Tumor cell depletion of peripheral blood progenitor cells using positive and positive/negative selection in metastatic breast cancer

R. A. Preti*, H. M. Lazarus, Jane Norma Winter, E. A. Stadtmauer, S. Nadasi, J. McMannis, S. Karandish, A. Jennis, S. L. Goldberg, A. L. Pecora

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Background: The clinical relevance of tumor cell purging of hematopoietic progenitor cell grafts has yet to be conclusively determined. Therefore, in addition to the demonstration that a method for graft purification is capable of removing an adequate number of tumor cells, it is critical that the procedure has as benign an impact upon the hematopoietic repopulating potential of the graft as possible. We evaluated tumor cell depletion, recovery of CD34+ cells and post transplant engraftment kinetics as accepted measures of the effectiveness of an immunomagnetic bead (positive and positive/negative) purging methodology. Methods: The patients received either positive selection (CD34 selection alone) or a combination of positive and negative (CD34 selection followed by breast cancer cell depletion) using the Isolex 300 (automated and semi-automated) devices. Immunocytochemistry was used to determine the degree of breast cancer cell contamination before and after the selection procedures to determine the efficacy of the procedure. CD34 enumeration was employed to evaluate the recovery and purity of the CD34-selected cellular products and engraftment indices (days to absolute neutrophil count (ANC) recovery and platelet count (Plt) recovery and transfusion requirements) were evaluated to determine the safety of the procedure. Results: A total of 130 aphereses was performed on 101 patients. Ten pairs of collections were pooled before selection to increase the likelihood of achieving CD34 dose goals after selection. In all, 100 positive selections and 20 positive/negative selections were performed. Of the 10 (10.4%) ICC-positive preselection samples, 2 products showed persistent contamination after processing. The majority of patients (85.4%) required one selection procedure to achieve an adequate CD34+ selected cell dose. Median CD34+ cell recovery was > 50% for positive selection procedures and >60% for the positive/negative procedures. The dose of CD34+ cells infused ranged from 0.76 × 106 CD34+ cells/kg to 27.7 × 106 CD34+ cells/kg. There were no significant delays in neutrophil or platelet recovery or infections between any of the treatment groups. Discussion: CD34 selection alone or in combination with negative selection can result in a significant reduction of contaminating tumor cells in the peripheral blood progenitor cell autograft. Although there was one engraftment failure with the CD34-positive selected cells, transplantation of the selected products after high-dose chemotherapy for metastatic breast cancer did not result in a clinically significant delay in the hematopoietic reconstitutive capacity of the autografts.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalCytotherapy
Volume3
Issue number2
DOIs
StatePublished - Jan 1 2001

Keywords

  • CD34 selection
  • Immunomagnetic beads
  • Isolex
  • Metastatic breast cancer transplantation
  • Negative selection
  • Positive selection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

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