Bussel J B, Mukherjee R, Stone A J
Weill Medical College of Cornell University-New York Presbyterian Hospital, Division of Pediatric Hematology-Oncology, New York, New York 10021, USA.
Am J Hematol. 2001 Mar;66(3):172-7. doi: 10.1002/1096-8652(200103)66:3<172::aid-ajh1041>3.0.co;2-q.
The objective of this research was to determine whether rhuIL-11 is an effective treatment in patients with refractory immune thrombocytopenic purpura (ITP). Platelet production is decreased in certain cases of refractory ITP. IL-11 stimulates megakaryocytopoiesis in vitro and was licensed for its clinical effects to ameliorate chemotherapy-induced thrombocytopenia. A pilot study was initiated, intending to enroll 12 patients with ITP. These patients were to receive rhuIL-11 (Neumega) at a dose of 50 microg/kg subcutaneously daily for 21 consecutive days and be observed afterward for 21 additional days. CBC with platelets were obtained twice weekly with visits and physical examinations weekly. The study was terminated after 7 patients were enrolled because of toxicity and lack of efficacy. All 7 patients had had ITP for >9 years and had failed splenectomy, intravenous gammaglobulin, corticosteroids, and a variety of other treatments. The patients at entry all had platelet counts <20,000/microl; 5 of 7 had counts <10,000/microl. The maximal median increase for any day of the study was 6,000/microl. No patient achieved a count of 30,000/microl, and only 3 patients achieved (once each) a platelet count >20,000/microl. Substantial toxicity was seen. The nadir hemoglobin decrease was a mean of 2 g/dl. rhuIL-11 was not effective at increasing the platelet count in any of these patients with refractory ITP. Toxicity was substantial. The lack of platelet response to rhuIL-11 in this study does not exclude the possibility of better effects at other doses and/or in less refractory patients.
本研究的目的是确定重组人白细胞介素-11（rhuIL-11）对难治性免疫性血小板减少性紫癜（ITP）患者是否为一种有效的治疗方法。在某些难治性ITP病例中，血小板生成减少。白细胞介素-11在体外可刺激巨核细胞生成，并且已因其改善化疗所致血小板减少症的临床疗效而获得许可。一项试点研究启动，计划招募12例ITP患者。这些患者将连续21天每天皮下注射剂量为50μg/kg的rhuIL-11（Neumega），之后再观察21天。每周就诊两次时检测全血细胞计数及血小板，每周进行体格检查。在招募了7例患者后，由于毒性和缺乏疗效，该研究终止。所有7例患者患ITP均超过9年，且脾切除术、静脉注射丙种球蛋白、皮质类固醇及其他多种治疗均无效。入组时所有患者的血小板计数均<20,000/μl；7例中有5例计数<10,000/μl。研究中任何一天的最大中位数增幅为6,000/μl。没有患者的血小板计数达到30,000/μl，只有3例患者（各有一次）的血小板计数>20,000/μl。观察到明显的毒性。血红蛋白最低点平均下降2g/dl。rhuIL-11对任何难治性ITP患者均未能有效提高血小板计数。毒性很大。本研究中血小板对rhuIL-11无反应并不排除在其他剂量和/或病情较轻的患者中可能有更好疗效的可能性。
