Bargetzi M J, Gluckman E, Tichelli A, Devergie A, Esperou H, Kabata J, Wodnar-Filipowicz A, Nissen C, Speck B, Gratwohl A
Department of Internal Medicine, Kantonsspital Basel, Switzerland.
Br J Haematol. 1995 Oct;91(2):306-12. doi: 10.1111/j.1365-2141.1995.tb05294.x.
In a prospective open-labelled phase I/II trial we tested efficacy and tolerability of recombinant human interleukin-3 (rhIL-3) alone in patients with refractory severe aplastic anaemia (SAA). 15 patients with idiopathic (12 patients) or secondary (one post-hepatitic, one drug induced, one dyskeratosis congenita) SAA, refractory or relapsing after one to three courses of antilymphocyte globulin were included. 14 patients were transfusion dependent (RBC 14, platelet 12). RhIL-3 was planned for three patients each at five escalating dose levels of 1, 2, 4, 8 and 16 micrograms/kg, given daily as 24 h continuous infusion for 21 d. RhIL-3 was prematurely withdrawn at days 10 and 11 for adverse events in two patients. 9/15 patients showed an increase in WBC; 2/6 at the 1-2 micrograms/kg and 7/9 at the 4-16 micrograms/kg level, but no sustained effects were seen. No patient showed a response in platelet counts. Additionally, platelet and RBC transfusion requirements were unchanged pre and post study. All patients experienced one or more adverse event, mainly fever (15 patients), bleeding (nine patients), and headache (six patients). Occurrence of adverse events was dose related and the maximum tolerated dose was reached with 8 micrograms/kg. Five patients suffered serious adverse events. RhIL-3 as single growth factor and used alone is of minimal benefit in severe aplastic anaemia.
在一项前瞻性开放标签的I/II期试验中，我们单独测试了重组人白细胞介素-3（rhIL-3）对难治性严重再生障碍性贫血（SAA）患者的疗效和耐受性。纳入了15例特发性（12例）或继发性（1例肝炎后、1例药物诱导、1例先天性角化不良）SAA患者，这些患者在接受一至三个疗程的抗淋巴细胞球蛋白治疗后难治或复发。14例患者依赖输血（红细胞14例，血小板12例）。计划对1、2、4、8和16微克/千克这五个递增剂量水平的rhIL-3各治疗3例患者，每天24小时持续输注，共21天。两名患者因不良事件在第10天和第11天提前停用rhIL-3。9/15例患者白细胞计数增加；1-2微克/千克剂量水平的2/6例患者和4-16微克/千克剂量水平的7/9例患者出现白细胞增加，但未见持续效果。没有患者血小板计数有反应。此外，研究前后血小板和红细胞输血需求未变。所有患者均经历了一种或多种不良事件，主要是发热（15例）、出血（9例）和头痛（6例）。不良事件的发生与剂量相关，最大耐受剂量为8微克/千克。5例患者发生严重不良事件。rhIL-3作为单一生长因子单独使用对严重再生障碍性贫血益处极小。
