Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Medicine, Division of Hematology & Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts.
Transplant Cell Ther. 2023 Jul;29(7):455.e1-455.e9. doi: 10.1016/j.jtct.2023.03.029. Epub 2023 Apr 2.
Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative therapy for patients with hematologic malignancies but is associated with acute kidney injury (AKI). To date, few studies have examined risk factors for AKI at engraftment, or the relationship between AKI and clinical outcomes. This study examined the incidence and risk factors for periengraftment AKI, as well as the association between AKI and overall survival (OS) and nonrelapse mortality (NRM). We conducted a retrospective analysis of adult patients undergoing reduced-intensity conditioning (RIC) allogeneic HCT at the Dana-Farber Cancer Institute between 2012 and 2019. Periengraftment (day 0 to day 30) AKI incidence and severity were defined using modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Factors associated with periengraftment AKI risk were examined using Cox regression analysis. The impact of periengraftment AKI on OS and NRM (defined as death without recurrent disease after HCT), was evaluated using Cox regression and the Fine and Gray competing risks model, respectively. Kidney recovery, defined as a return of serum creatinine (SCr) to within 25% of baseline or liberation from kidney replacement therapy (KRT), was examined at day 90 post-HCT. Periengraftment AKI occurred in 330 of 987 patients (33.4%) at a median of 13 days (interquartile range, 4 to 30 days) post-transplantation. Factors associated with a higher multivariable-adjusted risk of AKI were supratherapeutic rapamycin (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.20 to 2.03; P < .001), fludarabine/melphalan conditioning (HR, 1.35, 95% CI, 1.01 to 1.81; P = .05, compared to fludarabine/busulfan and fludarabine, cyclophosphamide, and total body irradiation), HCT Comorbidity Index ≥4 (HR, 1.43; 95% CI, 1.14 to 1.79; P = .002), albumin <3.4 g/dL (HR, 2.04; 95% CI, 1.33 to 3.12; P = .001), hemoglobin ≤12 (HR, 1.96; 95% CI, 1.38 to 2.78; P < .001), supratherapeutic tacrolimus (HR, 1.45; 95% CI, 1.07 to 1.95; P = .02), and baseline SCr >1.1 mg/dL (HR, 1.87; 95% CI, 1.48 to 2.35; P < .001). Periengraftment AKI was associated with worse OS (HR, 1.40; 95% CI, 1.16 to 1.71; P < .001) and NRM (subdistribution HR, 2.10; 95% CI, 1.52 to 2.89; P < .001). Kidney recovery occurred in 18%, 15%, and 30% of patients with stage 1, stage 2, and stage 3 AKI without KRT, respectively, and 4 of 16 patients (25%) were liberated from KRT. Periengraftment AKI is common among RIC allogeneic HCT recipients. We identified several important risk factors for periengraftment AKI. Its association with worse OS and NRM underscores the importance of timely recognition and management.
异基因造血干细胞移植(HCT)是治疗血液系统恶性肿瘤的潜在治愈性疗法,但与急性肾损伤(AKI)相关。迄今为止,很少有研究检查移植期 AKI 的发病风险因素,或 AKI 与临床结果之间的关系。本研究检查了移植期 AKI 的发生率和风险因素,以及 AKI 与总生存(OS)和非复发死亡率(NRM)之间的关系。我们对 2012 年至 2019 年在达纳-法伯癌症研究所接受低强度预处理(RIC)异基因 HCT 的成年患者进行了回顾性分析。使用改良的 KDIGO(肾脏疾病:改善全球结局)标准定义移植期(第 0 天至第 30 天)AKI 的发生率和严重程度。使用 Cox 回归分析检查与移植期 AKI 风险相关的因素。使用 Cox 回归和 Fine 和 Gray 竞争风险模型分别评估移植期 AKI 对 OS 和 NRM(定义为 HCT 后无疾病复发的死亡)的影响。在 HCT 后第 90 天检查肾脏恢复情况,定义为血清肌酐(SCr)恢复到基线的 25%以内或脱离肾脏替代治疗(KRT)。在 987 例患者中,330 例(33.4%)在移植后中位 13 天(四分位距 4 至 30 天)发生移植期 AKI。多变量调整后的 AKI 发病风险较高的相关因素包括超治疗性雷帕霉素(危险比[HR],1.56;95%置信区间[CI],1.20 至 2.03;P <.001)、氟达拉滨/马法兰预处理(HR,1.35,95%CI,1.01 至 1.81;与氟达拉滨/白消安和氟达拉滨、环磷酰胺和全身照射相比,P =.05)、HCT 合并症指数≥4(HR,1.43;95%CI,1.14 至 1.79;P =.002)、白蛋白<3.4 g/dL(HR,2.04;95%CI,1.33 至 3.12;P =.001)、血红蛋白≤12(HR,1.96;95%CI,1.38 至 2.78;P <.001)、超治疗性他克莫司(HR,1.45;95%CI,1.07 至 1.95;P =.02)和基线 SCr>1.1 mg/dL(HR,1.87;95%CI,1.48 至 2.35;P <.001)。移植期 AKI 与较差的 OS(HR,1.40;95%CI,1.16 至 1.71;P <.001)和 NRM(亚分布 HR,2.10;95%CI,1.52 至 2.89;P <.001)相关。在没有 KRT 的情况下,分别有 18%、15%和 30%的 1 期、2 期和 3 期 AKI 患者出现肾脏恢复,16 例患者中有 4 例(25%)脱离 KRT。RIC 异基因 HCT 受者中移植期 AKI 很常见。我们确定了移植期 AKI 的几个重要风险因素。其与较差的 OS 和 NRM 相关,强调了及时识别和管理的重要性。