目的:关于淋巴瘤患者接受葡萄糖苷酶后甲氨蝶呤(MTX)恢复毒性MTX水平和急性肾损伤(AKI)的证据有限。
方法:这项回顾性研究纳入了2020年1月31日至2022年10月10日在梅奥诊所接受MTX治疗后接受葡萄糖苷酶治疗的淋巴瘤成人患者。描述性统计数据总结了患者特征和临床结果。
结果:在11例MTX后接受葡萄糖苷酶治疗的患者中,7人(64%)接受MTX再攻击。MTX再激发的适应症包括确诊的CNS疾病(n=6,86%)和血管内淋巴瘤(n=1,14%)。与未重新挑战的亚组相比,在接受需要葡糖苷酶拯救的MTX之前,复检患者治疗前血清肌酐中位数较低(Scr;0.7v1.2mg/dL),以前的MTX剂量没有AKI,n=0(0%)对n=2(50%)。在MTX剂量需要葡萄糖苷酶拯救期间,再次攻击组的Scr中位数较低(1.26v3.32mg/dL),AKIIII期发生率较低(n=1[14%]vn=3[75%]),并且没有一个被攻击的患者需要肾脏替代治疗(RRT;n=0[0%]vn=1[25%])。在葡萄糖苷酶给药后的第一次再攻击时,MTX剂量减少中位数为56%(范围,46%-75%),根据每个治疗方案时间表规定的最低使用剂量为1.5g/m2。两名(29%)患者经历了AKI(n=1个I期,n=1阶段II)MTX再激发后。零患者需要RRT,零需要再次施用葡糖脂酶。六名(86%)患者完成了所有推荐的MTX剂量。
结论:在服用大剂量MTX后需要葡萄糖苷酶才能达到毒性MTX水平的淋巴瘤患者中,以较低剂量恢复MTX治疗是安全的。与未选择用于MTX恢复的患者相比,选择用于MTX恢复的患者在先前周期期间经历了较少严重的AKI。
OBJECTIVE: Limited evidence exists regarding methotrexate (MTX) resumption after patients with lymphoma receive glucarpidase for toxic MTX levels and acute kidney injury (AKI).
METHODS: This retrospective review included adults with lymphoma treated with glucarpidase after MTX at Mayo Clinic between January 31, 2020, and October 10, 2022. Descriptive statistics summarize patient characteristics and clinical outcomes.
RESULTS: Of 11 patients treated with glucarpidase after MTX, seven (64%) were rechallenged with MTX. Indications for MTX rechallenge included confirmed CNS disease (n = 6, 86%) and intravascular lymphoma (n = 1, 14%). Compared with the nonrechallenged subgroup, before receiving MTX that required glucarpidase rescue, the rechallenged patients had lower median pretreatment serum creatinine (Scr; 0.7 v 1.2 mg/dL), and none had AKI with previous MTX doses, n = 0 (0%) versus n = 2 (50%). During the MTX dose requiring glucarpidase rescue, the rechallenged group had lower median peak Scr (1.26 v 3.32 mg/dL) and lower incidence of AKI stage III (n = 1 [14%] v n = 3 [75%]), and none of the rechallenged patients required renal replacement therapy (RRT; n = 0 [0%] v n = 1 [25%]). At the first rechallenge after glucarpidase administration, the median MTX dose reduction was 56% (range, 46%-75%), and the lowest used dose when prescribed according to each treatment protocol schedule was 1.5 g/m2. Two (29%) patients experienced AKI (n = 1 stage I, n = 1 stage II) after MTX rechallenge. Zero patients required RRT, and zero required another glucarpidase administration. Six (86%) patients completed all recommended MTX doses.
CONCLUSIONS: In selected adults with lymphoma who required glucarpidase for toxic MTX levels after administration of high-dose MTX, resumption of MTX therapy at lower doses is safe. Patients selected for MTX resumption had experienced less severe AKI during the previous cycle compared with those not selected for MTX resumption.