Background/Objectives:Intensive chemotherapy is the cornerstone of lymphoma treatment but often leads to severe chemotherapy-induced thrombocytopenia (sCIT), resulting in treatment delays, reduced dose intensity, and the need for transfusions. While granulocyte colony-stimulating factors (G-CSFs) are commonly used to manage neutropenia, the use of thrombopoietic growth factors has not been adequately studied.Methods:This phase I dose-finding study evaluated the use of weekly romiplostim as prophylaxis for recurrent sCIT in patients undergoing chemotherapy for lymphoma. Eligible patients were those treated with a 21-day chemotherapy cycle who previously experienced sCIT, thus serving as their own “controls”. sCIT was defined as one of the following: (A) a platelet count (PLT) <50 × 109/L on day 1 of the subsequent cycle, leading to delay or dose reduction in chemotherapy, or (B) grade 4 thrombocytopenia (<25 × 109/L) and/or (C) platelet transfusion for bleeding. The primary endpoints were the incidence of sCIT and the rate of romiplostim-associated-adverse-events, with thromboembolic complications being an event of special interest.Results:Nine patients with sCIT requiring a PLT transfusion on the prior treatment cycle were treated across three dose schedules. The phase 2 recommended schedule was defined as a starting dose of 3–5 mcg/kg based on the baseline PLT count, with weekly adjustments for counts <150 × 109/L and >450 × 109/L. Romiplostim prevented recurrent grade 4 thrombocytopenia in 47% of the chemotherapy cycles and averted recurrent transfusion in 65% of cycles. Notably, low starting doses, as used in solid malignancies, were insufficient, leading to recurrent thrombocytopenia.Conclusions:Romiplostim was well-tolerated, with no thromboembolic events, and allowed most patients to complete their chemotherapy on schedule at full dose intensity.
背景/目的：强化化疗是淋巴瘤治疗的基石，但常导致严重的化疗诱导性血小板减少症（sCIT），引发治疗延迟、剂量强度降低及输血需求。虽然粒细胞集落刺激因子（G-CSFs）常用于管理中性粒细胞减少症，但血小板生成生长因子的应用尚未得到充分研究。 方法：这项I期剂量探索研究评估了罗米司亭每周给药方案在淋巴瘤化疗患者中预防复发性sCIT的效果。符合入组标准的患者需接受21天化疗周期治疗且既往发生过sCIT，从而可作为自身“对照”。sCIT定义为满足以下任一条件：（A）后续周期第1天血小板计数（PLT）<50×10⁹/L，导致化疗延迟或减量；或（B）4级血小板减少（<25×10⁹/L）和/或（C）因出血需要输注血小板。主要终点为sCIT发生率及罗米司亭相关不良事件（特别关注血栓栓塞并发症）的发生率。 结果：9例在前期治疗周期中因sCIT需要输注血小板的患者按三种给药方案接受治疗。根据基线PLT计数，II期推荐方案确定为起始剂量3–5微克/千克，并依据每周PLT计数（<150×10⁹/L或>450×10⁹/L）进行调整。罗米司亭在47%的化疗周期中预防了4级血小板减少症的复发，并在65%的周期中避免了再次输血。值得注意的是，实体瘤治疗中使用的低起始剂量不足以预防血小板减少症复发。 结论：罗米司亭耐受性良好，未发生血栓栓塞事件，使大多数患者能够按计划完成全剂量强度的化疗。
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