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单中心经验表明,供者淋巴细胞输注可能促进高危急性淋巴细胞白血病患儿的长期生存。

Single-center experience suggests donor lymphocyte infusion may promote long-term survival in children with high-risk acute lymphoblastic leukemia.

机构信息

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.

Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.

出版信息

Pediatr Blood Cancer. 2019 Nov;66(11):e27950. doi: 10.1002/pbc.27950. Epub 2019 Jul 31.

Abstract

BACKGROUND

Donor lymphocyte infusion (DLI) is often used to treat leukemic relapse after hematopoietic cell transplantation (HCT). However, the relationship between outcomes and distinct DLI cellular composition has not been previously reported. Additionally, there are limited published data on efficacy in pediatrics. We evaluated whether DLI cellular content and development of graft-versus-host disease (GVHD) impacted disease and influenced overall survival (OS) in children receiving DLI for recurrent leukemia.

METHODS

We performed an Institutional Review Board-approved, retrospective study investigating all consecutive DLIs given to patients at the Children's Hospital of Wisconsin between 1980 and 2018. Analyses were conducted using Mann-Whitney, Fisher exact, and chi-square tests.

RESULTS

Thirty patients ≤20 years old with hematologic malignancies (myeloid [AML/MDS/CML/JMML], n = 23; lymphoid [ALL], n = 7) received DLI to treat post-transplant relapse. We found no significant difference in OS or development of GVHD based on CD3, CD4, CD8, CD56, or CD19 DLI cellular composition. With a median follow-up of 0.69 (range, 0.04-16.61) years, OS at five years was 32% ± 9%.  The lymphoid group had a five-year survival rate at 71% ± 17% compared with the myeloid group at 22% ± 9%, although not statistically significant (P = 0.11).  The development of GVHD did not affect OS (P = 0.62).

CONCLUSION

Here, we report a single-center, long-term experience of pediatric DLIs. Surprisingly, many children with ALL were able to achieve durable remissions. Although cellular composition did not have a significant effect on GVHD or OS in our small study, engineering DLI products to maximize specific effector cell populations could be one strategy to improve efficacy.

摘要

背景

供者淋巴细胞输注(DLI)常用于治疗造血细胞移植(HCT)后白血病复发。然而,DLI 细胞组成与治疗结果之间的关系尚未见报道。此外,儿科的相关研究数据也很有限。我们评估了 DLI 细胞含量和移植物抗宿主病(GVHD)的发展是否影响疾病,并影响接受 DLI 治疗复发性白血病儿童的总生存(OS)。

方法

我们进行了一项机构审查委员会批准的回顾性研究,调查了 1980 年至 2018 年期间威斯康星州儿童医院所有连续接受 DLI 的患者。采用 Mann-Whitney、Fisher 精确和卡方检验进行分析。

结果

30 名≤20 岁的血液系统恶性肿瘤(髓系[AML/MDS/CML/JMML],n = 23;淋巴系[ALL],n = 7)患者接受 DLI 治疗移植后复发。我们发现,根据 CD3、CD4、CD8、CD56 或 CD19 DLI 细胞组成,OS 或 GVHD 的发展无显著差异。中位随访时间为 0.69 年(范围,0.04-16.61 年),5 年 OS 率为 32%±9%。淋巴系组的 5 年生存率为 71%±17%,而髓系组为 22%±9%,尽管无统计学意义(P = 0.11)。GVHD 的发生并不影响 OS(P = 0.62)。

结论

在此,我们报告了一项单中心、长期的儿科 DLI 经验。令人惊讶的是,许多 ALL 患儿能够获得持久缓解。尽管在我们的小研究中,细胞组成对 GVHD 或 OS 没有显著影响,但工程化 DLI 产品以最大限度地增加特定效应细胞群体可能是提高疗效的一种策略。

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