Chien Nicole, Varghese Chris, Green Taryn N, Chan George, Theakston Edward, Eaddy Nicola, Doocey Richard, Berkahn Leanne, Hawkins Timothy, Browett Peter J, Kalev-Zylinska Maggie L
Department of Haematology, Auckland City Hospital, Auckland, New Zealand.
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
Leuk Res. 2020 Jun;93:106358. doi: 10.1016/j.leukres.2020.106358. Epub 2020 Apr 24.
All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are effective induction therapy for acute promyelocytic leukaemia (APL). However, early thrombo-haemorrhagic complications and mortality remain high. We aimed to investigate how the timing of ATRA initiation and the inclusion of ATO influence patient outcomes. Clinical records were retrospectively reviewed for all patients treated for APL in a single, tertiary centre during 2000-2017. Among 70 patients with APL, 36 (51.4%) presented with thrombo-haemorrhagic complications, and four (5.8%) died within 30 days. The median time to ATRA initiation was 11.2 (range 0-104) h from the time of admission. Patients requiring more transfusions started on ATRA sooner (P = 0.04). Patients with adverse early events did not start ATRA later (P = 0.99). Nevertheless, patients that required additional tests for diagnosis (PML immunofluorescence or molecular) started on ATRA later (28.5 versus 5.3 h; P < 0.0001), and had more thrombo-haemorrhagic complications (P = 0.04). Long-term survival was actually better in patients who started ATRA later (P = 0.03), which is likely explained by higher proportion of low risk patients in this group. Patients treated with ATO (n = 23) maintained higher fibrinogen levels and required less transfusions during induction (P < 0.05), with no disease-related deaths in this group over a median follow-up time of 37.8 months (interquartile range 44.9 months). In summary, fast ATRA initiation reduces early but not late adverse events in APL patients, and the inclusion of ATO helps further improve both early and late outcomes in APL.
全反式维甲酸（ATRA）和三氧化二砷（ATO）是急性早幼粒细胞白血病（APL）有效的诱导治疗药物。然而，早期血栓出血并发症和死亡率仍然很高。我们旨在研究开始使用ATRA的时机以及加入ATO如何影响患者的预后。对2000年至2017年期间在一家三级中心接受APL治疗的所有患者的临床记录进行了回顾性分析。在70例APL患者中，36例（51.4%）出现血栓出血并发症，4例（5.8%）在30天内死亡。从入院到开始使用ATRA的中位时间为11.2小时（范围0 - 104小时）。需要更多输血的患者开始使用ATRA的时间更早（P = 0.04）。有早期不良事件的患者开始使用ATRA的时间并不晚（P = 0.99）。然而，需要额外诊断检查（PML免疫荧光或分子检测）的患者开始使用ATRA的时间较晚（28.5小时对5.3小时；P < 0.0001），并且有更多的血栓出血并发症（P = 0.04）。开始使用ATRA较晚的患者长期生存率实际上更好（P = 0.03），这可能是因为该组中低风险患者的比例更高。接受ATO治疗的患者（n = 23）在诱导期间纤维蛋白原水平维持较高，输血需求较少（P < 0.05），在中位随访时间37.8个月（四分位间距44.9个月）内该组无疾病相关死亡。总之，快速开始使用ATRA可减少APL患者的早期但非晚期不良事件，加入ATO有助于进一步改善APL患者的早期和晚期预后。
