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初诊急性髓系白血病患者血小板输注无效的临床和免疫学特征。

Clinical and immunological features of platelet transfusion refractoriness in young patients with de novo acute myeloid leukemia.

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Lishui City People's Hospital, Zhejiang, China.

出版信息

Cancer Med. 2020 Jul;9(14):4941-4948. doi: 10.1002/cam4.3140. Epub 2020 May 18.

Abstract

Platelet transfusion is important in the prevention and treatment of bleeding in patients with acute myeloid leukemia (AML) after receiving intensive chemotherapy. However, platelet transfusion refractoriness (PTR) is an intractable clinical issue occurred in these patients. And its clinical and immunological features remain largely unknown. The potential causes and clinical features of PTR were retrospectively analyzed in 560 patients who were diagnosed as de novo AML in Tongji Hospital from June 2012 through June 2018. A high-throughput antibody screening for the detection of human leukocyte antigen (HLA) and its serotypes was performed in 133 newly diagnosed AML patients. PTR occurred in 11.8% of the de novo AML patients. The median age for patients with PTR was 46 years (range, 15-70). It frequently manifested in female patients and in patients with splenomegaly, M4 subtype, c-Kit gene mutation, and rearrangements of RUNX1-RUNX1T1 or CBFB-MYH11, commonly referred to as core binding factor AML (CBF-AML). Notably, CBF-AML was independently associated with the occurrence of PTR. PTR predominantly developed in patients who had CBF-AML (P < .001) and in patients who further had better minimal residual disease (MRD) reduction (≥3-log) before the second consolidation chemotherapy (P = .007). HLA-I antibodies were detected in the serum of 9.0% of AML patients and markedly enriched in patients with PTR (P < .001) and in patients with CBF-AML (P = .018). HLA-B was the most frequently identified serum epitope in PTR patients. Patients with CBF-AML had higher tendency to develop HLA-I antibodies and PTR, which depicted novel features of PTR in AML and might provide insights into its efficient managements.

摘要

血小板输注在接受强化化疗的急性髓系白血病(AML)患者预防和治疗出血中很重要。然而,血小板输注无效(PTR)是这些患者中一个棘手的临床问题。其临床和免疫学特征在很大程度上仍不清楚。我们回顾性分析了 2012 年 6 月至 2018 年 6 月在同济医院诊断为初发 AML 的 560 例患者的潜在原因和 PTR 的临床特征。对 133 例新诊断的 AML 患者进行了高通量抗体筛选,以检测人类白细胞抗原(HLA)及其血清型。初发 AML 患者中 PTR 的发生率为 11.8%。PTR 患者的中位年龄为 46 岁(范围 15-70 岁)。PTR 常发生于女性患者和脾肿大、M4 亚型、c-Kit 基因突变、RUNX1-RUNX1T1 或 CBFB-MYH11 重排,通常称为核心结合因子 AML(CBF-AML)患者。值得注意的是,CBF-AML 与 PTR 的发生独立相关。PTR 主要发生在 CBF-AML 患者(P <.001)和进一步在第二次巩固化疗前具有更好的微小残留病(MRD)减少(≥3-log)的患者中(P =.007)。AML 患者的血清中检测到 9.0%的 HLA-I 抗体,且在 PTR 患者(P <.001)和 CBF-AML 患者(P =.018)中明显富集。HLA-B 是 PTR 患者中最常鉴定的血清表位。CBF-AML 患者更倾向于产生 HLA-I 抗体和 PTR,这描绘了 AML 中 PTR 的新特征,可能为其有效管理提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d026/7367618/bf07c1b48c86/CAM4-9-4941-g001.jpg

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