UOC di Ematologia Con Trapianto di Midollo Osseo AOU Policlinico G. Rodolico-San Marco, Via Santa Sofia 78, 95123, Catania, Italy.
Department of Oncology, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milano, Italy.
Cancer Chemother Pharmacol. 2022 Feb;89(2):267-270. doi: 10.1007/s00280-021-04356-5. Epub 2021 Sep 29.
Relapse at the central nervous system (CNS) in acute myeloid leukemia (AML) carries a dismal prognosis. Treatment options are limited to intrathecal therapy, high-dose cytarabine, high-dose methotrexate, and radiotherapy. Novel strategies are needed. Venetoclax has recently been approved by the FDA, in combination with hypomethylating agents or low-dose cytarabine, for elderly adults or patients ineligible for intensive chemotherapy affected by AML. However, little is known on its efficacy in patients with leptomeningeal involvement. Here, we present a case of a 52-year-old patient affected by AML relapsed at CNS after allogeneic bone marrow transplantation who was treated with venetoclax. We evaluated the concentration of the drug in cerebrospinal fluid (CSF) by HPLC MS/MS method on three different occasions to verify the penetration of the drug through the brain-blood barrier and we observed that the concentration in CSF was similar to the IC50 established in vitro.
急性髓系白血病(AML)中枢神经系统(CNS)复发预后不良。治疗选择仅限于鞘内治疗、高剂量阿糖胞苷、高剂量甲氨蝶呤和放疗。需要新的策略。Venetoclax 最近已被 FDA 批准与低剂量阿糖胞苷或去甲基化药物联合用于年龄较大或不适合强化化疗的 AML 患者。然而,对于脑膜受累患者的疗效知之甚少。在这里,我们报告了一例 52 岁 AML 患者,在异基因骨髓移植后 CNS 复发,接受 Venetoclax 治疗。我们通过 HPLC-MS/MS 方法在三个不同的时间点评估了药物在脑脊液(CSF)中的浓度,以验证药物穿透血脑屏障的能力,我们观察到 CSF 中的浓度与体外建立的 IC50 相似。