Department of Medicine, Blood and Marrow Transplant Program, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota.
Biostatistics and Informatics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Transplant Cell Ther. 2024 Sep;30(9):919.e1-919.e9. doi: 10.1016/j.jtct.2024.05.026. Epub 2024 Jun 3.
Frailty is a phenotype of decreased physiologic reserve associated with increased risk of toxicities and nonrelapse mortality (NRM) in hematopoietic cell transplant (HCT) recipients. The incidence, predictors, and adverse effects of pre-HCT frailty are not well known. We evaluated the association of pre-HCT frailty, defined using Fried's criteria, with age and baseline characteristics in patients ≥18 years undergoing autologous (auto) or allogeneic (allo) HCT for hematological malignancies. Assessments were performed as part of routine pre-HCT evaluations and then retrospectively analyzed. We additionally investigated the association of mental health distress indicators with frailty and the association between frailty and transplant outcomes including NRM and overall survival (OS) plus healthcare utilization. Patients undergoing HCT for hematological malignancies were analyzed (total n = 300; 162 auto, 138 allo). The overall prevalence of frailty was 18%, 21.7% among alloHCT, and 14.8% among autoHCT recipients, with similar distributions of frailty domains. Logistic regression analysis of the overall cohort revealed that older age was associated with an increased risk of frailty (odds ratio [OR] 1.37, 95% confidence interval [CI] [1.02-1.82]; P = 0.04). AlloHCT (OR 2.03, CI [1.07-3.84]; P = .03), and patient health questionnaire-9 (PHQ-9) (health depression) score ≥10 (OR 6.28, CI 1.93-20.43; P < .01) were each independently associated with pre-HCT frailty. In alloHCT patients, older age (OR 1.44, CI [1.00-2.06]; P = .05) was the only significant risk factor for pre-HCT frailty, while for autoHCT patients, only a higher PHQ-9 score was associated with frailty (OR 6.43, CI [1.34-30.82]; P = .02). For the whole cohort OS at 1 year was lower in frail recipients at 83% (95% CI, 70-91%) versus 92% (95% CI, 88-95%) in nonfrail (P = .04); with multivariate analysis showing higher risk of death in the frail group (hazard ratio [HR] 2.31, CI 0.97-5.46; P = .06). In the alloHCT cohort, multivariate analysis showed greater 1-year mortality in frail recipients (HR 2.55, CI [0.99-6.56]; P = .053). In the alloHCT recipients, we observed a 1-year NRM of 20% in frail patients versus 9% in nonfrail, and multivariate analysis showed a marginally higher risk of NRM in the frail group (HR 2.70, CI 0.90-8.10; P = .08). Frailty was not associated with higher risk of relapse in alloHCT or autoHCT recipients. Frail alloHCT patients experienced a longer initial hospital stay following HCT compared to nonfrail recipients (P < .01). We observed a high prevalence of pre-HCT frailty across all age groups, and identify older age is a risk factor for frailty, particularly in alloHCT recipients. Frailty is associated with a greater risk of NRM and lower survival which needs investigation in a larger cohort. Frailty associates with greater HCT complexity suggesting a need for early assessments and targeted interventions for this vulnerable population. Our findings suggest the utility of frailty and mental distress screening along with multidisciplinary interventions in pre-HCT to limit the morbidity of HCT.
衰弱是一种与毒性和非复发死亡率（NRM）增加相关的生理储备减少的表型，发生在造血细胞移植（HCT）受者中。在接受血液系统恶性肿瘤自体（auto）或异基因（allo）HCT 的患者中，HCT 前衰弱的发生率、预测因素和不良影响尚不清楚。我们评估了使用 Fried 标准定义的 HCT 前衰弱与年龄和基线特征之间的相关性，该标准适用于年龄≥18 岁的接受血液系统恶性肿瘤自体或异基因 HCT 的患者。评估是作为常规 HCT 前评估的一部分进行的，然后进行回顾性分析。我们还研究了心理健康困扰指标与衰弱的关系，以及衰弱与包括 NRM 和总生存（OS）加医疗保健利用在内的移植结果之间的关系。分析了接受血液系统恶性肿瘤 HCT 的患者（总 n=300；162 例自体，138 例异基因）。衰弱的总患病率为 18%，alloHCT 中的患病率为 21.7%，autoHCT 中的患病率为 14.8%，衰弱域的分布相似。对整个队列的 logistic 回归分析显示，年龄较大与衰弱风险增加相关（比值比 [OR] 1.37，95%置信区间 [CI] [1.02-1.82]；P=0.04）。alloHCT（OR 2.03，CI [1.07-3.84]；P=0.03）和患者健康问卷-9（PHQ-9）（健康抑郁）评分≥10（OR 6.28，CI 1.93-20.43；P<0.01）与 HCT 前衰弱独立相关。在 alloHCT 患者中，年龄较大（OR 1.44，CI [1.00-2.06]；P=0.05）是 HCT 前衰弱的唯一显著危险因素，而对于 autoHCT 患者，只有较高的 PHQ-9 评分与衰弱相关（OR 6.43，CI [1.34-30.82]；P=0.02）。对于整个队列，1 年时 OS 在衰弱组为 83%（95%CI，70-91%），而非衰弱组为 92%（95%CI，88-95%），两组间差异有统计学意义（P=0.04）；多因素分析显示衰弱组死亡风险更高（风险比 [HR] 2.31，CI 0.97-5.46；P=0.06）。在 alloHCT 队列中，多因素分析显示衰弱组 1 年死亡率更高（HR 2.55，CI [0.99-6.56]；P=0.053）。在 alloHCT 受者中，我们观察到衰弱患者的 1 年 NRM 为 20%，而非衰弱患者为 9%，多因素分析显示衰弱组的 NRM 风险略高（HR 2.70，CI 0.90-8.10；P=0.08）。衰弱与 alloHCT 或 autoHCT 受者的复发风险增加无关。与非衰弱受者相比，衰弱的 alloHCT 患者在 HCT 后初始住院时间更长（P<0.01）。我们观察到衰弱在所有年龄组中都有很高的发生率，并且发现年龄较大是衰弱的一个危险因素，特别是在 alloHCT 受者中。衰弱与 NRM 风险增加和生存降低相关，这需要在更大的队列中进行研究。衰弱与 HCT 复杂性增加相关，提示需要对这一脆弱人群进行早期评估和针对性干预。我们的研究结果表明，在 HCT 前进行衰弱和心理健康筛查以及多学科干预可以减少 HCT 的发病率。
