Sorror Mohamed L, Gooley Ted A, Storer Barry E, Gerds Aaron T, Sekeres Mikkael A, Medeiros Bruno C, Wang Eunice S, Shami Paul J, Adekola Kehinde, Luger Selina, Baer Maria R, Rizzieri David A, Wildes Tanya M, Koprivnikar Jamie, Smith Julie, Garrison Mitchell, Kojouri Kiarash, Schuler Tammy A, Leisenring Wendy M, Onstad Lynn E, Becker Pamela S, McCune Jeannine S, Lee Stephanie J, Sandmaier Brenda M, Appelbaum Frederick R, Estey Elihu H
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
Blood. 2023 Jan 19;141(3):295-308. doi: 10.1182/blood.2022016916.
We designed a prospective, observational study enrolling patients presenting for treatment of acute myeloid leukemia (AML) at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), and function in: the entire cohort, those aged ≥65 years, those with high comorbidity burden, intermediate cytogenetic risk, adverse cytogenetic risk, and first complete remission with or without measurable residual disease. Patient were assessed 8 times over 2 years. Time-dependent regression models were used. Among 692 patients that were evaluable, 46% received HCT with a 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in most subgroups. Although function, social life, performance status, and depressive symptoms were better for those selected for HCT, these health advantages were lost after receiving HCT. Recipients and nonrecipients of HCT similarly ranked and expected cure as main goal of therapy, whereas physicians had greater expectations for cure than the former. Accounting for health impairments negates survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is mostly owing to selection of the healthier candidates. Considering patients' overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT. This trial was registered at www.clinicaltrials.gov as #NCT01929408.
我们设计了一项前瞻性观察性研究,纳入了在13家机构接受急性髓系白血病(AML)治疗的患者,以分析造血细胞移植(HCT)与生存、生活质量(QOL)以及以下方面功能之间的关联:整个队列、年龄≥65岁的患者、合并症负担高的患者、中等细胞遗传学风险的患者、不良细胞遗传学风险的患者以及有或无可测量残留病的首次完全缓解患者。在2年时间里对患者进行了8次评估。使用了时间依赖性回归模型。在692例可评估患者中,46%接受了HCT,2年生存率为58%。在未调整的模型中,HCT与大多数亚组中降低的死亡风险相关。然而,在考虑了与死亡率增加相关的协变量(年龄、合并症负担、疾病风险、虚弱、生活质量受损、抑郁和功能受损)后,HCT与更长生存之间的关联在大多数亚组中消失了。尽管接受HCT患者的功能、社交生活、表现状态和抑郁症状更好,但接受HCT后这些健康优势丧失了。HCT接受者和非接受者同样将治愈列为治疗的主要目标,而医生对治愈的期望高于前者。考虑到健康损害会抵消AML患者接受HCT的生存益处,这表明未调整观察到的益处主要归因于选择了更健康的候选者。考虑到患者对治愈的总体期望以及HCT的生活质量负担,促使需要进行随机试验以确定HCT的最佳候选者。该试验已在www.clinicaltrials.gov上注册,编号为#NCT01929408。