Recombinant human thrombopoietin in combination with granulocyte colony-stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy

Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy R ecombinant human thrombopoietin (rhTPO) may further increase the progenitor -cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granu locyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treat ed with high-dose chemotherapy followed by PBPC reinfusion. Initially, pati ents received escalating single doses of rhTPO intravenously (IV) at 0.6, 1 .2, or 2.4 pg/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 m u g/kg on days -3, -1, and 1, or 0.6 mu g/kg on days -1 and 1. G-CSF, 5 mu g/kg IV or subcutaneously (SC) twice daily, was started on day 3 and contin ued through aphereses. Twenty comparable, concurrently and identically trea ted patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as compar isons. CD34(+) cell yields were substantially higher with the first apheres is following rhTPO and G-CSF versus G-CSF alone: 4.1 x 10(6)/kg (range, 1.3 to 17.6) versus 0.8 x 10(6)/kg (range, 0.3 to 4.2), P = .0003. The targete d minimum yield of 3 x 10(6) CD34+ cells/kg was procured following a single apheresis procedure in 61% of the rhTPO and G-CSF-mobilized group versus 1 0% of G-CSF-mobilized patients (P =.001). In rhTPO and G-CSF mobilized pati ents, granulocyte (day 8 v 9, P = .0001) and platelet recovery (day 9 v 10, P = .07) were accelerated, and fewer erythrocyte (3 v 4, P = .02) and plat elet (4 v 5, P = .02) transfusions were needed compared with G-CSF-mobilize d patients. Peripheral blood platelet counts, following rhTPO and G-CSF, we re increased by greater than 100% and the platelet content of PBPC products by 60% to 110% on the first and second days of aphereses (P < .0001) with the greatest effect seen with repeated dosing of rhTPO at 0.6 mu g/kg, rhTP O is safe and well tolerated as a mobilizing agent before PBPC collection. Mobilization with rhTPO and G-CSF, in comparison to a comparable, nonrandom ized G-CSF-mobilized group of patients, decreases the number of apheresis p rocedures required, may accelerate hematopoietic recovery, and may reduce t he number of transfusions required following high-dose chemotherapy for bre ast cancer. (C) 1999 by The American Society of Hematology.