Gajewski James L, Rondon Gabriela, Donato Michele L, Anderlini Paolo, Korbling Martin, Ippoliti Cindy, Benyunes Mark, Miller Langdon L, LaTemple Denise, Jones Denny, Ashby Mark, Hellmann Sue, Durett April, Lauppe Jo, Geisler Deborah, Khouri Issa F, Giralt Sergio A, Andersson Borje, Ueno Naoto T, Champlin Richard
University of Texas M. D. Anderson Cancer Center, Department of Blood and Marrow Transplantation, Houston 77030-4095, USA.
Biol Blood Marrow Transplant. 2002;8(10):550-6. doi: 10.1053/bbmt.2002.v8.pm12434950.
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 microg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 microg/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 > or = 2 x 10(9)/L; leukapheresis was continued until acquisition of a target dose of > or = 5 x 10(6) 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 x 10(6) CD34 cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 x 10(6) cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34+ cells. When PBPCs were infused after high-dose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 x 10(9)/L and a platelet count of 20 x 10(9)/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.
这项I/II期剂量递增研究检测了重组人血小板生成素（rhTPO）和粒细胞集落刺激因子（G-CSF）对晚期乳腺癌患者化疗后动员外周血祖细胞（PBPCs）的安全性和有效性。患者接受环磷酰胺、依托泊苷和顺铂（CVP）治疗，随后接受G-CSF（6微克/千克，每日两次）和rhTPO（0.6、1.2、2.4或3.6微克/千克，于化疗后第5天单次给药，或于化疗后第5、7和9天分3次给药）。当最低点后白细胞计数达到≥2×10⁹/L时，通过每日白细胞分离术采集PBPCs；白细胞分离术持续进行，直至采集到目标剂量≥5×10⁶个CD34⁺细胞/千克。动员的PBPCs在接受环磷酰胺、卡莫司汀和噻替派（CBT）的额外高剂量化疗后移植入患者体内。将其与同期接受相同化疗方案和G-CSF支持但未接受rhTPO的非随机对照患者进行比较。在32例接受CVP后接受rhTPO和G-CSF的可评估患者中，91%仅需1次白细胞分离术即可获得目标PBPC移植物；相比之下，36例对照患者中只有69%通过1次白细胞分离术达到目标移植物（P = 0.026）。接受rhTPO治疗的患者每次白细胞分离术获得的CD34细胞中位数为26.7×10⁶/千克，而对照组为11.5×10⁶/千克（P = 0.09）。较高剂量的rhTPO似乎能产生更多的CD34⁺细胞。在高剂量CBT化疗后输注PBPCs时，绝对中性粒细胞计数恢复至0.5×10⁹/L和血小板计数恢复至20×10⁹/L的中位时间分别为15天和16天；这些值与对照组（中性粒细胞和血小板均为15天）无差异。没有患者产生抗TPO抗体。这些结果表明，rhTPO能安全有效地增加化疗和G-CSF动员的PBPCs数量，并可减少所需的白细胞分离术次数。对于使用现有技术治疗时可能出现PBPC动员不佳的患者，也有必要进行进一步研究。
