Uchibori Yusuke, Kurosawa Shuhei, Najima Yuho, Haraguchi Kyoko, Sadato Daichi, Hirama Chizuko, Sadaga Yasutaka, Kondo Kaori, Kato Chika, Sakai Satoshi, Kambara Yasuhiro, Ouchi Fumihiko, Shimabukuro Masashi, Jinguji Atsushi, Shingai Naoki, Toya Takashi, Shimizu Hiroaki, Kobayashi Takeshi, Harada Hironori, Harada Yuka, Okuyama Yoshiki, Doki Noriko
Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Department of Transfusion and Cell Therapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Front Immunol. 2025 Jan 29;16:1521895. doi: 10.3389/fimmu.2025.1521895. eCollection 2025.
Donor lymphocyte infusion (DLI) is a therapeutic approach for relapse after hematopoietic stem cell transplantation (HSCT). Despite their reported efficacy, the evolution of DLI practices over time remains underexplored.
This study provided a comprehensive analysis of DLI strategies and outcomes over 30 years at a single institution. A retrospective analysis was conducted on 75 patients who underwent DLI for disease relapse between April 1994 and March 2024. The primary endpoint was the 3-year overall survival (OS) rate after DLI. Secondary endpoints included the 100-day complete remission (CR) rate and incidence of acute graft-versus-host disease (GVHD).
The median age at the first DLI was 49 years (range, 20-69 years). The most common underlying diseases in all 75 cases were acute myeloid leukemia (AML, n = 46) and myelodysplastic syndromes (MDS, n = 12). Until 2014, DLI was only performed in patients with AML (n = 14), MDS (n = 2), or chronic myeloid leukemia (n = 5). However, since 2015, patients with various diseases, including lymphoid malignancies, have also undergone DLI. Azacitidine was the most frequently used combination therapy with DLI (n = 34). Regimens including venetoclax and FLT3 inhibitors have been commonly used since 2019 (n = 18). The 3-year OS rate was 29.1% (95% CI, 18.8-40.2%). Factors negatively influencing OS included age ≥50 years and a high or very high refined disease risk index. The 100-day CR rate was 52.1%, and acute GVHD occurred in 25.3% of the patients, with no strong correlation between GVHD incidence and CR achievement. Among 18 patients who underwent three or more DLIs since 2018, 88.9% achieved remission following DLI or second HSCT, with a median follow-up of 949.5 days for survivors.
This study highlighted the evolving trends in DLI practices and the diversification of combination therapies. Future research should focus on further validating these findings and optimizing DLI protocols to improve patient outcomes.
供体淋巴细胞输注（DLI）是造血干细胞移植（HSCT）后复发的一种治疗方法。尽管其疗效已得到报道，但DLI实践随时间的演变仍未得到充分探索。
本研究对一家机构30年来的DLI策略和结果进行了全面分析。对1994年4月至2024年3月期间因疾病复发接受DLI的75例患者进行了回顾性分析。主要终点是DLI后的3年总生存率（OS）。次要终点包括100天完全缓解（CR）率和急性移植物抗宿主病（GVHD）的发生率。
首次DLI时的中位年龄为49岁（范围20 - 69岁）。所有75例患者中最常见的基础疾病是急性髓系白血病（AML，n = 46）和骨髓增生异常综合征（MDS，n = 12）。直到2014年，DLI仅在AML患者（n = 14）、MDS患者（n = 2）或慢性髓系白血病患者（n = 5）中进行。然而，自2015年以来，包括淋巴系统恶性肿瘤在内的各种疾病患者也接受了DLI。阿扎胞苷是与DLI联合使用最频繁的治疗方法（n = 34）。自2019年以来，包括维奈克拉和FLT3抑制剂的方案已被广泛使用（n = 18）。3年OS率为29.1%（95%CI，18.8 - 40.2%）。对OS有负面影响的因素包括年龄≥50岁以及高或非常高的精细疾病风险指数。100天CR率为52.1%，25.3%的患者发生了急性GVHD，GVHD发生率与CR达成之间无强相关性。在2018年以来接受三次或更多次DLI的18例患者中，88.9%在DLI或第二次HSCT后实现缓解，幸存者的中位随访时间为949.5天。
本研究突出了DLI实践的演变趋势以及联合治疗的多样化。未来的研究应集中在进一步验证这些发现并优化DLI方案以改善患者结局。
