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

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.