Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: Influence of CD34-positive peripheral-blood progenitors and growth factors on engraftment

Purpose: To evaluate the capacity of enriched CD34-positive (CD34⁺) progenitor cells to reconstitute hematopoiesis in poor-prognosis breast cancer patients following administration of a high-dose alkylating agent chemotherapy regimen. Patients and Methods: Forty-four breast cancer patients received high-dose chemotherapy followed by autologous bone marrow support (ABMS) with CD34⁺ hematopoietic progenitor cells in five sequentially treated cohorts. Following infusion of CD34⁺ marrow, cohort no. 1 received no growth factor, cohort no. 2 received granulocyte colony-stimulating factor (G-CSF), and cohort no. 3 received granulocyte-macrophage colony-stimulating factor (GM-CSF). Cohort no. 4 received the CD34⁺ fractions of both marrow and peripheral-blood progenitor cells (PBPCs) plus G-CSF. Cohort no. 5 received only the CD34⁺ PBPCs plus G-CSF. Immunohistochemical staining for breast cancer was performed on all hematopoietic cell products before and after the positive selection procedure, to assess quantitatively the level of tumor-cell contamination. Results: Cohorts no. 1, 2, 3, 4, and 5 achieved a granulocyte count ≥ 500 x 10⁹/L in a median of 23, 10, 16, 11, and 11 days, with a platelet count greater than 20,000 x 10⁹/L documented in a median of 22, 23, 32, 12, and 10 days, respectively. The time to granulocyte reconstitution was significantly shorter for patients who received CD34⁺ PBPCs alone (cohort no. 5), or in combination with CD34⁺ marrow (cohort no. 4), when compared with those who received only the CD34⁺ marrow fraction (P < .01). From 1 to greater than 4 logs of breast cancer cell depletion were documented after CD34-selection, for patients in whom tumor was initially detected. Conclusion: CD34⁺ marrow and/or PBPCs provide reliable and timely hematopoietic reconstitution in breast cancer patients receiving high-dose chemotherapy. Contamination of both marrow and PBPCs with breast cancer cells was reduced using this positive selection technique.