Highly purified CD34-positive cells reconstitute hematopoiesis.
OBJECTIVE
The objective of this study was to characterize CD34+ cell grafts, obtained using a novel technique, from children undergoing autologous bone marrow transplantation (BMT) for cancer therapy. In particular, we wanted to determine if the CD34+ marrow cell grafts generated hematopoietic reconstitution, since a positive result would motivate further development and use of this methodology.


METHODS
This pilot feasibility clinical trial involved 13 patients < or = 25 years of age with advanced solid tumors, including seven children with neuroblastoma. Harvested bone marrow underwent immunomagnetic CD34+ selection.


RESULTS
In three of 13 enrolled patients, low purities of the CD34+ preparations disqualified the use of the CD34+ marrow grafts. Ten patients received myeloablative chemotherapy with etoposide, carboplatin, and cyclophosphamide, then were transplanted with CD34+ marrow grafts. In the 10 patients transplanted with CD34(+)-selected cells, the CD34+ cell purity (nucleated RBCs excluded) in the cell graft preparation was 91% total cell recovery from the starting light-density cells 2.2%, CD34+ cell recovery 38%, colony-forming unit-granulocyte-macrophage (CFU-GM) recovery 23%, and estimated tumor-cell depletion 2.6 logs (medians). The CD34+ marrow grafts administered to these patients contained a median of 2.3 x 10(6) nucleated cells, 1.4 x 10(6) CD34+ cells, and 1.3 x 10(4) CFU-GM per kilogram patient weight. Most patients experienced only the toxicities previously observed with this myeloblative chemotherapy regimen, although two unusual toxicities were observed. All 10 patients transplanted with CD34+ cell grafts engrafted.


CONCLUSIONS
The CD34+ purified grafts were enriched in stem/progenitor cells, with five of these 10 preparations containing > or = 94% CD34+ cells. Engraftment with CD34(+)-purified cell grafts as pure as 99% confirms that autologous CD34+ cells, alone, are sufficient to provide hematopoietic rescue for myeloablated patients. The best purification results were obtained on small marrow harvests from patients with neuroblastoma. The engraftment of highly purified CD34+ cells obtained by this technology and the antitumor effect of the transplant, by which two of 10 poor prognosis patients remain clinically free of tumor, have stimulated further clinical trials.
Civin
C I
CI
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. CIVINCI@AOL.com
Trischmann
T
T
Kadan
N S
NS
Davis
J
J
Noga
S
S
Cohen
K
K
Duffy
B
B
Groenewegen
I
I
Wiley
J
J
Law
P
P
Hardwick
A
A
Oldham
F
F
Gee
A
A
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D005240:Feasibility Studies; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000401:mortality / Q000628:therapy; D010865:Pilot Projects; D015996:Survival Rate; D014182:Transplantation, Autologous
D018952:Antigens, CD34