Highly purified CD34-positive cells reconstitute hematopoiesis

C. I. Civin, T. Trischmann, N. S. Kadan, Janice Davis Sproul, S. Noga, Kenneth J Cohen, B. Duffy, I. Groenewegen, J. Wiley, P. Law, A. Hardwick, F. Oldham, A. Gee

Research output: Contribution to journalArticle

Abstract

Purpose: The objective of this study was to characterize CD34+ cell grafts, obtained using a novel technique, from children undergoing outologous 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. Patients and Methods: This pilot feasibility clinical trial involved 13 patients ≤ 25 years of age with advanced solid tumors, including seven children with neuroblastoma. Harvested bone morrow underwent immunomagnetic CD34+ selection. Results: In three of 13 enrolled patients, low purifies 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 106 nucleated cells, 1.4 x 106 CD34+ cells, and 1.3 x 104 CFU-GM per kilogram patient weight. Most patients experienced only the toxicities previously observed with this myeloative chemotherapy regimen, although two unusual toxicities were observed. All 10 patients transplanted with CD34+ cell grafts engrafted. Conclusion: The CD34+ purified grafts were enriched in stem/progenitor cells, with five of these 10 preparations containing ≤ 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 fram 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.

Original languageEnglish (US)
Pages (from-to)2224-2233
Number of pages10
JournalJournal of Clinical Oncology
Volume14
Issue number8
StatePublished - 1996

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Hematopoiesis
Transplants
Bone Marrow
Granulocyte-Macrophage Progenitor Cells
Neuroblastoma
Neoplasms
Stem Cells
Clinical Trials
Drug Therapy
Carboplatin
Etoposide
Bone Marrow Transplantation
Cyclophosphamide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Civin, C. I., Trischmann, T., Kadan, N. S., Davis Sproul, J., Noga, S., Cohen, K. J., ... Gee, A. (1996). Highly purified CD34-positive cells reconstitute hematopoiesis. Journal of Clinical Oncology, 14(8), 2224-2233.

Highly purified CD34-positive cells reconstitute hematopoiesis. / Civin, C. I.; Trischmann, T.; Kadan, N. S.; Davis Sproul, Janice; Noga, S.; Cohen, Kenneth J; Duffy, B.; Groenewegen, I.; Wiley, J.; Law, P.; Hardwick, A.; Oldham, F.; Gee, A.

In: Journal of Clinical Oncology, Vol. 14, No. 8, 1996, p. 2224-2233.

Research output: Contribution to journalArticle

Civin, CI, Trischmann, T, Kadan, NS, Davis Sproul, J, Noga, S, Cohen, KJ, Duffy, B, Groenewegen, I, Wiley, J, Law, P, Hardwick, A, Oldham, F & Gee, A 1996, 'Highly purified CD34-positive cells reconstitute hematopoiesis', Journal of Clinical Oncology, vol. 14, no. 8, pp. 2224-2233.
Civin, C. I. ; Trischmann, T. ; Kadan, N. S. ; Davis Sproul, Janice ; Noga, S. ; Cohen, Kenneth J ; Duffy, B. ; Groenewegen, I. ; Wiley, J. ; Law, P. ; Hardwick, A. ; Oldham, F. ; Gee, A. / Highly purified CD34-positive cells reconstitute hematopoiesis. In: Journal of Clinical Oncology. 1996 ; Vol. 14, No. 8. pp. 2224-2233.
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title = "Highly purified CD34-positive cells reconstitute hematopoiesis",
abstract = "Purpose: The objective of this study was to characterize CD34+ cell grafts, obtained using a novel technique, from children undergoing outologous 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. Patients and Methods: This pilot feasibility clinical trial involved 13 patients ≤ 25 years of age with advanced solid tumors, including seven children with neuroblastoma. Harvested bone morrow underwent immunomagnetic CD34+ selection. Results: In three of 13 enrolled patients, low purifies 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 106 nucleated cells, 1.4 x 106 CD34+ cells, and 1.3 x 104 CFU-GM per kilogram patient weight. Most patients experienced only the toxicities previously observed with this myeloative chemotherapy regimen, although two unusual toxicities were observed. All 10 patients transplanted with CD34+ cell grafts engrafted. Conclusion: The CD34+ purified grafts were enriched in stem/progenitor cells, with five of these 10 preparations containing ≤ 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 fram 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.",
author = "Civin, {C. I.} and T. Trischmann and Kadan, {N. S.} and {Davis Sproul}, Janice and S. Noga and Cohen, {Kenneth J} and B. Duffy and I. Groenewegen and J. Wiley and P. Law and A. Hardwick and F. Oldham and A. Gee",
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T1 - Highly purified CD34-positive cells reconstitute hematopoiesis

AU - Civin, C. I.

AU - Trischmann, T.

AU - Kadan, N. S.

AU - Davis Sproul, Janice

AU - Noga, S.

AU - Cohen, Kenneth J

AU - Duffy, B.

AU - Groenewegen, I.

AU - Wiley, J.

AU - Law, P.

AU - Hardwick, A.

AU - Oldham, F.

AU - Gee, A.

PY - 1996

Y1 - 1996

N2 - Purpose: The objective of this study was to characterize CD34+ cell grafts, obtained using a novel technique, from children undergoing outologous 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. Patients and Methods: This pilot feasibility clinical trial involved 13 patients ≤ 25 years of age with advanced solid tumors, including seven children with neuroblastoma. Harvested bone morrow underwent immunomagnetic CD34+ selection. Results: In three of 13 enrolled patients, low purifies 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 106 nucleated cells, 1.4 x 106 CD34+ cells, and 1.3 x 104 CFU-GM per kilogram patient weight. Most patients experienced only the toxicities previously observed with this myeloative chemotherapy regimen, although two unusual toxicities were observed. All 10 patients transplanted with CD34+ cell grafts engrafted. Conclusion: The CD34+ purified grafts were enriched in stem/progenitor cells, with five of these 10 preparations containing ≤ 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 fram 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.

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