Extramedullary relapse and discordant CD19 expression between bone marrow and extramedullary sites in relapsed acute lymphoblastic leukemia after blinatumomab treatment
Extramedullary relapse and discordant CD19 expression between bone marrow and extramedullary sites in relapsed acute lymphoblastic leukemia after blinatumomab treatment
复制标题
DOI：
10.1016/j.currproblcancer.2018.04.006
复制
发表时间：
2019-06-01
影响因子：
2.6
通讯作者：
Anagnostopoulos, Achilles
中科院分区：
文献类型：
--
作者：
Demosthenous, Christos;Lalayanni, Chrysavgi;Anagnostopoulos, Achilles
Blinatumomab 是一种靶向 CD19 的双特异性 T 细胞接合抗体构建体，已被证明可以改善复发性和/或难治性 B 细胞急性淋巴细胞白血病患者的预后。与化疗相比，blinatumomab 治疗显示出显着的生存获益，支持其用作同种异体造血干细胞移植的桥梁疗法。不幸的是，在最初缓解后，大约 50% 的缓解患者最终复发。在失败时，大多数患者具有 CD19 阳性原始细胞，但据报道，CD19 阴性复发的数量令人担忧。在本文报告的数据中，我们介绍了一名 42 岁原发性难治性 B 细胞急性淋巴细胞白血病患者的有趣病例，该患者在使用 blinatumomab 单药一个周期后实现了完全形态学缓解。值得注意的是，在没有髓外疾病史的情况下，骨髓中的反应与 CD19 阳性髓外复发的出现同时发生，包括活检证实的先前穿刺血液和骨髓样本的部位，以及实质器官（例如乳腺和肺）。在 blinatumomab 的第二个周期中，出现了 CD19 阴性形态学复发。 CD19 的丢失是一个短暂的事件，因为化疗后白血病细胞部分恢复了 CD19。这项研究说明了暴露于双特异性 T 细胞接合抗体（例如 blinatumomab）后，复发难治性急性淋巴细胞白血病并发髓外疾病的挑战性情况。医生应对髓外白血病的演变保持高度怀疑。这种对博纳吐单抗的耐药和/或复发模式类似于同种异体移植后的移植物抗白血病效应（在血液和骨髓中比在其他组织中更强）。对 blinatumomab 的耐药机制尚不清楚。对于难治性患者和髓外疾病高风险患者的联合治疗可能需要未来的评估。 (C) 2018 Elsevier Inc. 保留所有权利。
Blinatumomab, a bispecific T-cell engager antibody construct targeting CD19, has been shown to improve the outcome in patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia. Treatment with blinatumomab demonstrated significant survival benefit over chemotherapy, supporting its use as a bridge therapy to allogeneic hematopoietic stem cell transplantation. Unfortunately, following initial response, approximately 50% of responding patients eventually relapse. At the time of failure, the majority of patients have CD19-positive blasts, yet a concerning number of CD19-negative relapses has been reported. In the data reported herein, we present an interesting case of a 42-year old patient with primary refractory B-cell acute lymphoblastic leukemia who achieved complete morphologic remission after one cycle of blinatumomab as a single agent. Notably, and in the absence of extramedullary disease history, the response in marrow coincided with the emergence of CD19-positive extramedullary relapse including sites of previous punctures for blood and bone marrow samples, as confirmed by biopsy, as well as parenchymal organs (eg breast and lung). During the second cycle of blinatumomab, a CD19-negative morphological relapse emerged. The loss of CD19 was a transient event, as leukemic cells partially regained it after chemotherapy. This study illustrates a challenging situation of relapsed and refractory acute lymphoblastic leukemia complicated with extramedullary disease after exposure to a bispecific T-cell engager antibody, such as blinatumomab. Physicians should maintain a high level of suspicion for the evolution of extramedullary leukemia. This pattern of resistance and/or relapse to blinatumomab resembles the graft-versus-leukemia effect after allogeneic transplantation (stronger in blood and marrow than in other tissues). Mechanisms of resistance to blinatumomab are not yet clear. Combination treatments for refractory patients and those at high risk for exramedullary disease may warrant future assessment. (C) 2018 Elsevier Inc. All rights reserved.