Adult T-cell leukemia-lymphoma (ATL) is an aggressive mature lymphoid proliferation associated with poor prognosis. Standard of care includes chemotherapy and/or the combination of zidovudine and interferon-alpha. However, most patients experience relapse less than 6 months after diagnosis. Allogeneic stem cell transplantation is the only curative treatment, but is only feasible in a minority of cases. We previously showed in a mouse model that Arsenic trioxide (As2O3) targets ATL leukemia initiating cells. As2O3 consolidation was given in 9 patients with ATL (lymphoma n = 4; acute n = 2; and indolent n = 3), who were in complete (n = 4) and partial (n = 3) remission, in stable (n = 1) and in progressive (n = 1) disease. Patients received up to 8 weeks of As2O3 at the dose of 0.15 mg/kg/day intravenously in combination with zidovudine and interferon-alpha. One patient in progression died rapidly. Of the remaining eight patients, three with indolent ATL subtype showed overall survivals of 48, 53 and 97 months, and duration of response to As2O3 of 22, 25 and 73 months. The other 5 patients with aggressive ATL subtype had median OS of 36 months and a median duration of response of 10 months. Side effects were mostly hematological and cutaneous (one grade 3) and reversible with dose reduction of AZT/IFN and/or As2O3 discontinuation. The virus integration analysis revealed the regression of the predominant malignant clone in one patient with a chronic subtype. These results suggest that consolidation with As2O3 could be an option for patients with ATL in response after induction therapy and who are not eligible for allogeneic stem cell transplantation.

中文翻译：

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三氧化二砷 (As2O3) 作为成人 T 细胞白血病/淋巴瘤的维持疗法

成人 T 细胞白血病淋巴瘤 (ATL) 是一种侵袭性的成熟淋巴样增殖，预后不良。护理标准包括化疗和/或齐多夫定和干扰素-α 的组合。然而，大多数患者在诊断后不到 6 个月就会复发。同种异体干细胞移植是唯一的治愈性治疗方法，但仅在少数情况下可行。我们之前在小鼠模型中表明，三氧化二砷 (As2O3) 靶向 ATL 白血病起始细胞。9 名 ATL 患者（淋巴瘤 n = 4；急性 n = 2；惰性 n = 3）接受了 As2O3 巩固治疗，这些患者完全 (n = 4) 和部分 (n = 3) 缓解，稳定 (n = 1) 和进展 (n = 1) 疾病。患者接受长达 8 周的 As2O3，剂量为 0。15 mg/kg/天与齐多夫定和干扰素-α 联合静脉内给药。一名进展中的患者迅速死亡。在其余 8 名患者中，3 名惰性 ATL 亚型患者的总生存期为 48、53 和 97 个月，对 As2O3 的反应持续时间为 22、25 和 73 个月。其他 5 名侵袭性 ATL 亚型患者的中位 OS 为 36 个月，中位反应持续时间为 10 个月。副作用主要是血液和皮肤（3 级），并且随着 AZT/IFN 的剂量减少和/或 As2O3 的停止而可逆。病毒整合分析揭示了一名慢性亚型患者的主要恶性克隆消退。