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单倍体造血干细胞移植后HLA缺失复发的博纳吐单抗治疗

Blinatumomab for HLA loss relapse after haploidentical hematopoietic stem cell transplantation.

作者信息

Wu Hengwei, Cai Zhen, Shi Jimin, Luo Yi, Huang He, Zhao Yanmin

机构信息

Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, Zhejiang Province, China.

Institute of Hematology, Zhejiang University Hangzhou, Zhejiang Province, China.

出版信息

Am J Cancer Res. 2021 Jun 15;11(6):3111-3122. eCollection 2021.

Abstract

Loss of patient-specific HLA after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is considered as a relapse mechanism for lacking the incompatible molecule to elicit alloreactivity, which extensively diminishing graft-versus-leukemia (GVL) effects. Blinatumomab, as a CD3/CD19 bispecific antibody, can yield a profound response via redirecting T cells towards malignant lymphoblasts in B-cell acute lymphoblastic leukemia (B-ALL). We aimed to assess the feasibility of blinatumomab in treating patients with HLA loss relapse after haplo-HSCT. Four eligible patients undergoing HLA loss relapse after haplo-HSCT were enrolled in the study. Four patients achieved a complete remission/complete remission with partial he-matologic recovery (CR/CRh) with three minimal residual disease (MRD)-negative response within the first cycle of treatment. Three of the four met a primary endpoint with CR/CRh and MRD-negative response within 2 cycles of treatment. One patient developed new extramedullary sites of skin after the first cycle. Cytokine release syndrome was observed in one patient. Cytopenias, as well as elevated alanine aminotransferase and aspartate aminotransferase, were two common adverse effects during treatment. By redirecting lysis of CD19-positive lymphoblast who losing the incompatible HLA, blinatumomab is a potential strategy to eradicate malignant cells via restoring GVL effects. A randomized clinical trial assessing blinatumomab in patients with HLA loss relapse after HSCT is warranted.

摘要

单倍体相合造血干细胞移植(haplo-HSCT)后患者特异性人类白细胞抗原(HLA)的丢失被认为是一种复发机制,因为缺乏不相容分子来引发同种异体反应,这会广泛削弱移植物抗白血病(GVL)效应。博纳吐单抗作为一种CD3/CD19双特异性抗体,可通过将T细胞重定向至B细胞急性淋巴细胞白血病(B-ALL)中的恶性淋巴母细胞而产生显著反应。我们旨在评估博纳吐单抗治疗haplo-HSCT后HLA丢失复发患者的可行性。四名haplo-HSCT后发生HLA丢失复发的符合条件患者被纳入研究。四名患者在治疗的第一个周期内实现了完全缓解/伴有部分血液学恢复的完全缓解(CR/CRh),其中三名患者获得了微小残留病(MRD)阴性反应。四名患者中有三名在2个周期的治疗内达到了CR/CRh和MRD阴性反应的主要终点。一名患者在第一个周期后出现了新的皮肤髓外病变部位。一名患者观察到细胞因子释放综合征。血细胞减少以及丙氨酸转氨酶和天冬氨酸转氨酶升高是治疗期间的两种常见不良反应。通过重定向对丢失不相容HLA的CD19阳性淋巴母细胞的裂解,博纳吐单抗是一种通过恢复GVL效应来根除恶性细胞的潜在策略。有必要进行一项随机临床试验,评估博纳吐单抗在HSCT后HLA丢失复发患者中的疗效。

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