背景:第二次异基因造血细胞移植(HCT2)可能治疗成人AML或骨髓增生异常肿瘤(MDS)/首次同种异体移植(HCT1)后复发的AML,但预后因素的特征不明确.
目的:提供一个大型单中心队列中HCT2结局和相关预后因素的详细分析,重点是确定复发和非复发死亡率(NRM)的预测因子。
方法:我们研究了2006年4月至2022年6月期间在单一机构接受HCT2治疗的≥18岁的成年人复发AML(n=73)或MDS/AML(n=8)。
结果:幸存者的中位随访时间为74.0(范围:10.4-187.3)个月,有30例复发和57例死亡,其中29个是NRM事件,有助于复发的估计,总生存期(OS),无复发生存率(RFS),和NRM。复发的三年估计,RFS,和OS为37%(95%置信区间:27-48%),32%(23-44%),和35%(26-47%)。100天和18个月时的NRM率为20%(12-29%)和28%(19-39%)。不同患者亚群的结果明显不同,对于患有活动性疾病(即骨髓和/或髓外疾病的形态学证据)的HCT2患者,对于HCT1术后≤6个月复发的患者,以及HCT特异性合并症指数(HCT-CI)或治疗相关死亡率(TRM)评分较高的患者.经过多变量调整后,与无可测量残留病(MRD)多参数流式细胞术证据的形态学缓解患者移植相比,活动性疾病与较高的复发风险(HR=3.19,p=0.006)和较短的RFS(HR=2.41,p=0.008)以及OS(HR=2.17,p=0.027)相关.同样,首次同种异体移植后<6个月的无复发间隔与较高的复发风险(HR=5.86,p<0.001)和较短的RFS(HR=2.86;p=0.001)和OS(HR=2.45,p=0.003)相关.此外,高HCT-CI评分与NRM增加相关(HR=4.30,p=0.035),和较短的RFS(HR=3.87,p=0.003)和OS(HR=3.74,p=0.006)。同样,较高的TRM评分与复发风险增加(HR=2.27;p=0.024)和NRM(HR=2.01,p=0.001)相关,和较差的RFS(HR=1.90p=0.001)和OS(HR=1.88,p=0.001)。
结论:在接受HCT2治疗3年后,AML或MDS/AML复发的患者中有相当一部分存活且无白血病。我们的研究将HCT2时的活动性白血病和HCT1后的早期复发确定为主要的不良预后因素。强调患者亚组特别需要新的治疗方法,并支持使用HCT-CI和TRM评分进行预后。
Second allogeneic hematopoietic cell transplantation (HCT2) is potentially curative for adults with acute myeloid leukemia (AML) or myelodysplastic neoplasm (MDS)/AML experiencing relapse after a first allograft (HCT1), but prognostic factors for outcomes are poorly characterized. To provide a detailed analysis of HCT2 outcomes and associated prognostic factors in a large single-center cohort, with a focus on identifying predictors of relapse and nonrelapse mortality (NRM). We studied adults ≥18 years who underwent HCT2 at a single institution between April 2006 and June 2022 for relapsed AML (n = 73) or MDS/AML (n = 8). With a median follow-up among survivors of 74.0 (range: 10.4 to 187.3) months, there were 30 relapses and 57 deaths, of which 29 were NRM events, contributing to the estimates for relapse, overall survival (OS), relapse-free survival (RFS), and NRM. Three-year estimates for relapse, RFS, and OS were 37% (95% confidence interval: 27% to 48%), 32% (23% to 44%), and 35% (26% to 47%). The rate of NRM at 100 days and 18 months was 20% (12% to 29%) and 28% (19% to 39%). Outcomes differed markedly across patient subsets and were substantially worse for patients who underwent HCT2 with active disease (ie, morphologic evidence of bone marrow and/or extramedullary disease), for patients who relapsed ≤6 months after HCT1, and for patients with higher HCT-specific Comorbidity Index (HCT-CI) or treatment-related mortality (TRM) scores. After multivariable adjustment, active disease was associated with a higher risk of relapse (hazard ratio [HR] = 3.19, P = .006) and shorter RFS (HR = 2.41, P = .008) as well as OS (HR = 2.17, P = .027) compared to transplant in morphologic remission without multiparameter flow cytometric evidence of measurable residual disease. Similarly, a relapse-free interval ≤6 months after the first allograft was associated with higher risk of relapse (HR = 5.86, P < .001) and shorter RFS (HR = 2.86; P = .001) and OS (HR = 2.45, P = .003). Additionally, a high HCT-CI score was associated with increased NRM (HR = 4.30, P = .035), and shorter RFS (HR = 3.87, P = .003) and OS (HR = 3.74, P = .006). Likewise, higher TRM scores were associated with increased risk of relapse (HR = 2.27; P = .024) and NRM (HR = 2.01, P = .001), and inferior RFS (HR = 1.90 P = .001) and OS (HR = 1.88, P = .001). A significant subset of patients with AML or MDS/AML relapse after HCT1 are alive and leukemia-free 3 years after undergoing HCT2. Our study identifies active leukemia at the time of HCT2 and early relapse after HCT1 as major adverse prognostic factors, highlighting patient subsets in particular need of novel therapeutic approaches, and supports the use of the HCT-CI and TRM scores for outcome prognostication.