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阿扎胞苷与供体淋巴细胞输注用于异基因造血干细胞移植后复发的急性髓系白血病和骨髓增生异常综合征患者:一项荟萃分析。

Azacitidine and donor lymphocyte infusion for patients with relapsed acute myeloid leukemia and myelodysplastic syndromes after allogeneic hematopoietic stem cell transplantation: A meta-analysis.

作者信息

Li Xuefeng, Wang Wen, Zhang Xin, Wu Yu

机构信息

Department of Hematology and Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China.

Chinese Evidence-based Medicine Center and Cochrane China Center, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Front Oncol. 2022 Aug 5;12:949534. doi: 10.3389/fonc.2022.949534. eCollection 2022.

Abstract

BACKGROUND

For patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), azacitidine with donor lymphocyte infusion (DLI) is a feasible option to perform a preemptive or salvage treatment. However, its efficacy lacked comprehensive analysis, and this study aimed to fill this gap.

METHODS

We searched potential studies in PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials. Thirteen studies involving 811 patients were analyzed. The inverse variance method was used to calculate the pooled proportion and 95% confidence interval (CI). Subgroup analysis was performed to explore the source of heterogeneity.

RESULTS

The rate of pooled complete remission + partial remission (CR + PR), CR, and 2-year overall survival (OS) were 30% (95% CI: 22%-39%), 21% (95% CI: 16%-28%), and 31% (95% CI: 27%-35%), respectively. The pooled acute graft-versus-host disease (GvHD) and chronic GvHD rates were 15% (95% CI: 9%-23%) and 14% (95% CI: 8%-23%), respectively. Adverse cytogenetics and a higher percentage of bone marrow (BM) blasts at relapse were correlated with worse CR + PR and CR (interaction p < 0.05). Higher 2-year OS was found in patients with lower BM blasts at relapse or a longer time from allo-HSCT to relapse (interaction p < 0.05). Furthermore, the preemptive treatment for molecular relapse/minimal residual disease positivity resulted in much better outcomes than that for hematological relapse, both in terms of CR and 2-year OS (interaction p < 0.001).

CONCLUSION

The regimen of azacitidine and DLI could safely improve the outcomes of relapsed AML/MDS after allo-HSCT, especially in those with signs of early relapse. The administration of targeted medicines in azacitidine-based therapies may further improve the outcomes of relapsed AML/MDS.

摘要

背景

对于异基因造血干细胞移植(allo-HSCT)后复发的急性髓系白血病(AML)和骨髓增生异常综合征(MDS)患者,阿扎胞苷联合供者淋巴细胞输注(DLI)是进行抢先治疗或挽救治疗的可行选择。然而,其疗效缺乏全面分析,本研究旨在填补这一空白。

方法

我们在PUBMED、EMBASE和Cochrane对照试验中央注册库中检索潜在研究。分析了13项涉及811例患者的研究。采用逆方差法计算合并比例和95%置信区间(CI)。进行亚组分析以探索异质性来源。

结果

合并完全缓解+部分缓解(CR+PR)率、CR率和2年总生存率(OS)分别为30%(95%CI:22%-39%)、21%(95%CI:16%-28%)和31%(95%CI:27%-35%)。合并急性移植物抗宿主病(GvHD)和慢性GvHD率分别为15%(95%CI:9%-23%)和14%(95%CI:8%-23%)。不良细胞遗传学和复发时较高比例的骨髓(BM)原始细胞与较差的CR+PR和CR相关(交互作用p<0.05)。复发时BM原始细胞比例较低或allo-HSCT至复发时间较长的患者2年OS较高(交互作用p<0.05)。此外,无论是CR还是2年OS,针对分子复发/微小残留病阳性的抢先治疗均比血液学复发的治疗效果好得多(交互作用p<0.001)。

结论

阿扎胞苷和DLI方案可安全改善allo-HSCT后复发的AML/MDS的预后,尤其是那些有早期复发迹象的患者。在基于阿扎胞苷的治疗中使用靶向药物可能会进一步改善复发的AML/MDS的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f4e/9389555/f5f6593b501d/fonc-12-949534-g001.jpg

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