Sequential transplants using mobilized peripheral blood progenitor cells

Modest success has been achieved with the use of high-dose cytotoxic therapy and bone marrow transplantation in solid tumors. Patient outcome can potentially be improved with further intensification of the therapy. The rapid hematologic recovery achieved with mobilized peripheral blood progenitor cells (PBPC) may reduce the toxicity of transplantation enabling the use of sequential courses of myeloablative therapy. We report on 42 patients with solid tumors enrolled in a tandem transplant protocol involving the use of PBPC mobilized with cyclophosphamide (4 g/m²), etoposide (1 g/m²), and granulocyte-colony-stimulating factor (G-CSF: 10 μg/kg/day). This regimen significantly increased the number of circulating progenitor cells; only 1-2 aphereses were sufficient to collect 2.5 × 10⁸/kg mononuclear cells, our goal for each transplant course. The median number of circulating colony-forming units (CFU) and CD34+ cells obtained for each transplant course were 70.3 × 10⁴/kg and 11.7 × 10⁶/kg, respectively. There was a significant correlation between the numbers of CD34+ cells and CFU measured in the apheresis product (r = 0.49, P = .003). The first transplant regimen given to 38 patients consisted of thiotepa, carboplatin, and cyclophosphamide. The second transplant regimen given to 29 patients consisted of busulfan and etoposide. Hematologic recovery was comparable after each of the two transplant courses. The median time to neutrophil recovery over 0.5 × 10⁹/L and to platelet transfusion independence was 9 and 8 days, respectively. There was no difference in engraftment rates after transplant with PBPC only (n = 28 courses) compared to transplant with PBPC plus bone marrow (n = 39 courses). There was a significant correlation between hematologic recovery after transplant and the number of CD34+ cells present in the PBPC. In conclusion, 1) PBPC are significantly mobilized with this combination chemotherapy and G-CSF, 2) mobilized PBPC result in rapid engraftment after myeloablative therapy, 3) hematologic recovery rates are comparable after sequential PBPC transplants, 4) PBPC alone are sufficient for long-term engraftment, and 5) rapid engraftment after PBPC transplant enables the use of a second course of myeloablative therapy within a short interval of time.