Background:Pre-fibrotic myelofibrosis (pre-PMF) is a rare subentity of myeloproliferative neoplasm (MPN) with limited overall survival and the potential for progression toward overt, symptomatic myelofibrosis or blastic transformation. To date, a consensus on the treatment of pre-PMF, especially in asymptomatic cases, has yet to be reached. Interferon therapy has been employed as an effective treatment for MPN for many decades, due to its immunomodulatory properties and disease-modifying effects.Methods:The objective of this monocentric study was to evaluate hematological, molecular, and clinical responses, as well as the overall outcome, to pegylated interferon (peginterferon) in pre-PMF cases harboring a JAK2 or CALR mutation.Results:In a cohort of 55 consecutive patients with a median follow-up period of 3.89 (1.63; 6.10) years, a high rate of complete hematological response (81%) was documented after 24 months. Deep molecular responses with a >50% reduction in allele burden were documented in 54.6% of the JAK2-mutated and 7.7% of CALR-mutated patients, respectively (p= 0.023). Concerning fibrosis, at least the stabilization of disease was achieved in 73% of evaluable patients. Furthermore, only one case of blastic transformation was observed, along with three cases of thromboembolic events in the JAK2-mutated cohort.Conclusions:The study confirms the substantial efficacy of interferon in pre-PMF patients with rapid hematological normalization in most patients. Molecular responses were striking, but largely confined to JAK2-mutated patients. To our knowledge, this is the largest retrospective cohort of strictly WHO-defined pre-PMF patients treated with interferon and observed for a reasonable duration of time.
背景：前纤维化骨髓纤维化（pre-PMF）是骨髓增殖性肿瘤（MPN）的一种罕见亚型，其总体生存期有限，并具有向明显症状性骨髓纤维化或急变转化的潜在风险。迄今为止，针对pre-PMF的治疗，尤其是无症状病例，尚未达成共识。干扰素疗法因其免疫调节特性和疾病修饰作用，数十年来一直被用作MPN的有效治疗手段。 方法：本单中心研究旨在评估携带JAK2或CALR突变的pre-PMF患者对聚乙二醇干扰素（peginterferon）的血液学、分子学及临床反应，以及总体结局。 结果：在连续入组的55例患者中，中位随访时间为3.89（1.63；6.10）年。治疗24个月后，观察到较高的完全血液学缓解率（81%）。在JAK2突变患者中，54.6%达到等位基因负荷降低>50%的深度分子学缓解，而CALR突变患者中该比例为7.7%（p=0.023）。在纤维化方面，73%的可评估患者至少实现了疾病稳定。此外，仅在JAK2突变队列中观察到1例急变转化事件和3例血栓栓塞事件。 结论：本研究证实了干扰素在pre-PMF患者中的显著疗效，大多数患者实现了快速的血液学正常化。分子学反应显著，但主要局限于JAK2突变患者。据我们所知，这是目前规模最大的、严格依据WHO标准定义的pre-PMF患者接受干扰素治疗并经过合理时长随访的回顾性队列研究。
肿瘤(癌症)患者之家