Supplementary Material for: Outcomes of Patients with Myeloid Malignancies and Cardiovascular Disease Undergoing Allogeneic Stem Cell Transplantation

Introduction/Background: Reduced-intensity conditioning (RIC) and non-myeloablative (NMA) regimens have enabled patients with cardiovascular disease (CVD) to undergo allogeneic stem cell transplantation (allo-HSCT). However, little is known about long-term outcomes, including cardiovascular (CV) complications.

Methods: We retrospectively studied 99 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who underwent allo-HSCT between September 1, 2013, and November 30, 2020. Overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), cumulative incidence of relapse and cumulative incidence of acute and chronic graft-versus host disease (GvHD) were compared in patients with and without CV risk factors or disease.

Results: Preexisting CVD was present in 34 of 99 patients (34%). CVD patients more commonly had reduced-intensity conditioning (91% vs 60%, p=0.001) and unrelated donors (56% vs 35%, p=0.04). Early adverse cardiac events occurred more frequently in the CVD vs. no-CVD group (38% vs 14%), particularly arrhythmias (21% vs 5%; p= 0.04). CVD patients tended to have poorer OS and PFS outcomes [HR=1.98, (1.00, 3.92); HR= 1.89, (0.96-3.72), respectively]. OS rate at 1, 2 and 3 years for CVD vs. no-CVD patients was 66% vs. 72%, 55% vs. 64%, and 46% vs. 62% respectively. Causes of death in the CVD and no-CVD groups were infections (53% vs 28%), relapsed disease (32% vs 52%), and CV events (10% vs 3%).

Conclusion: Based on these data, predictive models to identify patients with CVD with higher risk of post-alloSCT complications and mortality and strategies to mitigate these risks should be developed.

研究背景与引言：减低强度预处理（reduced-intensity conditioning, RIC）方案与非清髓性（non-myeloablative, NMA）疗法已使心血管疾病（cardiovascular disease, CVD）患者得以接受异基因造血干细胞移植（allogeneic stem cell transplantation, allo-HSCT）。然而，目前针对此类患者的长期预后（包括心血管并发症）仍知之甚少。

研究方法：本研究回顾性分析了2013年9月1日至2020年11月30日间接受异基因造血干细胞移植的99例连续入组的急性髓系白血病（acute myeloid leukemia, AML）或骨髓增生异常综合征（myelodysplastic syndrome, MDS）患者。对比了合并与未合并心血管危险因素或心血管疾病的患者的总生存期（overall survival, OS）、无进展生存期（progression-free survival, PFS）、非复发死亡率（non-relapse mortality, NRM）、复发累积发生率，以及急性与慢性移植物抗宿主病（graft-versus host disease, GvHD）的累积发生率。

研究结果：99例患者中共有34例（34%）存在基础心血管疾病。合并心血管疾病的患者更常采用减低强度预处理方案（91% vs 60%，p=0.001），且更多使用无关供者（56% vs 35%，p=0.04）。与未合并心血管疾病的患者相比，合并心血管疾病组的早期不良心脏事件发生率更高（38% vs 14%），尤以心律失常更为显著（21% vs 5%；p=0.04）。合并心血管疾病患者的总生存期与无进展生存期均表现出较差的趋势[风险比（HR）=1.98，95%置信区间：1.00~3.92；风险比（HR）=1.89，95%置信区间：0.96~3.72]。合并与未合并心血管疾病患者的1年、2年、3年总生存率分别为66% vs 72%、55% vs 64%、46% vs 62%。两组患者的死亡原因分别为感染（53% vs 28%）、疾病复发（32% vs 52%）以及心血管事件（10% vs 3%）。

研究结论：基于本研究数据，应开发预测模型以识别异基因造血干细胞移植术后并发症与死亡风险更高的心血管疾病患者，并制定相应的风险防控策略。