Department of Pharmacy, City of Hope, Duarte, CA, USA.
Department of Medicine, Blood and Marrow Transplant Hematology, Keck Medicine of University of Southern California, Los Angeles, CA, USA.
Transplant Cell Ther. 2024 Nov;30(11):1091.e1-1091.e8. doi: 10.1016/j.jtct.2024.08.013. Epub 2024 Aug 24.
Myelofibrosis (MF) is a myeloproliferative neoplasm with a relapse rate of 10% to 30% after allogeneic transplantation (alloHCT). Current recommendations to treat relapse include withdrawal of immunosuppression, donor lymphocyte infusion, and potentially a second alloHCT. Hypomethylating agents (HMAs) have shown efficacy as salvage therapy by inducing an immune response and improving donor chimerism for myeloid neoplasm post-HCT. Data is limited on use of HMAs for MF post-alloHCT relapse. To determine the benefit of using HMAs for MF patients relapsing after alloHCT, we retrospectively analyzed 12 patients with MF post-alloHCT relapse who received HMA to determine response via restoration of donor chimerism and clearance of molecular mutation. The median age was 61 years (range 41-72) with 92% classified as intermediate-2/high-risk by the Dynamic International Prognostic Scoring System (DIPSS) and 83% as high/very high risk by the MIPSS70+ (Molecular International Prognostic Scoring System). The median time to relapse post-alloHCT was 282.5 days (range 96-2388) with median donor chimerism 57.82% (range 2.48-84.0) prior to starting an HMA. After two cycles of HMA, 58% experienced restoration of donor chimerism. Molecular clearance of pre-HCT driver mutations occurred in 50% of patients at the most recent follow-up. New chronic graft-vs.-host disease (cGVHD) occurred in 50% of patients, with most being mild to moderate that resolved after treatment. HMA was safe and effective in a high-risk population after post-alloHCT relapse and is an option for patients in the future.
骨髓纤维化（MF）是一种骨髓增生性肿瘤，异体造血干细胞移植（alloHCT）后复发率为 10%至 30%。目前治疗复发的建议包括撤回免疫抑制、供者淋巴细胞输注，以及潜在的第二次 alloHCT。低甲基化剂（HMAs）通过诱导免疫反应和改善 alloHCT 后髓性肿瘤供者嵌合率，已显示出作为挽救治疗的疗效。关于 alloHCT 后复发 MF 使用 HMAs 的数据有限。为了确定 HMAs 在 alloHCT 后复发 MF 患者中的应用获益，我们回顾性分析了 12 例接受 HMAs 治疗的 alloHCT 后复发 MF 患者，通过恢复供者嵌合率和清除分子突变来确定其反应。中位年龄为 61 岁（范围 41-72），92%根据动态国际预后评分系统（DIPSS）分类为中-2/高危，83%根据 MIPSS70+（分子国际预后评分系统）分类为高危/极高危。alloHCT 后复发中位时间为 282.5 天（范围 96-2388），在开始 HMA 治疗前供者嵌合率中位数为 57.82%（范围 2.48-84.0）。在接受两个周期的 HMA 治疗后，58%的患者恢复了供者嵌合率。在最近的随访中，50%的患者出现了预先存在的驱动突变的分子清除。50%的患者出现新的慢性移植物抗宿主病（cGVHD），大多数为轻度至中度，经治疗后缓解。在 alloHCT 后复发的高危人群中，HMA 安全且有效，是未来患者的一种选择。
