Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor peripheral blood progenitor cell mobilization

This phase I/II dose-escalation study examined the safety and efficacy of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (G-CSF) for postchemotherapy mobilization of peripheral blood progenitor cells (PBPCs) in patients with advanced breast cancer. Patients received cyclophosphamide, etoposide, and cisplatin (CVP) followed by G-CSF (6 μg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 μg/kg as a single dose on day 5 or as 3 doses on days 5, 7, and 9 after chemotherapy). PBPCs were collected by daily leukapheresis when the postnadir white blood cell count reached ≥2 × 10⁹/L; leukapheresis was continued until acquisition of a target dose of ≥5 × 10⁶ CD34⁺ cells/kg. Mobilized PBPCs were transplanted into patients after additional high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa (CBT). Comparisons were made with contemporaneously treated, nonrandomized, control patients who received the same chemotherapy regimens and G-CSF support but who did not receive rhTPO. Of 32 evaluable patients receiving rhTPO and G-CSF after CVP, 91% required only 1 leukapheresis to achieve a target PBPC graft; by contrast, only 69% of 36 of the control patients achieved the target graft with just 1 leukapheresis (P = .026). A median of 26.7 × 10⁶ CD34⁺ cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 × 10⁶ cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34⁺ cells. When PBPCs were infused after highdose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 × 10⁹/L and a platelet count of 20 × 10⁹/L were 15 and 16 days, respectively; these values did not differ from those in the control group (15 days for both neutrophil and platelets). No patient developed anti-TPO antibodies. These results indicate that rhTPO safely and effectively augments the number of PBPCs mobilized with chemotherapy and G-CSF and can reduce the required number of leukaphereses. Further studies are also warranted in patients who are likely to experience suboptimal PBPC mobilization when treated with currently available techniques.