THE EFFECT OF MACROPHAGE COLONY-STIMULATING FACTOR ON HEMATOPOIETIC RECOVERY AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION

Macrophage colony-stimulating factor (M-CSF) is active in the late stages of monocyte maturation, activates mature monocyte-macrophages and enhances their production of various other cytokines. We have examined the effects of a 21 d course of escalating doses of M-CSF purified from human urine (hM-CSF) on recovery following autologous bone marrow transplantation (ABMT) in 20 patients with malignant lymphomas. Four patients were treated at each dose level of 4, 8, 16, 32 and 64 x 10(6) U/m2/d and results compared to 46 concurrent controls. There was no significant difference in recovery to an absolute neutrophil count (ANC) of 0.5 x 10(9)/l (median 20 d in hM-CSF group versus 22 in controls) or in recovery of platelets to 50 x 10(9)/l (32 d versus 39 d, 0.05<P<0.1); hM-CSF patients received a median of 81 platelet units following ABMT (controls 112 units, P=NS). hM-CSF patients had a median of 5.5 d with fever >37.5-degrees-C (control 8, P=NS), received parenteral antibiotics for 14.5 d (control 17, P=NS) and had a 50% incidence of bacteraemia (control 48%). hM-CSF treated patients were discharged by a median of day 29 following transplantation (control 33, P<0.05). Platelet and neutrophil recovery correlated significantly with the number of marrow mononuclear cells (MNC) reinfused in the hM-CSF group (P=0.05 and P=0.014 respectively) but not in controls. Subgroup analysis showed that hM-CSF patients receiving >2 x 10(8) MNC/kg body weight reached an ANC of 0.5 x 10(9)/1 by a median of day 16.5 (control 18.5, NS). became platelet transfusion independent by day 17 (control 29, P<0.05) and reached a platelet count of 50 x 10(9)/l by day 21 (control 40, P<0.05). No significant toxicity attributable to hM-CSF treatment was seen. These results suggest that hM-CSF accelerates platelet recovery following ABMT and that relatively large marrow innocula are required to see this effect.