Transplantation of Highly Purified CD34+Thy-l+ Hematopoietic Stem Cells in Patients with Metastatic Breast Cancer

Robert S. Negrin, Kerry Atkinson, Tom Leemhuis, Elie Hanania, Christopher Juttner, Kathryn Tierney, Wendy W. Hu, Laura J. Johnston, Judith A. Shizuru, Keith E. Stockerl-Goldstein, Karl G. Blume, Irving L. Weisswan, Stephanie Bower, Roy Baynes, Roger Dansey, Chatchada Karanes, William Peters, Jared Klein

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

We report here the transplantation of extensively purified "mobilized" peripheral blood CD34+Thy-1+ hematopoietic stem cells from 22 patients with recurrent or metastatic breast cancer. Patients were mobilized with either high-dose granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSF. Median purity of the stem cell product at cryopreservation was 95.3% (range, 91.1%-98.3%), and viability was 98.6% (range, 96.5%-100%). After high-dose chemotherapy with carmustine, cisplatin, and cyclophosphamide, CD34+Thy-1+ cells at a median dose of 11.3 × 105 per kilogram (range, 4.7-163 × 105 per kilogram) were infused. No infusion-related toxicity was observed. Neutrophil recovery was prompt, with median absolute neutrophil count >500/μL by day 10 (range, 8-15 days) and >1000/μL by day 11 (range, 8-17 days). Median platelet recovery (>20,000/μL) was observed by day 14 (range, 9-42 days) and >50,000/μL by day 17 (range, 11-49 days). Tumor cell depletion below the limits of detection of a sensitive immunofluorescence-based assay was accomplished in all patients who had detectable tumor cells in apheresis products before processing. Although CD4+ T-cell reconstitution was slow, no unusual infections were observed. Neither early nor late graft failure was observed, and no patient required infusion of unmanipulated backup cells. At a median follow-up of approximately 1.4 years and a maximum follow-up of 2.5 years, 16 of the 22 patients remain alive, with 9 free of disease progression, and have stable blood counts. In summary, highly purified CD34+Thy-1+ cells used as the sole source of the hematopoietic graft result in rapid and sustained hematopoietic engraftment.

Original languageEnglish
Pages (from-to)262-271
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume6
Issue number3
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Breast cancer
  • Stem cells
  • Transplantation
  • Tumor purging

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    Negrin, R. S., Atkinson, K., Leemhuis, T., Hanania, E., Juttner, C., Tierney, K., Hu, W. W., Johnston, L. J., Shizuru, J. A., Stockerl-Goldstein, K. E., Blume, K. G., Weisswan, I. L., Bower, S., Baynes, R., Dansey, R., Karanes, C., Peters, W., & Klein, J. (2000). Transplantation of Highly Purified CD34+Thy-l+ Hematopoietic Stem Cells in Patients with Metastatic Breast Cancer. Biology of Blood and Marrow Transplantation, 6(3), 262-271. https://doi.org/10.1016/S1083-8791(00)70008-5