Leukemic transformation in myeloproliferative neoplasms (MPN), also referred to as “blast-phase MPN”, is the most feared disease complication, with incidence estimates of 1–4% for essential thrombocythemia, 3–7% for polycythemia vera, and 9–13% for primary myelofibrosis. Diagnosis of MPN-BP requires the presence of ≥20% circulating or bone marrow blasts; a lower level of excess blasts (10–19%) constitutes “accelerated phase” disease (MPN-AP). Neither “intensive” nor “less intensive” chemotherapy, by itself, secures long-term survival in MPN-BP. Large-scale retrospective series have consistently shown a dismal prognosis in MPN-BP, with 1- and 3-year survival estimates of <20% and <5%, respectively. Allogeneic hematopoietic stem cell transplant (AHSCT) offers the possibility of a >30% 3-year survival rate and should be pursued, ideally, while the patient is still in chronic phase disease. The value of pre-transplant bridging chemotherapy is uncertain in MPN-AP while it is advised in MPN-BP; in this regard, we currently favor combination chemotherapy with venetoclax (Ven) and hypomethylating agent (HMA); response is more likely in the absence of complex/monosomal karyotype and presence of TET2 mutation. Furthermore, in the presence of an IDH mutation, the use of IDH inhibitors, either alone or in combination with Ven-HMA, can be considered. Pre-transplant clearance of excess blasts is desired but not mandated; in this regard, additional salvage chemotherapy is more likely to compromise transplant eligibility rather than improve post-transplant survival. Controlled studies are needed to determine the optimal pre- and post-transplant measures that target transplant-associated morbidity and post-transplant relapse.
骨髓增殖性肿瘤（MPN）的白血病转化，亦称“急变期MPN”，是最令人担忧的疾病并发症。其发生率估算为：原发性血小板增多症1-4%，真性红细胞增多症3-7%，原发性骨髓纤维化9-13%。MPN急变期的诊断需满足外周血或骨髓原始细胞≥20%；原始细胞轻度增多（10-19%）则构成“加速期”疾病（MPN-AP）。无论是“强化”还是“低强度”化疗，均无法单独确保MPN急变期的长期生存。大规模回顾性研究一致显示MPN急变期预后极差，1年和3年生存率分别低于20%和5%。异基因造血干细胞移植可实现超过30%的3年生存率，应作为治疗目标，理想情况下应在患者仍处于慢性期时进行。移植前桥接化疗在MPN加速期中的价值尚不明确，而在MPN急变期中则建议实施；对此，目前我们倾向于维奈克拉联合去甲基化药物的化疗方案；若无复杂/单染色体核型且存在TET2突变，治疗反应更佳。此外，若存在IDH突变，可考虑使用IDH抑制剂，单药或与维奈克拉-去甲基化药物联合方案均可。移植前清除多余原始细胞虽理想但非强制要求；在这方面，额外的挽救化疗更可能损害移植资格而非改善移植后生存。需要通过对照研究来确定针对移植相关并发症及移植后复发的最佳移植前后干预措施。
Blast phase myeloproliferative neoplasm: contemporary review and 2024 treatment algorithm
肿瘤(癌症)患者之家