Utilization of recombinant human GM-CSF to enhance peripheral progenitor cell yield for autologous transplantation

Evidence has accumulated which indicates that efficacy of chemotherapy correlates with dose intensity and with total dose. For most cytotoxic agents, the major limiting factor for escalation of dose intensity is myelotoxicity. Attempts have been made to circumvent myelotoxicity by autologous bone marrow transplantation. Recently, it has been demonstrated that progenitors enriched from the peripheral blood can also be used successfully for autografting. The concentration of progenitor cells in peripheral blood is lower than that in bone marrow but myelosuppressive chemotherapy or hematopoietic growth factors, or a combination of both can be exploited to enhance the progenitor cell yield. The studies reported here are sequential. In the first study, eight patients with advanced Hodgkin's disease received myelosuppressive regimen consisting of cytarabine (100 mg/m2/12h SC days 1 to 5) and daunorubicin (45 mg/m2/d, days 3 and 4). Progenitor cell leukapheresis was performed during the rebound phase of hematopoiesis. All eight patients were treated with super-dose chemotherapy with progenitor cell transplantation. One patient died of CNS toxicity 48 days after transplantation but all other seven had sustained engraftment. In the second study, human recombinant GM-CSF (at 250 micrograms/m2/d as continuous infusion) was administered to twelve patients. Leukapheresis was started at a white blood count (WBC) of greater than 10 x 10(9)/L and the dosage of rhGM-CSF adjusted to keep the WBC between 10 x 10(9)/L and 20 x 10(9)/L. The median duration of rhGM-CSF application was 11.5 days and a median number of six leukaphereses performed. The median increase in the number of granulocyte-macrophage colony forming units (CFU-GM)/ml of peripheral blood was 8.5 fold.(ABSTRACT TRUNCATED AT 250 WORDS)