Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2022 Feb 2;13:810284. doi: 10.3389/fimmu.2022.810284. eCollection 2022.
Acute myeloid leukemia (AML) patients who develop hematological relapse (HR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally have dismal clinical outcomes. Measurable residual disease (MRD)-directed preemptive interventions are effective approaches to prevent disease progression and improve prognosis for molecular relapsed patients with warning signs of impending HR. In this situation, boosting the graft-vs-leukemia (GVL) effect with immune checkpoint inhibitors (ICIs) might be a promising prevention strategy, despite the potential for causing severe graft-vs-host disease (GVHD). In the present study, we reported for the first time an AML patient with who underwent preemptive treatment with the combined application of tislelizumab (an anti-PD-1 antibody) and azacitidine to avoid HR following allo-HSCT. On day +81, molecular relapse with MRD depicted by -positivity as well as mixed donor chimerism occurred in the patient. On day +95, with no signs of GVHD and an excellent eastern cooperative oncology group performance status (ECOG PS), the patient thus was administered with 100 mg of tislelizumab on day 1 and 100 mg of azacitidine on days 1-7. After the combination therapy, complete remission was successfully achieved with significant improvement in hematologic response, and the MRD marker turned negative, along with a complete donor chimerism in bone marrow. Meanwhile, the patient experienced moderate GVHD and immune-related adverse events (irAEs), successively involving the lung, liver, lower digestive tract and urinary system, which were well controlled by immunosuppressive therapies. As far as we know, this case is the first one to report the use of tislelizumab in combination with azacitidine to prevent post-transplant relapse in AML. In summary, the application of ICIs in MRD positive patients might be an attractive strategy for immune modulation in the future to reduce the incidence of HR in the post-transplant setting, but safer clinical application schedules need to be explored.
异基因造血干细胞移植（allo-HSCT）后发生血液学复发（HR）的急性髓系白血病（AML）患者通常临床结局较差。基于微小残留病灶（MRD）的前瞻性干预是防止疾病进展和改善具有 HR 潜在预警信号的分子复发患者预后的有效方法。在这种情况下，使用免疫检查点抑制剂（ICIs）增强移植物抗白血病（GVL）效应可能是一种有前途的预防策略，尽管存在导致严重移植物抗宿主病（GVHD）的风险。本研究首次报道了 1 例 AML 患者，该患者在 allo-HSCT 后接受了 tislelizumab（一种抗 PD-1 抗体）联合阿扎胞苷的抢先治疗，以避免 HR。在第+81 天，患者出现了由 -阳性表示的分子复发和混合供者嵌合。在第+95 天，患者无 GVHD 迹象且东部肿瘤协作组体能状态（ECOG PS）良好，因此在第 1 天给予 100 mg tislelizumab，第 1-7 天给予 100 mg 阿扎胞苷。联合治疗后，完全缓解成功实现，血液学反应显著改善，MRD 标志物 转为阴性，骨髓中完全供者嵌合。同时，患者出现中度 GVHD 和免疫相关不良事件（irAEs），先后累及肺、肝、下消化道和泌尿系统，通过免疫抑制治疗得到良好控制。据我们所知，这是首例报告 tislelizumab 联合阿扎胞苷用于预防 AML 移植后复发的病例。总之，ICI 在 MRD 阳性患者中的应用可能是未来免疫调节的一种有吸引力的策略，以降低移植后 HR 的发生率，但需要探索更安全的临床应用方案。
