Division of Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, Minnesota.
Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama.
Biol Blood Marrow Transplant. 2019 Dec;25(12):2454-2460. doi: 10.1016/j.bbmt.2019.07.030. Epub 2019 Aug 5.
Frailty is a state characterized by diminished physiologic reserve and increased vulnerability to stress and adversely affects outcomes in older patients. We aimed to determine the relationship between pre-hematopoietic cell transplant (HCT) frailty and grades 3 to 4 nonhematologic toxicities (Common Terminology Criteria for Adverse Events, version 5.0) and mortality in HCT recipients within 1 year after HCT and also examined whether age at HCT moderated that association. In a prospective longitudinal study of 117 patients aged ≥ 40 years undergoing HCT, we performed formal pre-HCT geriatric assessments. Frailty was assessed using Fried's criteria. Post-HCT toxicities were abstracted through medical record reviews. The prevalence of pre-HCT frailty was 21% and was not different in younger (40 to 59 years) versus older (≥60 years) HCT recipients. Overall, frail recipients (versus nonfrail) had a higher cumulative incidence of any grades 3 to 4 nonhematologic toxicity (86% [95% confidence interval {CI}, 62% to 100%] versus 70% [95% CI, 57% to 83%), P = .03) and more organ-specific grades 3 to 4 toxicities, such as non-neutropenic infections (38% [95% CI, 17% to 59%] versus 13% [95% CI, 6% to 20%], P < .01), nervous system disorders (19% [95% CI, 3% to 35%] versus 4% [95% CI, 0 to 8%], P = .02), and pneumonia (38% [95% CI, 17% to 59%] versus 10% [95% CI, 4% to 17%], P < .01). Frail recipients were 1.9-fold (95% CI, 1.1 to 3.4) more likely to develop any grades 3 to 4 toxicities (P = .03), 4-fold more likely to suffer non-neutropenic infections (95% CI, 1.4 to 11) and pneumonia (95% CI, 1.4 to 12; both P = .01), and 8.6-fold (95% CI, 1.6 to 45.3) more likely to suffer nervous system disorders (P = .01). Frail allogeneic HCT recipients also had a 3.1 times (95% CI, .9 to 9.7; P = .06) higher risk of overall mortality as compared with nonfrail allogeneic HCT recipients. The higher toxicity and mortality observed in frail allogeneic recipients needs to be monitored with high attention. Studies focusing on interventions to reduce frailty and manage morbidities are needed.
衰弱是一种以生理储备减少和对压力的易感性增加为特征的状态，会影响老年患者的结局。我们旨在确定造血细胞移植（HCT）前衰弱与 HCT 后 1 年内 3 至 4 级非血液学毒性（不良事件常用术语标准，版本 5.0）和死亡率之间的关系，并研究年龄是否调节了这种关联。在一项对 117 名年龄≥40 岁接受 HCT 的患者进行的前瞻性纵向研究中，我们进行了正式的 HCT 前老年评估。使用 Fried 的标准评估衰弱。通过病历回顾提取 post-HCT 毒性。HCT 前衰弱的患病率为 21%，在年龄较小（40 至 59 岁）和年龄较大（≥60 岁）的 HCT 接受者中并无差异。总体而言，衰弱的接受者（与非衰弱者相比）任何 3 至 4 级非血液学毒性的累积发生率更高（86%[95%置信区间（CI），62%至 100%]与 70%[95%CI，57%至 83%]，P=0.03），并且更多器官特异性的 3 至 4 级毒性，如非中性粒细胞减少性感染（38%[95%CI，17%至 59%]与 13%[95%CI，6%至 20%]，P<.01）、神经系统疾病（19%[95%CI，3%至 35%]与 4%[95%CI，0 至 8%]，P=0.02）和肺炎（38%[95%CI，17%至 59%]与 10%[95%CI，4%至 17%]，P<.01）。衰弱的接受者发生任何 3 至 4 级毒性的可能性高 1.9 倍（95%CI，1.1 至 3.4）（P=0.03），发生非中性粒细胞减少性感染和肺炎的可能性高 4 倍（95%CI，1.4 至 11 和 1.4 至 12；两者均 P=0.01），发生神经系统疾病的可能性高 8.6 倍（95%CI，1.6 至 45.3）（P=0.01）。与非衰弱的同种异体 HCT 接受者相比，衰弱的同种异体 HCT 接受者的总死亡率风险高 3.1 倍（95%CI，.9 至 9.7；P=0.06）。需要高度关注衰弱的同种异体接受者中观察到的更高毒性和死亡率。需要进行关注衰弱和管理合并症的干预措施研究。
