CD34+ stem cell augmentation of elutriated allogeneic bone marrow grafts: results of a phase II clinical trial of engraftment and graft-versus-host disease prophylaxis in high-risk hematologic malignancies.
Although T cell depletion of allografts used in BMT has reduced GVHD, it has been associated with inferior engraftment and an increased risk of relapse. We have found that T cell depletion by counterflow centrifugal elutriation (CCE) also results in depletion of CD34+ stem cells. In order to determine if the discarded CD34+ cells would improve engraftment, we undertook a phase II trial of allogeneic BMT in which 110 patients (median age 43) with a variety of hematologic malignancies received CD34+ stem cell augmented, elutriated marrow grafts. The T cell-depleted grafts were tightly controlled and contained a mean of 4.3 x 10(7) mononuclear cells/kg, 3.3 x 10(6) CD34+ cells/kg, 1.5 x 10(5) CFU-GM/kg and 5.5 x 10(5) CD3+ T cells/kg. Median time to engraftment of granulocytes (>500/microl) was 16 days and of platelets (>50000/microl) was 25 days, comparable to that seen with unmanipulated marrow. No mixed hematopoietic chimerism was observed that was not associated with disease relapse. The four patients (3.6%) who failed to engraft were all at high risk because of prior donor transfusions or underlying marrow disorders. The incidence of GVHD was dependent on the duration of cyclosporin A (CsA) immunosuppression. In patients who received CsA for > or = 80 days, the incidence of clinically significant acute GVHD (>stage 1) and extensive, chronic GVHD was 5% and 11%, respectively. Peritransplant (< or = 100 day post-BMT) mortality for this group of patients was 15%. Event-free survival in selected subsets of patients compared favorably to previous studies in which patients received unmanipulated marrow allografts.
O'Donnell
P V
PV
The Johns Hopkins Oncology Center, Baltimore, MD 21287, USA.
Jones
R J
RJ
Vogelsang
G B
GB
Seber
A
A
Ambinder
R F
RF
Flinn
I
I
Miller
C
C
Marcellus
D C
DC
Griffin
C
C
Abrams
R
R
Braine
H G
HG
Grever
M
M
Hess
A D
AD
Piantadosi
S
S
Noga
S J
SJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015996:Survival Rate; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D016572:Cyclosporine