CM-CSF INSTEAD OF HEMATOLOGICAL SUPPORT DURING HIGH-DOSE CHEMOTHERAPY FOR REFRACTORY MALIGNANT-LYMPHOMA

Patients with refractory malignant lymphoma (RML) have a poor prognosis when treated with conventional chemotherapy. The use of high-dose chemotherapy has been limited by secondary myelosuppression. We report the use of intensive and short-duration chemotherapy in patients with RML who received granulocyte-macrophage colony-stimulating factor (GM-CSF) instead of hematological support and salvage with bone marrow transplantation or infusion of peripheral blood stem cells. Thirty-one patients with RML were treated with cyclophosphamide: 7 g/m(2), iv on day 1, followed by GM-CSF: 5 mu g/kg/day, subcutaneously until hematological recovery (granulocytes > 1.8 x 10(9)/L) started on day 2. Methotrexate, 5 g/m(2), was also given when the granulocytes and platelets counts were normal, followed by leucovorin rescue. Epirubicin, 180 mg/m(2), iv, was given on day 29 if the granulocyte count was normal, and GM-CSF was started on day 30. Complete response was obtained in 21 out of 31 patients (67%) and partial response in 4 more, thus an overall response was achieved in 80% of the treated patients. Time to treatment failure was 24+ months, and the overall survival was 28+ months. Hematological toxicity grade IV, according to the WHO criteria was observed in all cycles, however hematological recovery was already evident on day 13 +/- 2. Eleven patients developed infection related to the treatment, but no therapy related death was observed. GM-CSF was well tolerated with minimal toxicity. Is evident that GM-CSF can act as hematological support after high-dose chemotherapy in patients who cannot undergo bone marrow transplantation programs. We feel that the use of colony-stimulating factors instead of bone marrow support should be explored in more controlled clinical trials and that high-dose chemotherapy should be considered as primary treatment in patients with poor prognosis non-Hodgkin's lymphoma.