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血液系统恶性肿瘤患者供者淋巴细胞输注后的结局:供者特征至关重要

英文原题:Outcomes After Donor Lymphocyte Infusion in Patients With Hematological Malignancies: Donor Characteristics Matter.

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Outcomes After Donor Lymphocyte Infusion in Patients With Hematological Malignancies: Donor Characteristics Matter.

PubMed 2022/01/31(内容时间) Transplant Cell Ther Q1 · IF 4.7(JCR 2025)

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中文摘要

在T细胞清除的背景下,未能实现完全供者嵌合(FDC)会导致移植物丢失和疾病复发的风险增高。供者淋巴细胞输注(DLI)是一种过继免疫治疗,用于减低强度预处理异基因造血干细胞移植(HSCT)后的混合嵌合(MC)或复发性疾病。

然而,对于与实现FDC或疾病缓解相关的因素知之甚少。我们开展了一项纳入100例成人患者的回顾性研究,以识别可预测实现FDC和疾病缓解的患者及供者因素,并描述DLI后的并发症。DLI的指征为61例患者的T细胞MC和39例患者的复发性疾病。40例(65.6%)MC患者实现了T细胞完全供者嵌合(T-FDC),其中供者为女性的患者(81.5%对52.9%,P = .004)和巨细胞病毒阴性的患者(76.5%对52%,P = .004)缓解率更高。

然而,只有供者较年轻(<30岁)的患者与供者较年长者相比(94.4%对53.5%,P = .013),以及DLI后实现未分离全血(UWB)FDC的患者(76.6%对28.6%,P < .001)具有生存获益,并随后获得更好的无移植物抗宿主病(GvHD)/无复发生存。39例复发性疾病患者中有19例(48.7%)在DLI后实现缓解。在该队列中,实现T-FDC对疾病控制产生了有利影响(76.7%对12.5%,P = .012)并改善了生存(45.5%对12.5%,P = .007)。在整个人群中,DLI后第100天急性GvHD(aGvHD)的累积发生率为23%,DLI后1年慢性GvHD(cGvHD)的累积发生率为22%。

在整个人群中,供者年龄也是aGvHD的决定因素,因为供者较年轻的患者aGvHD发生率较低(8% versus 36%,P = .021)。转为T-FDC的患者更可能发生cGvHD(34% versus 10.3%,P = .025)。在决定HSCT方案时,供者特征正被越来越多地纳入考虑。在规划HSCT时,应考虑供者年龄,以及DLI的剂量和安排。根据我们的经验,这应与T/UWB嵌合状态一起进行,以在相关毒性较小的情况下实现最大临床获益。从干细胞登记库中选择较年轻的男性供者,可尽量降低GvHD风险并改善生存。

展开英文摘要原文

In the context of T-cell depletion, failing to achieve full donor chimerism (FDC) entails higher risk of graft loss and disease relapse. Donor lymphocyte infusion (DLI) is an adoptive immunotherapy for mixed chimerism (MC) or relapsed disease after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, little is known of factors associated with attaining FDC or disease remission.

We carried out a retrospective study with 100 adult patients to identify patient and donor factors that can predict achievement of FDC and disease remission and describe complications after DLI. Indications for DLI were T-cell MC in 61 patients and relapsed disease in 39 patients. Forty patients (65. 6%) with MC attained T-full donor chimerism (T-FDC), with higher responses seen in patients whose donors were female (81. 5% versus 52. 9%, P = . 004) and cytomegalovirus negative (76. 5% versus 52%, P = . 004).

However, only patients with younger donors (<30 years old) compared to older donors (94. 4% versus 53. 5%, P = . 013) and those attaining unfractionated whole blood (UWB) FDC after DLI (76. 6% versus 28. 6%, P < . 001) had a survival benefit and subsequently a better graft-versus-host disease (GvHD)-free/relapse-free survival. Nineteen of 39 patients (48. 7%) with relapsed disease achieved remission after DLI. In this cohort, attaining T-FDC impacted favorably in disease control (76. 7% versus 12. 5%, P = . 012) and improved survival (45. 5% versus 12. 5%, P = . 007). In the whole population, the cumulative incidence of acute GvHD (aGvHD) at day 100 after DLI was 23%, and chronic GvHD (cGvHD) at 1 year after DLI was 22%.

In the whole population, donor age was also a determining factor for aGvHD, because patients with younger donors had a lower incidence of aGvHD (8% versus 36%, P = . 021). The cGvHD was more likely to occur in patients who converted to T-FDC (34% versus 10. 3%, P = . 025). Donor characteristics are increasingly considered when deciding approaches for HSCT.

Donor age should be considered when planning HSCT, as well as doses and scheduling of DLI. As per our experience, this should be done alongside T/UWB chimerism to achieve the maximal clinical benefit with less associated toxicity. Selection of younger male donors from stem cell registries can minimize the risk of GvHD and improve survival.

论文信息

作者
Ros-Soto J、Snowden JA、Szydlo R、Nicholson E、Madrigal A、Easdale S、Potter M、Ethell M
单位
Haematology Department, Hammersmith Hospital, Imperial College Healthcare Trust, London, United Kingdom; Anthony Nolan Research Institute, Royal Free Hospital and University College London, London, United Kingdom. Electronic address: jose.rossoto@nhs.net.United Kingdom
期刊
Transplantation and cellular therapy2022 Apr
原文标识
PubMed 35104660 · DOI 10.1016/j.jtct.2022.01.022