Fuji Shigeo
Department of Hematology, Osaka International Cancer Institute.
Rinsho Ketsueki. 2018;59(4):426-431. doi: 10.11406/rinketsu.59.426.
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell lymphoma caused by the human T-cell lymphotropic virus type I. Patients with aggressive ATL show dismal prognoses, even with intensive dose-dense chemotherapy. Such patients often show chemo-refractoriness. Mogamulizumab (Moga) is a potent treatment option for patients with relapsed or refractory ATL. However, use of Moga before allo-HSCT could theoretically increase the risk of post-transplant complications like graft-versus-host disease (GVHD) as Moga depletes regulatory T-cells (Tregs). We retrospectively assessed the impact of Moga on post-transplant outcomes using data from a nationwide survey. Pre-transplant administration of Moga was associated with an increased risk of grade 3 to 4 acute GVHD and refractoriness to systemic corticosteroid for acute GVHD. The one-year cumulative incidence of non-relapse mortality was significantly higher in patients who were treated with Moga pre-transplant compared with those who were not (43.7% vs. 25.1%, P<0.01). The probability of one-year overall survival was also significantly lower in patients with pre-transplant Moga use compared to those without (32.3% vs. 49.4%, P<0.01). In summary, pre-transplant Moga was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans.
成人T细胞白血病/淋巴瘤(ATL)是一种由I型人类嗜T细胞病毒引起的外周T细胞淋巴瘤。侵袭性ATL患者的预后不佳,即使采用强化剂量密集化疗也是如此。这类患者常表现出化疗难治性。莫加莫单抗(Moga)是复发或难治性ATL患者的一种有效治疗选择。然而,理论上在异基因造血干细胞移植(allo-HSCT)前使用Moga可能会增加移植后并发症的风险,如移植物抗宿主病(GVHD),因为Moga会消耗调节性T细胞(Tregs)。我们使用全国性调查的数据回顾性评估了Moga对移植后结局的影响。移植前使用Moga与3至4级急性GVHD风险增加以及对急性GVHD全身皮质类固醇难治性相关。移植前接受Moga治疗的患者与未接受治疗的患者相比,非复发死亡率的一年累积发生率显著更高(43.7%对25.1%,P<0.01)。移植前使用Moga的患者与未使用的患者相比,一年总生存率的概率也显著更低(32.3%对49.4%,P<0.01)。总之,移植前使用Moga与GVHD相关死亡率风险增加显著相关,这支持了人类allo-HSCT后表达CCR4的Tregs的相关性。