Nguyen Tina, Markary Tanya, Tsai Ni-Chun, Tiemann Katrin, Mokhtari Sally, Samara Yazeed, Pourhassan Hoda, Blackmon Amanda, Arslan Shukaib, Otoukesh Salman, Agarwal Vaibhav, Amanam Idoroenyi, Ball Brian, Koller Paul, Aribi Ahmed, Salhotra Amandeep, Sandhu Karamjeet, Pullarkat Vinod, Becker Pamela, Aldoss Ibrahim, Ali Haris, Stewart Forrest, Smith Eileen, Stein Anthony, Marcucci Guido, Forman Stephen J, Artz Andrew, Nakamura Ryotaro, Al Malki Monzr M
Department of Pharmacy, City of Hope National Medical Center, Duarte, California.
Department of Computational and Quantitative Medicine, Division of Biostatistics, City of Hope National Medical Center, Duarte, California.
Transplant Cell Ther. 2025 Jul 3. doi: 10.1016/j.jtct.2025.07.001.
Renal impairment is associated with poor outcomes following allogeneic hematopoietic cell transplantation (HCT). Although melphalan-based reduced-intensity conditioning (RIC) is demonstrated to be safe and feasible in older HCT patients, the impact of renal impairment on outcomes and toxicities following melphalan-based RIC is not well described. To evaluate how pretransplant renal function influences toxicity and survival after fludarabine/melphalan (FM) RIC and to compare measured 24-h urine creatinine clearance (UCrCl) with calculated creatinine-based renal function estimates as prognostic markers. Herein, we describe long-term outcomes of 561 HCT patients aged 55 to 74 years who received FM conditioning and tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis prior to matched donor HCT, between July 2009 and December 2019. Patients were divided based on pre-HCT UCrCl: creatinine clearance (CrCl) <90 mL/min (UCrCl 2 to 3, n = 184) and CrCl ≥90 mL/min (UCrCl 0 to 1, n = 377). CrCl for all patients was also calculated by the Cockcroft-Gault and the 2021 Chronic Kidney Disease Epidemiology Collaboration equations for comparison. UCrCl 2 to 3 correlated with higher 4-year non-relapse mortality (31% versus 19%, P < .01) and lower 4-year overall survival (55% versus 62%, P = .03) without differences in relapse rates. Neither CrCl calculation method correlated with any survival endpoint. UCrCl 2 to 3 was associated with higher severity and incidence of melphalan-related adverse events. Lower UCrCl was associated with less melphalan-induced severe GVHD- and gastrointestinal toxicity-free survival (MGTFS), a composite endpoint for severe melphalan-related morbidity and mortality at day +30 post-HCT and an early correlate of long-term survival outcomes (UCrCl 2 to 3: 18% versus UCrCl 0 to 1: 31%, P < .01). Patients with poor baseline UCrCl receiving melphalan-based RIC are at risk for significant conditioning-related toxicity and GVHD and, consequently, increased mortality. MGTFS quantified the early effect of FM RIC-related toxicities on post-HCT survival in this renally impaired HCT population.
肾损伤与异基因造血细胞移植（HCT）后的不良预后相关。尽管基于美法仑的减低强度预处理（RIC）已被证明在老年HCT患者中是安全可行的，但肾损伤对基于美法仑的RIC后预后和毒性的影响尚未得到充分描述。为了评估移植前肾功能如何影响氟达拉滨/美法仑（FM）RIC后的毒性和生存，并比较实测的24小时尿肌酐清除率（UCrCl）与基于肌酐计算的肾功能估计值作为预后标志物。在此，我们描述了2009年7月至2019年12月期间561例年龄在55至74岁之间的HCT患者的长期预后，这些患者接受了FM预处理，并在匹配供体HCT前接受他克莫司/西罗莫司预防移植物抗宿主病（GVHD）。根据移植前UCrCl将患者分为两组：肌酐清除率（CrCl）<90 mL/分钟（UCrCl 2至3，n = 184）和CrCl≥90 mL/分钟（UCrCl 0至1，n = 377）。所有患者的CrCl也通过Cockcroft-Gault和2021年慢性肾脏病流行病学协作组方程进行计算以作比较。UCrCl 2至3与较高的4年非复发死亡率相关（31%对19%，P <.01），4年总生存率较低（55%对62%，P =.03），复发率无差异。两种CrCl计算方法均与任何生存终点无关。UCrCl 2至3与美法仑相关不良事件的更高严重程度和发生率相关。较低的UCrCl与较少的美法仑诱导的严重无移植物抗宿主病和无胃肠道毒性生存期（MGTFS）相关，MGTFS是HCT后第30天严重美法仑相关发病率和死亡率的综合终点，也是长期生存结果的早期相关指标（UCrCl 2至3：18%对UCrCl 0至1：31%，P <.01）。接受基于美法仑的RIC且基线UCrCl较差的患者有发生显著预处理相关毒性和GVHD的风险，因此死亡率增加。MGTFS量化了FM RIC相关毒性对该肾损伤HCT人群HCT后生存的早期影响。
