Favorable Immune Reconstitution in Patients Administered Anti-Thymocyte Globulin (ATG) Early in the Course of Reduced Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation

胸腺球蛋白 抗胸腺细胞球蛋白 医学 移植 内科学 移植物抗宿主病 胃肠病学 队列 氟达拉滨 全身照射 免疫学 梅尔法兰 造血干细胞移植 阿勒姆图祖马 化疗 环磷酰胺 他克莫司
作者
Viktoriya Zelikson,Natasha Raman,Anatevka Rebiero,Elizabeth Krieger,Catherine Roberts,Gary Simmons,Amir A. Toor
出处
期刊:Blood [Elsevier BV]
卷期号:136 (Supplement 1): 16-17
标识
DOI:10.1182/blood-2020-138581
摘要

Anti-thymocyte globulin (ATG) mitigates graft vs host disease (GVHD) risk in patients undergoing allogeneic hematopoietic cell transplantation (HCT). Due to T cell depletion there remains a concern that ATG administration may be associated with an increased risk of malignancy, relapse, and infection in recipients of reduced intensity conditioning (RIC). It was hypothesized that ATG infusion early in the course of conditioning will promote rapid immune reconstitution because of lower levels at the time of graft infusion and will thus help to improve clinical outcomes in RIC. Rabbit ATG (Thymoglobulin, Sanofi Aventis) was administered from day (d) -9 to -7 to HLA matched-unrelated (MUD; 5 mg/kg in divided doses) and -related (MRD; 3.5 mg/kg) donor transplant recipients conditioned with Fludarabine and Melphalan (ATG -9 cohort; N=36). Immune reconstitution and clinical outcomes were compared with a historical control group of patients who received the same doses of ATG from d-3 to -1 (ATG -3 cohort; N=28). Standard GVHD prophylaxis with calcineurin inhibitor and antimetabolite was administered, with CMV and EBV monitoring. ATG -9 cohort had more, MUD recipients 80% vs. 64%; myeloid malignancy (AML, MDS, MPD) 83% vs. 35%. Age (56 vs. 57), graft type (97 vs. 92% PBSC) and CD34+cell dose infused (4.8 vs 4.7 E6/KG) were similar. Immune reconstitution was uniformly superior in ATG -9 cohort, with significantly higher absolute monocyte counts (AMC) at d30, 60 and 90 (P<0.001), as well as higher donor derived CD3+ (ddCD3+) and CD3+/8+ cell counts at d60 and 90 (P<0.01), and CD3+/4+ cells at d90 (P=<0.05). T cell - monocyte interactions were modelled as 2 dimensional vectors in the immune phase space, (Figure 1) with a consistently higher vector magnitude observed in ATG-9 cohort (P<0.01). Rate of T cell reconstitution was determined by calculating the derivative of ddCD3+ cell count as a function of time (dT/dt) post-transplant (Figure 2) and was generally higher in the ATG-9 cohort, particularly at d60. With a median follow up of 14.9 months in the ATG-9 cohort, and 47.2 months in the ATG -3 cohort, there is a non-significant trend for improved survival (72.2% vs. 46.4% at 2 years) and relapse (19.4% vs. 35.7% at 2 years) in the ATG -9 cohort. TRM and acute GVHD were similar, with a trend towards greater risk for chronic GVHD in the ATG -9 cohort, albeit of a lower severity. Given the relatively low number of patients in each cohort, the effect of immune reconstitution on clinical outcomes was evaluated in the pooled population. Survival was improved in those with AMC and ddCD3+ cell counts >200/µL at d60 (P=0.004 & 0.016 respectively), and in patients with T cell - monocyte vector magnitude > median (577.48/µL) at that time (P= 0.008), as well as in those with a calculated dT/dt > median (1.96 cells/µL/day) at d45 (P=0.047). The latter was also associated with a reduction in relapse rate (P=0.04), as was ddCD8+ cell count >145/µL at d60 (P=0.04). Acute GVHD risk was increased when dT/dt was >median (7.60 cells/µL/day) at d15 (P=0.0095), and correspondingly with T cell - monocyte vector magnitude > median (1033.3/µL) at d30 (P=0.017). In conclusion, this retrospective study demonstrates that equal doses of ATG administered earlier (d -9 to -7 as opposed to d-1 to -3) during conditioning yield more rapid and robust immune reconstitution. Monocyte and ddCD3+ cell recovery kinetics have a favorable impact on survival and relapse risk following HLA matched HCT. Patients at risk for acute GVHD may be identified as early as d15 post HCT by analyzing ddCD3+ cell reconstitution kinetics. Different ATG administration schedules should be studied prospectively with a focus on immune reconstitution kinetics as a determinant of clinical outcomes. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Rabbit anti-thymocyte globulin for GVHD prophylaxis.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
2秒前
2秒前
潇湘雪月发布了新的文献求助10
3秒前
3秒前
3秒前
4秒前
感动黄豆发布了新的文献求助10
4秒前
hhhblabla应助东方红采纳,获得10
6秒前
Poker应助sb采纳,获得10
7秒前
Ginger发布了新的文献求助10
7秒前
吃骨头的猫完成签到,获得积分10
7秒前
小李完成签到,获得积分10
7秒前
7秒前
8秒前
明芬发布了新的文献求助30
10秒前
10秒前
Smile完成签到,获得积分10
10秒前
Chaoe完成签到,获得积分10
13秒前
建国发布了新的文献求助10
14秒前
闪闪w发布了新的文献求助10
17秒前
淡烟流水完成签到,获得积分10
17秒前
俏皮芷蕊完成签到,获得积分10
18秒前
完美世界应助忐忑的阑香采纳,获得10
18秒前
华仔应助兴奋千兰采纳,获得10
23秒前
Ginger完成签到,获得积分10
24秒前
潇湘雪月发布了新的文献求助10
27秒前
科研通AI5应助科研通管家采纳,获得10
29秒前
29秒前
佳琳有乐完成签到,获得积分10
29秒前
29秒前
小蘑菇应助科研通管家采纳,获得10
29秒前
大模型应助科研通管家采纳,获得10
29秒前
CHAosLoopy应助科研通管家采纳,获得10
30秒前
桐桐应助科研通管家采纳,获得10
30秒前
今后应助cccyq采纳,获得10
30秒前
烟花应助科研通管家采纳,获得30
30秒前
情怀应助科研通管家采纳,获得10
30秒前
30秒前
隐形曼青应助科研通管家采纳,获得10
30秒前
在水一方应助科研通管家采纳,获得30
30秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989115
求助须知:如何正确求助?哪些是违规求助? 3531367
关于积分的说明 11253688
捐赠科研通 3269986
什么是DOI,文献DOI怎么找? 1804868
邀请新用户注册赠送积分活动 882078
科研通“疑难数据库(出版商)”最低求助积分说明 809105