Service d'Hématologie Adultes, Institut Imagine, Hôpital Universitaire Necker Enfants Malades, APHP, Université de Paris, 149-161 rue de Sèvres, 75743, Paris Cedex 15, France.
Section of Virology, Wright-Fleming Institute, Imperial College, London, UK.
Retrovirology. 2020 Mar 21;17(1):5. doi: 10.1186/s12977-020-0513-y.
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 (AsO) targets ATL leukemia initiating cells.
AsO 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 AsO 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 AsO 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 AsO 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 AsO could be an option for patients with ATL in response after induction therapy and who are not eligible for allogeneic stem cell transplantation.
成人 T 细胞白血病/淋巴瘤（ATL）是一种与预后不良相关的侵袭性成熟淋巴细胞增生。标准治疗包括化疗和/或齐多夫定和干扰素-α联合治疗。然而，大多数患者在诊断后不到 6 个月就会复发。异基因造血干细胞移植是唯一的治愈性治疗方法，但仅适用于少数病例。我们之前在小鼠模型中表明，三氧化二砷（AsO）靶向 ATL 白血病起始细胞。
9 例 ATL 患者（淋巴瘤 n=4；急性 n=2；惰性 n=3）在完全缓解（n=4）和部分缓解（n=3）、稳定（n=1）和进展（n=1）疾病中接受了 AsO 巩固治疗。患者接受了长达 8 周的 0.15mg/kg/天的静脉注射 AsO 联合齐多夫定和干扰素-α治疗。1 例进展期患者迅速死亡。在其余 8 例患者中，3 例惰性 ATL 亚型患者的总生存率分别为 48、53 和 97 个月，AsO 反应持续时间分别为 22、25 和 73 个月。另外 5 例侵袭性 ATL 亚型患者的中位 OS 为 36 个月，中位反应时间为 10 个月。不良反应主要为血液学和皮肤学（1 级 3 级），并通过减少 AZT/IFN 的剂量和/或停止使用 AsO 而可逆。病毒整合分析显示，1 例慢性亚型患者的主要恶性克隆出现消退。
这些结果表明，在诱导治疗后有反应且不适合进行异基因造血干细胞移植的 ATL 患者，AsO 巩固治疗可能是一种选择。
