Stahel R A, Jost L M, Cerny T, Pichert G, Honegger H, Tobler A, Jacky E, Fey M, Platzer E
Department of Medicine, University Hospital, Zürich, Switzerland.
J Clin Oncol. 1994 Sep;12(9):1931-8. doi: 10.1200/JCO.1994.12.9.1931.
The aim of this prospective randomized trial was to examine the efficacy and safety of filgrastim after high-dose chemotherapy and autologous bone marrow transplantation (ABMT).
Patients with poor-risk non-Hodgkin's lymphoma or relapsed Hodgkin's disease were treated in a randomized, open-label trial to study the use of filgrastim as an adjunct to high-dose chemotherapy and ABMT. Of 43 assessable patients, 19 were randomized to receive filgrastim by continuous subcutaneous infusion at a dose of 10 micrograms/kg/d, 10 to filgrastim 20 micrograms/kg/d, and 14 to a parallel control group that received no filgrastim after ABMT.
For all filgrastim-treated patients analyzed together, the median time to neutrophil recovery > or = 0.5 x 10(9)/L after the day of ABMT was significantly accelerated to 10 days compared with 18 days in control patients (P = .0001). The median number of platelet transfusions was identical in both groups. Clinical parameters, including the median number of days with fever (1 v 4, P = .0418) and neutropenic fever (5 v 13.5, P = .0001) were significantly shorter in the filgrastim than in the control group. The number of days on intravenous antibiotics and duration of hospitalization were also shorter in the treated groups; however, the differences did not reach statistical significance. For patients treated with the two different dose levels of filgrastim, the neutrophil recovery and clinical results were similar. Filgrastim-associated toxicity appeared to be minimal, with five adverse events considered at least possibly related to filgrastim: two in the higher-dose group and three in the lower-dose group. All of these were rated moderate, except one case of severe bone pain that did not preclude continued filgrastim treatment at a lower dose. Survival and relapse-free survival were similar for control and filgrastim-treated patients.
Taken together, the results of this first randomized study support the role of filgrastim given as an adjunct to ABMT in accelerating neutrophil recovery, as well as in reducing treatment-related morbidity and overall duration of the treatment procedure.
这项前瞻性随机试验的目的是研究高剂量化疗及自体骨髓移植（ABMT）后使用非格司亭的疗效和安全性。
对预后不良的非霍奇金淋巴瘤或复发性霍奇金病患者进行了一项随机、开放标签试验，以研究非格司亭作为高剂量化疗及ABMT辅助治疗的应用。在43例可评估患者中，19例被随机分配接受皮下持续输注非格司亭，剂量为10微克/千克/天，10例接受非格司亭20微克/千克/天，14例被分配至平行对照组，ABMT后不接受非格司亭治疗。
对所有接受非格司亭治疗的患者进行综合分析，ABMT后中性粒细胞恢复至≥0.5×10⁹/L的中位时间显著加快至10天，而对照组患者为18天（P = 0.0001）。两组的血小板输注中位数相同。包括发热天数中位数（1天对4天，P = 0.0418）和中性粒细胞减少性发热天数中位数（5天对13.5天，P = 0.0001）在内的临床参数，非格司亭组明显短于对照组。治疗组静脉使用抗生素的天数和住院时间也较短；然而，差异未达到统计学意义。对于接受两种不同剂量水平非格司亭治疗的患者，中性粒细胞恢复情况和临床结果相似。非格司亭相关毒性似乎极小，有5例不良事件被认为至少可能与非格司亭有关：高剂量组2例，低剂量组3例。除1例严重骨痛病例外，所有这些事件的严重程度均为中度，该严重骨痛病例并未妨碍以较低剂量继续使用非格司亭治疗。对照组和接受非格司亭治疗患者的生存率和无复发生存率相似。
总体而言, 这项首次随机研究的结果支持非格司亭作为ABMT辅助治疗在加速中性粒细胞恢复以及降低治疗相关发病率和缩短治疗总疗程方面的作用。
