Samuelsson Jan, Hasselbalch Hans, Bruserud Oystein, Temerinac Snezana, Brandberg Yvonne, Merup Mats, Linder Olle, Bjorkholm Magnus, Pahl Heike L, Birgegard Gunnar
Department of Medicine, Stockholm South Hospital, Stockholm, Sweden, and Department of Medicine, Roskilde University Hospital, Denmark.
Cancer. 2006 Jun 1;106(11):2397-405. doi: 10.1002/cncr.21900.
Conventional interferon-alpha (IFN) is an effective treatment for patients with myeloproliferative disorders. However, many patients discontinue therapy because of side effects.
In this 24-month, Phase II feasibility study of pegylated interferon alpha-2b (PEG-IFN) treatment, a starting dose of 0.5 microg/kg per week was received by 21 patients with polycythemia vera (PV) and 21 patients with essential thrombocythemia (ET). The treatment objective, a complete platelet response (CR), was a platelet count<400x10(9)/L in symptomatic patients and <600 in asymptomatic patients. Neutrophil polycythemia rubra vera-1 (PRV-1) messenger RNA expression was analyzed prior to and during therapy. Quality of life (QoL) was investigated by using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire.
At 6 months, 29 of 42 patients (69%) had achieved a CR after a median of 83 days. The CR rate was not related to diagnosis, gender, or previous therapy. Nineteen patients completed the planned 2-year treatment in CR. No thromboembolic or bleeding complications were observed. Phlebotomy requirements were reduced in the majority of patients with PV. Five of 14 patients (36%) who initially were positive for PRV-1 achieved normalized PRV-1 expression under PEG-IFN treatment. Side effects were the cause of therapy failure in 16 of 23 patients. However, only 8 of 19 patients reported any side effects at 2 years. The QLQ-C30 revealed clinically significant impairments in several aspects of QoL at 6 months; however, at 2 years, QoL measurements were not different from baseline.
PEG-IFN effectively reduced platelet counts in 29 of 42 patients, but only 19 patients maintained a CR at 2 years. The reversal of PRV-1 positivity noted in a subset of patients suggested that PEG-IFN may have an effect on the malignant clone. PEG-IFN is a valuable therapeutic alternative for patients who tolerate its initial side effects.
传统的α干扰素（IFN）是治疗骨髓增殖性疾病患者的一种有效方法。然而，许多患者因副作用而中断治疗。
在这项为期24个月的聚乙二醇化α-2b干扰素（PEG-IFN）治疗的II期可行性研究中，21例真性红细胞增多症（PV）患者和21例原发性血小板增多症（ET）患者接受了每周0.5μg/kg的起始剂量治疗。治疗目标是完全血小板反应（CR），即有症状患者的血小板计数<400×10⁹/L，无症状患者<600×10⁹/L。在治疗前和治疗期间分析中性粒细胞真性红细胞增多症-1（PRV-1）信使核糖核酸表达。使用欧洲癌症研究与治疗组织QLQ-C30问卷调查生活质量（QoL）。
6个月时，42例患者中有29例（69%）在中位83天后达到CR。CR率与诊断、性别或既往治疗无关。19例患者在CR状态下完成了计划的2年治疗。未观察到血栓栓塞或出血并发症。大多数PV患者的放血需求减少。14例最初PRV-1阳性的患者中有5例（36%）在PEG-IFN治疗下PRV-1表达恢复正常。副作用是23例患者中16例治疗失败的原因。然而，19例患者中只有8例在2年时报告有任何副作用。QLQ-C30显示在6个月时QoL的几个方面有临床显著损害；然而，在2年时，QoL测量值与基线无差异。
PEG-IFN有效降低了42例患者中29例的血小板计数，但只有19例患者在2年时维持CR。在一部分患者中观察到PRV-1阳性的逆转，提示PEG-IFN可能对恶性克隆有作用。对于能耐受其初始副作用的患者，PEG-IFN是一种有价值的治疗选择。
