Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.
Cancer Center, University of Illinois, Chicago, IL, USA.
Bone Marrow Transplant. 2019 Jul;54(7):980-986. doi: 10.1038/s41409-018-0361-8. Epub 2018 Oct 19.
Myeloablative conditioning regimens with significant extramedullary toxicity result in high rates of renal dysfunction including acute kidney injury (AKI). Here we examine the incidence and impact of a reduced creatinine clearance (below 60 ml/min) before day 90 (early renal dysfunction, ERD) in patients receiving the reduced toxicity fludarabine/i.v. busulfan (FluBu4) regimen prior to allogeneic transplant. Of 91 patients receiving FluBu4, 62 (68%) developed ERD. ERD resulted in worse overall survival (OS, 2.2 years versus median not reached, p = 0.04) and progression-free survival (PFS, 1.6 years versus median not reached, p = 0.02). This was due to a higher relapse rate (34% versus 14%, p = 0.03) in the ERD group. In time-dependent Cox proportional hazards models adjusted for age, ERD was associated with worse OS (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.06-4.21, p = 0.043) and PFS (HR 2.52, 95% CI 1.17-4.28, p = 0.030). Patients with ERD surviving 1 year had an increased risk of chronic kidney disease (CKD, OR 10; 95% CI 1.4-112.6, p = 0.0181), which was associated with worse survival (3.2 years versus median not reached, p = 0.002). ERD after FluBu4 is therefore a poor prognostic sign resulting in increased relapse, worse OS, and high risk of CKD at 1 year.
在接受异体移植前接受低毒性氟达拉滨/静脉注射白消安（FluBu4）方案的患者中，我们检查了第 90 天（早期肾功能障碍，ERD）前肌酐清除率（低于 60ml/min）降低的发生率和影响。在接受 FluBu4 的 91 名患者中，有 62 名（68%）发生 ERD。ERD 导致总生存率（OS，2.2 年与未达到中位数，p=0.04）和无进展生存率（PFS，1.6 年与未达到中位数，p=0.02）更差。这是由于 ERD 组的复发率更高（34%比 14%，p=0.03）。在调整年龄的时间依赖性 Cox 比例风险模型中，ERD 与更差的 OS（风险比[HR]2.67，95%置信区间[CI]1.06-4.21，p=0.043）和 PFS（HR 2.52，95%CI 1.17-4.28，p=0.030）相关。ERD 存活 1 年的患者发生慢性肾脏病（CKD）的风险增加（OR 10；95%CI 1.4-112.6，p=0.0181），这与更差的生存相关（3.2 年与未达到中位数，p=0.002）。因此，FluBu4 后 ERD 是预后不良的标志，导致复发增加、OS 更差和 1 年内 CKD 风险增加。
