CONCURRENT PARTIAL BODY RADIATION PREVENTS CYTOKINE MOBILIZATION OF BLOOD PROGENITOR CELLS - AN EFFECT MEDIATED BY A CIRCULATING FACTOR

Mobilization of stem and progenitor cells into blood, which facilitate s the collection of blood-derived autograft and allograft products, ca n be accomplished with administration of myelosuppressive chemotherapy , hematopoietic growth factors, or both. Autologous donor indifference to mobilization attempts has been correlated with prior administratio n of chemotherapy and radiation therapy. To investigate whether concur rent administration of radiation therapy inhibits mobilization, five d aily injections of a potent combination of mobilizing cytokines, 500 U /kg erythropoietin (EPO) plus 15 mu g/kg G-CSF, were administered each morning to Balb/c mice. Each afternoon, a 2 Gy fraction of Co-60 radi ation was administered to either the lower limb or the upper or lower hemibody. Each day, mice were necropsied, and blood stem cell mobiliza tion was determined by assaying the number of hematopoietic colony-for ming cells in the blood and in the spleen. Unirradiated cytokine-injec ted mice showed a significant mobilization effect evident as increased colony-forming cells in blood and spleen compared with saline-injecte d unirradiated controls. The irradiated mice showed markedly inhibited or absent mobilization regardless of the part of the body irradiated. To investigate the mechanism of radiation-induced mobilization inhibi tion, heparinized plasma was obtained from mice whose lower bodies wer e irradiated with 2 Gy 18 h previously, and 0.5 ml was injected i.v. i nto intact mice 10 min before they received 15 mu g/kg G-CSF and 500 U /kg EPO. Unlike mice that received G-CSF + EPO only and showed mobiliz ation of progenitors from marrow to spleen, recipients of plasma from irradiated mice before and after cytokine administration showed signif icantly reduced mobilization of progenitors. Thus, radiation-induced i nhibition of stem cell mobilization is mediated by an unidentified cir culating factor.