Abstract A48: Aging-related, Senescence-associated Secretory Phenotype and Allogeneic Hematopoietic Cell Transplantation Outcomes in Older Adults

IF 11.5 Q1 HEMATOLOGY

Blood Cancer Discovery Pub Date : 2023-05-01 DOI:10.1158/2643-3249.aml23-a48

R. Lin, P. Wong, J. Flynn, Erika R Ritter, Caleb Ho, J. Ruiz, A. Jakubowski, E. Papadopoulos, B. Shaffer, H. Castro-Malaspina, C. Cho, Doris Ponce, J. Barker, R. Tamari, C. Sauter, B. Gyurkocza, M. V. D. van den Brink, J. Young, M. Perales, S. Devlin, S. Giralt

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引用次数: 0

Abstract

Introduction: Older adults with hematologic malignancies such as AML and MDS increasingly undergo allogeneic hematopoietic cell transplantation (alloHCT). The impact of the aging host environment, especially cellular senescence, remains unexplored, however. Objectives: We hypothesize that pre-transplant senescence-associated secretary phenotype (SASP) is associated with alloHCT outcomes among older patients and tested it in this biomarker correlative study. Methods: We measured ten SASP-related cytokines (IFNγ, IL1β, IL2, IL4, IL6, IL8, IL10, IL12, IL13, and TNFα, and C-reactive protein (CRP) from pre-transplant plasma samples of 155 patients (>50 years) who had undergone alloHCT at MSKCC from 2011 to 2019 for acute leukemias and other myeloid malignancies. Expression of aging biomarker p16 was measured on a subset of patients by immunohistochemistry. Results and Discussion: The median age was 64.1 years (IQR 58.3 – 67.8). Diseases included 57% acute leukemias (AML and ALL) and 43% MDS/MPN. KPS was <90 in 43% and HCT-CI was >3 in 53% of patients. With median follow-up of 61 months for survivors, the 5-year OS and PFS is 50% and 46%, respectively. The 2-year cumulative incidence of non-relapse mortality (NRM) and relapse is 18% and 31%, respectively. At the baseline, these SASP-related cytokines have variable degree of association with KPS, chronologic age, and disease risk. IL2 trended toward significant positive association with OS (HR 1.19, 95% CI 1-1.43, p=0.052) and was significantly associated with PFS (HR 1.21, 95% CI 1.02-1.44, p=0025) in univariate analysis, but not in multivariate analysis after adjusting for clinical characteristics. No cytokine was associated with NRM. IL2 and IL4 were associated with relapse in univariate but not multivariate analysis. Several cytokines including IL12 p70, IL13, IL4, and TNFα were associated with 100d grade II-IV acute GVHD in patients who received CNI-based GVHD prophylaxis. In summary, we found potential association of SASP-related cytokines with patient characteristics and transplant outcomes. We aim to validate these findings and examine their therapeutic potential to improve alloHCT outcomes. Citation Format: Richard J Lin, Phillip Wong, Jessica R Flynn, Erika R Ritter, Caleb Ho, Josel D Ruiz, Ann A Jakubowski, Esperanza B Papadopoulos, Brian C Shaffer, Hugo R Castro-Malaspina, Christina J Cho, Doris R Ponce, Juliet N Barker, Roni Tamari, Craig S Sauter, Boglarka Gyurkocza, Marcel van den Brink, James W Young, Miguel-Angel Perales, Sean M Devlin, Sergio A Giralt. Aging-related, Senescence-associated Secretory Phenotype and Allogeneic Hematopoietic Cell Transplantation Outcomes in Older Adults [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A48.

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A48:老年人与衰老相关的分泌表型和异基因造血细胞移植的结果

引言：患有AML和MDS等血液系统恶性肿瘤的老年人越来越多地接受异基因造血细胞移植（alloHCT）。然而，衰老宿主环境的影响，尤其是细胞衰老，尚未得到探索。目的：我们假设移植前衰老相关秘书表型（SASP）与老年患者的alloHCT结果相关，并在这项生物标志物相关研究中进行了测试。方法：我们从2011年至2019年在MSKCC接受同种异体HCT治疗的155名患者（50岁以上）的移植前血浆样本中测量了10种SASP相关细胞因子（IFNγ、IL1β、IL2、IL4、IL6、IL8、IL10、IL12、IL13和TNFα）和C反应蛋白（CRP）。衰老生物标志物p16的表达通过免疫组织化学在一组患者中进行测量。结果与讨论：中位年龄为64.1岁（IQR 58.3–67.8）。疾病包括57%的急性白血病（AML和ALL）和43%的MDS/MPN。53%的患者KPS为3。幸存者的中位随访时间为61个月，5年OS和PFS分别为50%和46%。非复发死亡率（NRM）和复发的2年累计发病率分别为18%和31%。在基线时，这些SASP相关细胞因子与KPS、时间年龄和疾病风险有不同程度的相关性。在单变量分析中，IL2倾向于与OS显著正相关（HR 1.19，95%CI 1-1.43，p=0.052），并与PFS显著相关（HR 1.21，95%CI 1.02-1.44，p=0.025），但在调整临床特征后的多变量分析中没有。无细胞因子与NRM相关。在单因素分析中，IL2和IL4与复发相关，但与多因素分析无关。在接受基于CNI的GVHD预防的患者中，包括IL12p70、IL13、IL4和TNFα在内的几种细胞因子与100d II-IV级急性GVHD相关。总之，我们发现SASP相关细胞因子与患者特征和移植结果之间存在潜在联系。我们的目的是验证这些发现，并检查其改善alloHCT结果的治疗潜力。引文格式：Richard J Lin、Phillip Wong、Jessica R Flynn、Erika R Ritter、Caleb Ho、Josel D Ruiz、Ann A Jakubowski、Esperanza B Papadopoulos、Brian C Shaffer、Hugo R Castro Malaspina、Christina J Cho、Doris R Ponce、Juliet N Barker、Roni Tamari、Craig S Sauter、Boglarka Gyurkocza、Marcel van den Brink、James W Young、Miguel Angel Perales、Sean M Devlin、Sergio A Giralt。老年人衰老相关、衰老相关分泌表型和异基因造血细胞移植结果[摘要]。载：AACR特别会议论文集：急性髓细胞白血病和骨髓增生异常综合征；2023年1月23日至25日；德克萨斯州奥斯汀。费城（PA）：AACR；血液癌症Discov 2023；4（3_Suppl）：摘要编号A48。

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来源期刊

Blood Cancer Discovery Multiple-

CiteScore

12.70

自引率

1.80%

发文量

139

期刊介绍： The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes. The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence. Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.