SYNERGISTIC EFFECTS OF THROMBOPOIETIN AND GRANULOCYTE-COLONY-STIMULATING FACTOR ON NEUTROPHIL RECOVERY IN MYELOSUPPRESSED MICE

Severe suppression of the hematopoietic system is a major factor in li miting chemotherapy dose escalation. To determine whether a combinatio n of human recombinant granulocyte colony-stimulating factor (G-CSF) a nd thrombopoietin (TPO) would alter recovery of platelets, red blood c ells (RBCs), or neutrophils after myeloablative therapy, myelosuppress ed mice were treated with sc injections of TPO (90 mu g/kg), G-CSF (25 0 mu g/kg), TPO plus G-CSF or vehicle and complete blood counts were m easured, Marrow and spleen cells were obtained at Various times and as sayed for erythroid, myeloid, and megakaryocytic progenitors. The prol onged neutropenia in vehicle controls (14 days) was significantly shor tened in mice treated with G-CSF or TPO for 14 days. The combination o f TPO plus G-CSF further reduced the duration of neutropenia. TPO and TPO plus G-CSF treatments also significantly shortened thrombocytopeni a compared to vehicle. Recovery of RBCs was also enhanced in mice trea ted with either G-CSF or TPO, or the combination. Furthermore, treatme nt with G-CSF and/or TPO hastened myeloid, erythroid, and megakaryocyt e progenitor recovery compared to vehicle controls. These results show that the combination of TPO plus G-CSF acts synergistically to accele rate neutrophil recovery in myelosuppressed mice and does not compromi se the platelet or RBC response to TPO therapy. (C) 1996 by The Americ an Society of Hematology.