Farhadfar Nosha, Dias Ajoy, Wang Tao, Fretham Caitrin, Chhabra Saurabh, Murthy Hemant S, Broglie Larisa, D'Souza Anita, Gadalla Shahinaz M, Gale Robert Peter, Hashmi Shahrukh, Al-Homsi A Samer, Hildebrandt Gerhard C, Hematti Peiman, Rizzieri David, Chee Lynette, Lazarus Hillard M, Bredeson Christopher, Jaimes Edgar A, Beitinjaneh Amer, Bashey Asad, Prestidge Tim, Krem Maxwell M, Marks David I, Benoit Stefanie, Yared Jean A, Nishihori Taiga, Olsson Richard F, Freytes Cesar O, Stadtmauer Edward, Savani Bipin N, Sorror Mohamed L, Ganguly Siddhartha, Wingard John R, Pasquini Marcelo
Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, Florida.
Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Transplant Cell Ther. 2021 May;27(5):410-422. doi: 10.1016/j.jtct.2021.02.030. Epub 2021 Feb 26.
Renal dysfunction is a recognized risk factor for mortality after allogeneic hematopoietic cell transplantation (alloHCT), yet our understanding of the effect of different levels of renal dysfunction at time of transplantation on outcomes remains limited. This study explores the impact of different degrees of renal dysfunction on HCT outcomes and examines whether the utilization of incremental degrees of renal dysfunction based on estimated glomerular filtration rate (eGFR) improve the predictability of the hematopoietic cell transplantation comorbidity index (HCT-CI). The study population included 2 cohorts: cohort 1, comprising patients age ≥40 years who underwent alloHCT for treatment of hematologic malignancies between 2008 and 2016 (n = 13,505; cohort selected given a very low incidence of renal dysfunction in individuals age <40 years), and cohort 2, comprising patients on dialysis at the time of HCT (n = 46). eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. The patients in cohort 1 were assigned into 4 categories-eGFR ≥90 mL/min (n = 7062), eGFR 60 to 89 mL/min (n = 5264), eGFR 45 to 59 mL/min (n = 897), and eGFR <45 mL/min (n=282)-to assess the impact of degree of renal dysfunction on transplantation outcomes. Transplantation outcomes in patients on dialysis at the time of alloHCT were analyzed separately. eGFR <60 mL/min was associated with an increased risk for nonrelapse mortality (NRM) and requirement for dialysis post-HCT. Compared with the eGFR ≥90 group, the hazard ratio (HR) for NRM was 1.46 (P = .0001) for the eGFR 45 to 59 mL/min group and 1.74 (P = .004) for the eGFR <45 mL/min group. Compared with the eGFR ≥90 mL/min group, the eGFR 45 to 59 mL/min group (HR, 2.45; P < .0001) and the eGFR <45 mL/min group (HR, 3.09; P < .0001) had a higher risk of renal failure necessitating dialysis after alloHCT. In addition, eGFR <45 mL/min was associated with an increased overall mortality (HR, 1.63; P < .0001). An eGFR-based revised HCT-CI was also developed and shown to be predictive of overall survival (OS) and NRM, with predictive performance similar to the original HCT-CI. Among 46 patients on dialysis at alloHCT, the 1-year probability of OS was 20%, and that of NRM was 67%. The degree of pretransplantation renal dysfunction is an independent predictor of OS, NRM, and probability of needing dialysis after alloHCT. An eGFR-based HCT-CI is a validated index for predicting outcomes in adults with hematologic malignancies undergoing alloHCT. The outcomes of alloHCT recipients on dialysis are dismal; therefore, one should strongly weigh the significant risks of being on hemodialysis as a factor in determining alloHCT candidacy.
肾功能不全是异基因造血细胞移植(alloHCT)后公认的死亡风险因素,但我们对移植时不同程度的肾功能不全对预后的影响仍了解有限。本研究探讨了不同程度的肾功能不全对造血细胞移植(HCT)预后的影响,并检验了基于估计肾小球滤过率(eGFR)的肾功能不全分级是否能提高造血细胞移植合并症指数(HCT-CI)的预测能力。研究人群包括2个队列:队列1由2008年至2016年间接受alloHCT治疗血液系统恶性肿瘤的年龄≥40岁的患者组成(n = 13,505;选择该队列是因为年龄<40岁的个体肾功能不全发生率极低),队列2由HCT时正在透析的患者组成(n = 46)。使用慢性肾脏病流行病学合作组(CKD-EPI)方法测量eGFR。队列1中的患者被分为4类——eGFR≥90 mL/分钟(n = 7062)、eGFR 60至89 mL/分钟(n = 5264)、eGFR 45至59 mL/分钟(n = 897)和eGFR<45 mL/分钟(n = 282)——以评估肾功能不全程度对移植预后的影响。对alloHCT时正在透析的患者的移植预后进行单独分析。eGFR<60 mL/分钟与非复发死亡率(NRM)增加及HCT后透析需求增加相关。与eGFR≥90组相比,eGFR 45至59 mL/分钟组NRM的风险比(HR)为1.46(P = .0001),eGFR<45 mL/分钟组为1.74(P = .004)。与eGFR≥90 mL/分钟组相比,eGFR 45至59 mL/分钟组(HR,2.45;P < .0001)和eGFR<45 mL/分钟组(HR,3.09;P < .0001)alloHCT后需要透析的肾衰竭风险更高。此外,eGFR<45 mL/分钟与总死亡率增加相关(HR,1.63;P < .0001)。还开发了基于eGFR的修订HCT-CI,结果显示其对总生存(OS)和NRM具有预测性,预测性能与原始HCT-CI相似。在alloHCT时正在透析的46例患者中,OS的1年概率为20%,NRM的1年概率为67%。移植前肾功能不全的程度是OS、NRM及alloHCT后需要透析概率的独立预测因素。基于eGFR的HCT-CI是预测接受alloHCT的血液系统恶性肿瘤成年患者预后的有效指标。alloHCT时正在透析的受者预后不佳;因此,在确定alloHCT候选资格时,应充分权衡血液透析的重大风险因素。