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达雷木单抗治疗异基因移植后的红细胞植入延迟
Daratumumab for Delayed Red-Cell Engraftment after Allogeneic Transplantation


Claudia I. Chapuy ... 肿瘤 • 2018.11.08
相关阅读
• 异基因干细胞移植后红细胞再生障碍的逆转

概要


达雷木单抗(daratumumab)是一种靶向CD38的人IgG1κ单克隆抗体,用于治疗多发性骨髓瘤。我们下面描述一个病例,在这个病例中,使用达雷木单抗成功治疗了ABO血型不合异基因干细胞移植后发生的难治性纯红细胞再生障碍。患者是一名患骨髓增生异常综合征的72岁男性,他接受了主要ABO血型不合(供者血型为A型,受者血型为O型)且HLA匹配的无血缘供者的移植。患者有持续的循环抗A抗体,并且在移植后200日,红细胞未恢复。标准治疗无效。在开始达雷木单抗治疗后1周内,患者不再需要输血。

异基因干细胞移植是恶性血液病(包括骨髓增生异常综合征)患者的一个治愈方案。在25%~50%的移植中,HLA匹配的异基因干细胞供者与受者有一定程度的ABO血型不合,因为HLA和ABO基因是独立遗传的1

ABO血型不合被分类为主要ABO血型不合(由针对供者红细胞的受者抗体引起)或次要ABO血型不合(由针对受者红细胞的供者抗体的被动转移引起)。由针对供者红细胞的持续性受者抗体引起的ABO血型不合所导致的后果是红细胞恢复可能延迟数月2。受者的骨髓特征性地缺乏红系前体细胞(纯红细胞再生障碍)。移植后纯红细胞再生障碍的发生率为6%~30% 3,4,并因预处理方案不同而异。在接受A血型供者移植的O血型受者中,纯红细胞再生障碍的风险增加5,6。这些患者通常无法检测到网织红细胞,仍然依赖红细胞输血,并且有输血相关的铁超负荷风险。

移植后纯红细胞再生障碍的最佳治疗仍不清楚。目前的疗法包括免疫抑制剂逐渐减量、给予红细胞生成刺激剂、给予糖皮质激素、血浆交换、给予利妥昔单抗和输入供者淋巴细胞4,7-10

达雷木单抗是针对CD38的人IgG1κ单克隆抗体,CD38在浆细胞上有高水平表达。达雷木单抗的作用机制包括补体依赖性细胞毒性、抗体依赖性细胞毒性、抗体依赖性细胞吞噬作用和凋亡信号传导11。在一个病例中,成功使用达雷木单抗治疗移植后自身免疫性溶血性贫血,该患者对包括利妥昔单抗在内的既往多种治疗无应答12。我们描述了使用达雷木单抗治疗1名输血依赖患者,该患者对移植后纯红细胞再生障碍的其他治疗方案无应答。我们假设用达雷木单抗直接靶向CD20阴性但CD38阳性的浆细胞会减少红细胞抗体产生,并使得红细胞恢复。





作者信息

Claudia I. Chapuy, M.D., Richard M. Kaufman, M.D., Edwin P. Alyea, M.D., and Jean M. Connors, M.D.
From the Dana–Farber Cancer Institute at St. Elizabeth’s Medical Center (C.I.C.), Blood Bank, Department of Pathology (R.M.K.), and the Division of Hematology (J.M.C.), Brigham and Women’s Hospital, and the Department of Medical Oncology, Dana–Farber Cancer Institute (E.P.A.) — all in Boston; and the Department of Hematology and Oncology, University Medical Center, Göttingen, Germany (C.I.C.). Address reprint requests to Dr. Connors at the Division of Hematology, 75 Francis St., Brigham and Women’s Hospital, Boston, MA 02115, or at jconnors@bwh.harvard.edu.

 

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