HIGHLY PURIFIED CD34-POSITIVE CELLS RECONSTITUTE HEMATOPOIESIS

Purpose: The objective of this study was to characterize CD34(+) cell grafts, obtained using a novel technique, from children undergoing aut ologous bone marrow transplantation (BMT) for cancer therapy. In parti cular, we wanted to determine if the CD34(+) marrow cell grafts genera ted hematopoietic reconstitution, since a positive result would motiva te further development and use of this methodology. Patients and Metho ds: This pilot feasibility clinical trial involved 13 patients less th an or equal to 25 years of age with advanced solid rumors, including s even children with neuroblastoma. Harvested bone marrow underwent immu nomagnetic CD34(+) selection, Results: In three of 13 enrolled patient s, low purities of the CD34(+) preparations disqualified the use of th e CD34(+) marrow grafts. Ten patients received myeloablative chemother apy with etoposide, carboplatin, and cyclophosphamide, then were trans planted with CD34(+) marrow grafts. In the 10 patients transplanted wi th CD34(+)-selected cells, the CD34(+) cell purity (nucleated RBCs exc luded) in the cell graft preparation was 91% total cell recovery from tire starting light-density cells 2.2%, CD34(+) cell recovery 38%, col ony-forming unit-granulocyte-macrophage (CFU-GM) recovery 23%, and est imated tumor-cell depletion 2.6 logs (medians). The CD34(+) marrow gra fts administered to these patients contained a median of 2.3 x 10(6) n ucleated 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 myeloative chemotherapy regimen, althou gh two unusual toxicities were observed. All 10 patients transplanted with CD34(+) cell grafts engrafted. Conclusion: The CD34(+) purified g rafts were enriched in stem/progenitor cells, with five of these 10 pr eparations containing greater than or equal to 94% CD34(+) cells, Engr aftment with CD34(+)-purified cell grafts as pure as 99% confirms that autologous CD34(+) cells, alone, are sufficient to provide hematopoie tic rescue for myeloablated patients. The best purification results we re obtained on small marrow harvests from patients with neuroblastoma. The engraftment of highly purified CD34(+) cells obtained by this tec hnology and the antitumor effect of the transplant, by which two of 10 poor prognosis patients remain clinically free of tumor, have stimula ted further clinical trials. (C) 1996 by American Society of Clinical Oncology.