SEQUENTIAL TRANSPLANTS USING MOBILIZED PERIPHERAL-BLOOD PROGENITOR CELLS

Modest success has been achieved with the use of high-dose cytotoxic t herapy and bone marrow transplantation in solid tumors. Patient outcom e can potentially be improved with further intensification of the ther apy. The rapid hematologic recovery achieved with mobilized peripheral blood progenitor cells (PBPC) may reduce the toxicity of transplantat ion enabling the use of sequential courses of myeloablative therapy. W e report on 42 patients with solid tumors enrolled in a tandem transpl ant protocol involving the use of PBPC mobilized with cyclophosphamide (4 g/m2), etoposide (1 g/m2), and granulocyte-colony-stimulating fact or (G-CSF: 10 mug/kg/day). This regimen significantly increased the nu mber of circulating progenitor cells; only 1-2 aphereses were sufficie nt to collect 2.5 x 10(8)/kg mononuclear cells, our goal for each tran splant course. The median number of circulating colony-forming units m ononuclear cells, our goal for each transplant course. The median 10(4 )/kg and 11.7 x 10(6)/kg, respectively. There was a significant correl ation between the numbers of CD34 + cells and CFU measured in the aphe resis product (r = 0.49, P = .003). The first transplant regimen given to 38 patients consisted of thiotepa, carboplatin, and cyclophosphami de. The second transplant regimen given to 29 patients consisted of bu sulfan and etoposide. Hematologic recovery was comparable after each o f the two transplant courses. The median time of neutrophil recovery o ver 0.5 x 10(9)/L and to platelet transfusion indenpendence was 9 and 8 days, respectively. There was no difference in engraftment rates aft er transplant with PBPC only (n = 28 courses) compared to transplant w ith PBPC plus bone marrow (n = 39 courses). There was a significant co rrelation between hematologic recovery after transplant and the number of CD34+ cells present in the PBPC. In conclusion, 1) PBPC are signif icantly mobilized with this combination chemotherapy and G-CSF, 2) mob ilized PBPC result in rapid engraftment after myeloablative therapy, 3 ) hematologic recovery rates are comparable after sequential PBPC tran splants, 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. (C) 1 994 Wiley-Liss, Inc.