IN-VIVO EFFECTS OF GM-CSF AND IL-3 ON HEMATOPOIETIC-CELL RECOVERY IN BONE-MARROW AND BLOOD AFTER AUTOLOGOUS TRANSPLANTATION WITH MAFOSFAMIDE-PURGED MARROW IN LYMPHOID MALIGNANCIES

This retrospective study evaluates the impact of GMCSF and interleukin 3 (IL-3) on bone marrow (BM) and peripheral blood (PB) cell recovery following autologous bone marrow transplantation (ABMT) with mafosfami de-purged BM in patients with lymphoid malignancies compared with a co ntrol group receiving no colony-stimulating factor. GM-CSF was adminis tered at 250 mu g/m(2)/day (8 patients) as a continuous infusion from day of autologous BMT until the absolute neutrophil count (ANC) reache d 0.5 x 10(9)/1 for 7 days or until day 30, whichever was first, IL-3 was administered daily starting on the first day of transplant at a do se of 1 mu g/kg/day (6 patients) and 5 mu g/kg/day (6 patients) for 30 days. CFU-GM and BFU-E were sequentially evaluated in BM and PB at da ys 7, 14, 21, 28, and 56 post-graft. The neutrophil recovery (ANC > 0. 5 x 10(9)/1) was significantly faster in the GM-CSF group compared wit h IL-3 5 mu g, IL-3 mu g and control group (respectively, days 15, 21, 22, 24) (p < 0.05 to p < 0.01). Similarly, leukocyte recovery was fas ter in the GM-CSF group compared with control and IL-3 1 mu g groups ( p < 0.01 and p < 0.05). No difference was noticed between the two IL-3 groups. Although no difference was observed in platelet recoveries (> 50 x 10(9)/1), it appeared that the GM-CSF group required more units of platelets than either the IL-3 1 mu g or 5 mu g groups (p < 0.05). The IL-3 1 mu g group required more red cells units than any other gro up (p < 0.05). Faster BM CFU-GM and BFU-E recovery were observed in th e IL-3 1 mu g group compared with all other groups (p < 0.01). However , the GM-CSF group was shown to have a more pronouced circulation of P B CFU-GM following transplantation (p < 0.05) compared with the contro l; no difference was observed between the two IL-3 groups. BM long-ter m culture studies initiated at day 28 post-autologous BMT suggested an alteration of the primitive progenitor compartment in the IL-3 and GM -CSF groups as shown by the weekly behavior of CFU-GM resulting in a d ecreased cumulative production after 8 weeks of culture. In conclusion , these data indicate that different mechanisms of action may be ascri bed to IL-3 and GM-CSF on hemopoietic recovery following autologous BM T with mafosfamide-purged marrow; their potential synergistic effect f avors sequential administration following autologous BMT.