Passamonti Francesco, Lazzarino Mario
Division of Hematology, University of Pavia, IRCCS Policlinico San Matteo, Viale Golgi 19, 27100, Pavia, Italy.
Leuk Lymphoma. 2003 Sep;44(9):1483-8. doi: 10.3109/10428190309178768.
Pipobroman (PB) is a neutral amide of piperazine with a chemical structure close to that of alkylating agents, although the exact mechanism of action of PB has not been demonstrated. PB has well documented clinical activity in polycythemia vera (PV) and essential thrombocythemia (ET). Recent long-term follow-up studies on PV and ET patients receiving PB have facilitated the definition of the risk of late transformation into myelofibrosis with myeloid metaplasia (MMM) or acute leukemia (AL). This report gives an overview of the treatment with PB in patients with PV and ET focusing on clinical activity, administration dose and schedule, toxicity, impact on short- and long-term complications. From our experience and from the data reported in the literature the high clinical activity of PB in both PVand ET becomes evident. This drug allows, within 3 months, to attain a response in more than 90% of patients, without clinically relevant toxicities. The 10-years risk of thrombosis of patients treated with PB is about 15%, similar to that registered with hydroxyurea, the most widely used agent in PVand ET. The antiproliferative activity of PB on bone marrow megakaryocytes seems of particular value in lowering the occurrence of post-PV and post-ET MMM, whose risk (< 4% at 10 years) is the lowest registered with available treatments. The 10-year risk of acute leukemia with PB is 5% in PVand 3% in ET, which is only slightly higher than that expected as a natural evolution of the disease. In conclusion, the use of PB is a definite alternative to hydroxyurea in patients with PV and ET at high risk of thrombosis.
哌泊溴烷（PB）是一种哌嗪的中性酰胺，其化学结构与烷化剂相近，尽管PB的确切作用机制尚未阐明。PB在真性红细胞增多症（PV）和原发性血小板增多症（ET）中具有充分记录的临床活性。近期对接受PB治疗的PV和ET患者的长期随访研究，有助于明确晚期转化为骨髓纤维化伴髓外化生（MMM）或急性白血病（AL）的风险。本报告概述了PB治疗PV和ET患者的情况，重点关注临床活性、给药剂量和方案、毒性以及对短期和长期并发症的影响。根据我们的经验以及文献报道的数据，PB在PV和ET中均具有很高的临床活性这一点显而易见。这种药物能在3个月内使超过90%的患者产生反应，且无临床相关毒性。接受PB治疗的患者10年血栓形成风险约为15%，与PV和ET中使用最广泛的药物羟基脲的风险相似。PB对骨髓巨核细胞的抗增殖活性，在降低PV和ET后MMM的发生率方面似乎具有特别价值，其风险（10年时<4%）是现有治疗中记录到的最低风险。PV患者使用PB后急性白血病的10年风险为5%，ET患者为3%，仅略高于该疾病自然发展预期的风险。总之，对于有高血栓形成风险的PV和ET患者，使用PB是羟基脲的明确替代方案。
