Mori Yasuo
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science.
Rinsho Ketsueki. 2019;60(8):953-959. doi: 10.11406/rinketsu.60.953.
Graft-versus-host-disease (GvHD) is a major complication and leading cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Corticosteroids remain the standard initial therapy for GvHD; however, patients frequently become steroid-refractory (SR) or remain steroid dependent. Cytokine inhibition appears to be a potential option; however, blockade of any single cytokine may not be sufficient probably because of the redundant effects of multiple cytokines. The Jak1/2 inhibitor ruxolitinib can simultaneously inhibit the signaling pathway of multiple cytokines with relevance for GvHD, such as interferon (IFN-γ), IL-2, and IL-6. A recent retrospective survey reported that ruxolitinib produced a high response rate for SR-GvHD, leading to better survival odds. A prompt and sustained ruxolitinib response contributes to the steroid-sparing effect; however, accumulating evidence showed that ruxolitinib exerts substantial myelosuppression and immunosuppressive activity in patients with myelofibrosis (MF). Additionally, serious adverse events following discontinuation of ruxolitinib treatment, characterized by acute relapse of the disease and/or GvHD, have been recognized. Herein we discuss the advantages and disadvantages of ruxolitinib as treatment for GvHD in patients with MF.
移植物抗宿主病(GvHD)是异基因造血干细胞移植后的主要并发症和非复发死亡率的主要原因。皮质类固醇仍然是GvHD的标准初始治疗方法;然而,患者经常会出现类固醇难治性(SR)或仍然依赖类固醇。细胞因子抑制似乎是一种潜在的选择;然而,阻断任何单一细胞因子可能都不够,这可能是因为多种细胞因子具有冗余效应。Jak1/2抑制剂芦可替尼可以同时抑制与GvHD相关的多种细胞因子的信号通路,如干扰素(IFN-γ)、IL-2和IL-6。最近的一项回顾性调查报道,芦可替尼对SR-GvHD产生了高反应率,从而提高了生存几率。芦可替尼迅速且持续的反应有助于产生类固醇节省效应;然而,越来越多的证据表明,芦可替尼在骨髓纤维化(MF)患者中具有显著的骨髓抑制和免疫抑制活性。此外,芦可替尼治疗停药后出现的严重不良事件,其特征为疾病和/或GvHD的急性复发,已得到确认。在此,我们讨论芦可替尼作为MF患者GvHD治疗方法的优缺点。