CD34 augmentation improves allogeneic T cell-depleted bone marrow engraftment.
T cell depletion (TCD) performed by elutriation has decreased the incidence of acute and chronic graft-versus-host disease (GvHD) following bone marrow transplantation (BMT). However, as with all forms of TCD, patients may experience graft failure (10%), delayed engraftment, and mixed chimerism. Because 66%-75% of the CD34+ cells coseparate with the small lymphocytes, which are removed by elutriation, we designed a phase I trial in HLA-identical siblings to determine if the readdition of these previously lost small CD34+ cells would improve elutriation's engraftment kinetics. CD34+ cells were isolated from the small cell fraction of 10 consecutive donor grafts and infused into the recipients along with the TCD graft. The positively selected product had a mean T cell content of 1.2 x 10(5)/kg and was 80% CD34+, doubling the CD34+ content of the graft. All patients engrafted promptly with a median time to 500 neutrophils/mm3, untransfused 50,000 platelets/mm3, and discharge from the hospital of 19 (range 10-25), 24 (14-52), and 24 (18-29) days, respectively. Acute GvHD occurred in 2 patients, and no patient had chronic GvHD. Augmenting stem cell dose may be an efficient and safe alternative for overcoming TCD-associated delayed engraftment and graft failure, rather than increasing immunosuppression.
Noga
S J
SJ
Johns Hopkins Oncology Center, Baltimore, MD 21287, USA.
Seber
A
A
Davis
J M
JM
Berenson
R J
RJ
Vogelsang
G B
GB
Braine
H G
HG
Hess
A D
AD
Marcellus
D
D
Miller
C A
CA
Sharkis
S J
SJ
Goodman
S N
SN
Santos
G W
GW
Jones
R J
RJ
D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D002469:Cell Separation; D005260:Female; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D010865:Pilot Projects; D017741:Survivors; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D018952:Antigens, CD34