leitman
Susan F
SF
Mai
Thao
T
Carter
Charles S
CS
Kurlander
Roger
R
Read
Elizabeth J
EJ
Vitetta
Ellen S
ES
Barrett
A John
AJ
D000368:Aged; D002469:Cell Separation / Q000379:methods*; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D012008:Recurrence; D035781:Siblings; D018183:Transplantation Chimera; D014184:Transplantation, Homologous