Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan.
Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan.
Transplantation. 2024 Apr 1;108(4):996-1003. doi: 10.1097/TP.0000000000004880. Epub 2024 Mar 23.
Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem cell (PBSC) mobilization in healthy volunteers. However, data on the adequate dose of pegfilgrastim for PBSC mobilization are limited. This phase 2, single-arm study evaluated the efficacy and safety of pegfilgrastim for PBSC mobilization in healthy volunteers.
The study comprised 2 phases: pilot (steps 1-3, dose escalation, a single subcutaneous dose of 3.6, 7.2, and 10.8 mg pegfilgrastim, respectively) and evaluation (step 4, efficacy and safety assessments). The primary endpoint was the proportion of subjects who achieved mobilization of ≥20 × 10 6 /L cluster of differentiation 34 positive (CD34 + ) cells.
Thirty-five subjects (6 each in steps 1 and 2 and 23 in step 4) were included. In the pilot phase, step 3 with a 10.8 mg dose was not conducted due to favorable outcomes in step 2 (desired CD34 + cell count), at 7.2 mg pegfilgrastim, which was identified as the optimal dose for the evaluation phase. In the evaluation phase, successful CD34 + mobilization was achieved in all 23 subjects. The mean peripheral blood CD34 + cells count peaked on day 5. Back pain, thrombocytopenia, transient elevations of alkaline phosphatase, and lactate dehydrogenase were the most common adverse events. All adverse events were mild, and none led to study discontinuation.
A single-dose pegfilgrastim successfully mobilized an optimal number of CD34 + cells and was well tolerated. Pegfilgrastim could be an alternative option for PBSC mobilization in healthy volunteers. The trial was registered at www.clinicaltrials.gov (NCT03993639).
培非格司亭是一种长效粒细胞集落刺激因子，具有方便的单次注射剂量，正在被研究用于健康志愿者的外周血造血干细胞（PBSC）动员。然而，关于培非格司亭用于 PBSC 动员的适当剂量的数据有限。这项 2 期、单臂研究评估了培非格司亭用于健康志愿者 PBSC 动员的疗效和安全性。
该研究包括 2 个阶段：试验（步骤 1-3，剂量递增，分别给予单剂量 3.6、7.2 和 10.8mg 培非格司亭）和评估（步骤 4，疗效和安全性评估）。主要终点是达到动员≥20×10 6 /L 细胞分化抗原 34 阳性（CD34 + ）细胞的受试者比例。
共纳入 35 名受试者（步骤 1 和 2 各 6 名，步骤 4 共 23 名）。在试验阶段，由于步骤 2 中 7.2mg 培非格司亭的结果有利（期望的 CD34 + 细胞计数），没有进行步骤 3（10.8mg 剂量）。7.2mg 培非格司亭被确定为评估阶段的最佳剂量。在评估阶段，所有 23 名受试者均成功动员 CD34 + 。外周血 CD34 + 细胞计数于第 5 天达到峰值。背痛、血小板减少症、碱性磷酸酶和乳酸脱氢酶的短暂升高是最常见的不良事件。所有不良事件均为轻度，无研究中断。
单次剂量的培非格司亭成功动员了最佳数量的 CD34 + 细胞，且耐受性良好。培非格司亭可能是健康志愿者 PBSC 动员的另一种选择。该试验在 www.clinicaltrials.gov 注册（NCT03993639）。
