Haematological recovery following high-dose cyclophosphamide with autologous bone marrow transplantation

Abstract

A total of 31 patients with previously untreated small-cell carcinoma of the lung were treated with very-high-dose cyclophosphamide, using autologous bone marrow transplantation (ABMT) to assist haematological recovery. The period of neutropenia was shorter with 40 mg/kg cyclophosphamide x 4 (7 patients) than when the dose of cyclophosphamide was increased to 50 mg/kg x 4 (11 patients), despite ABMT 2 days after chemotherapy in each group. In all, 13 patients were treated with 50 mg/kg cyclophosphamide x 4, with infusion of bone marrow delayed to day 4, 6 or 8 after chemotherapy to determine the contribution of ABMT to haematological recovery. The period of neutropaenia was increased when marrow was returned 6 days following chemotherapy, confirming that ABMT contributed to haematological recovery after this schedule of treatment. A total of 11 patients had a second cycle of 50 mg/kg cyclophosphamide x 4 after recovery from the first cycle of high-dose chemotherapy. The period of myelosuppression was greater with the second cycle of chemotherapy, although ABMT was carried out during both cycles. The results show that ABMT contributes to haematological recovery when the dose of cyclophosphamide is high enough to produce prolonged hypoplasia. The increased myelosuppression observed after a second high-dose treatment in spite of ABMT suggests either that both transplanted and endogenous marrow activity contribute to recovery of myelopoiesis or that there is residual damage to marrow stroma after the first cycle of treatment. The data indicate the necessity of carefully assessing the role of ABMT in haematological recovery with high-dose chemotherapy regimens.