Source of stem cells impacts on hematopoietic recovery after high-dose chemotherapy

The restoration of hematopoiesis after high-dose chemotherapy may be accelerated by the use of stem cells from the bone marrow (BM) or peripheral blood. Numerous reports utilizing mobilized peripheral blood progenitor cells (PBPC) for stem cell rescue have shown that PBPC are sufficient to restore hematopoiesis, but there are little data comparing the recovery among patients treated with various stem cell sources. We reviewed the clinical outcomes of 69 women at our institution, who were treated for locally advanced or metastatic breast cancer with high-dose cyclophosphamide (CY) and thiotepa and autologous stem cell and growth factor support. Of the 43 patients with normal BM, 19 received BM alone and 24 received BM plus G-CSF mobilized PBPC. Of the 26 patients with evidence of metastatic disease in the BM, or evidence of fibrosis and hypocellularity, 15 received CY-mobilized PBPC and 11 received CY/G-CSF-mobilized PBPC. Of the marrow-negative patients, those receiving BM alone had significantly longer (P < 0.001) granulocyte recovery (absolute neutrophil count >500 x 10⁶/l) and platelet recovery (platelets >50 x 10⁹/l) compared with BM+G-CSF-mobilized PBPC. They also had significantly longer (P < 0.001) durations of antibiotic and amphotericin usage, increased transfusion requirements and longer hospitalizations. Of the marrow-positive patients, there was a slightly shortened granulocyte recovery, shortened hospital stays and lessened amphotericin usage in the patients who received CY/G-CSF-mobilized PBPC compared with the CY-mobilized patients. Although the number of harvested mononuclear cells differed significantly between the groups, this did not correlate with the time to hematopoietic recovery. There was no quantitative assessment of CD34⁺ cells and CFU-GM (colony-forming units granulocyte-macrophage) for the BM alone group, but there was no significant difference seen in the number of harvested CD34-positive cells among the remaining three groups. There was a weak statistical trend towards increased CFU-GM in the patients mobilized with CY/G-CSF compared with those mobilized with CY alone (P = 0.02). These data confirm the hypothesis that PBPC may be used alone or to augment BM to achieve a timely hematopoietic recovery resulting in shortened hospital stays, decreased transfusion requirements, and decreased antibiotic and amphotericin usage.