Hemato-Oncology Department, Medical School, University of Salerno, Italy.
Mini Rev Med Chem. 2011 Jun;11(6):536-43. doi: 10.2174/138955711795843329.
Acquired bone marrow failure syndromes (BMFS) are a heterogeneous group of hematological disorders characterized by impaired bone marrow function and subsequent cytopenia of one or more blood cell lineages [1,2]. The well-accepted pathogenic mechanism of the typical bone marrow failure - aplastic anemia (AA)- is a T cell mediated immune attack targeting the hematopoietic tissue [3]. This pathogenic mechanism is at least partially shared by other bone marrow failure syndromes, such as lineage-restricted aplasias and some myelodysplastic syndromes. Thus, for these disorders immunosuppression (IS) is the pivotal etiologic treatment. While the standard IS regimen include the heterologous anti-thymocyte globulin [4], here we review the recent data on the anti-CD52 monoclonal antibody alemtuzumab as a novel IS agent for marrow failures. Alemtuzumab led to objective responses in aplastic anemia patients in 3 recent prospective studies, with overall response rates ranging between 37% and 72%. Adverse events were irrelevant, ruling out even the concerns about the risk of infectious complications. Alemtuzumab was effective even for the treatment of lineage-restricted marrow failure, with very acceptable toxicity and excellent response rates (as high as 80%). More recently, even patients suffering from myelodysplastic syndromes showed a remarkable hematological response to alemtuzumab-based IS treatment. Thus, alemtuzumab is a novel IS agent representing an excellent alternative to ATG for all immune-mediated marrow failure syndromes. Even if the dose and the schedule may still require further refining, the available data support the need of large prospective trials comparing alemtuzumab to current standard IS regimens.
获得性骨髓衰竭综合征（BMFS）是一组异质性血液系统疾病，其特征为骨髓功能受损，随后出现一种或多种血细胞谱系的细胞减少症[1,2]。典型骨髓衰竭-再生障碍性贫血（AA）的公认发病机制是 T 细胞介导的针对造血组织的免疫攻击[3]。这种发病机制至少部分存在于其他骨髓衰竭综合征中，如谱系受限的再生障碍和一些骨髓增生异常综合征。因此，对于这些疾病，免疫抑制（IS）是关键的病因治疗。虽然标准的 IS 方案包括异源抗胸腺细胞球蛋白[4]，但在这里我们回顾了最近关于抗 CD52 单克隆抗体阿仑单抗作为骨髓衰竭新的 IS 药物的研究数据。阿仑单抗在 3 项最近的前瞻性研究中导致再生障碍性贫血患者出现客观反应，总反应率在 37%至 72%之间。不良事件无关紧要，甚至排除了对感染并发症风险的担忧。阿仑单抗甚至对谱系受限的骨髓衰竭的治疗有效，毒性可接受，反应率非常高（高达 80%）。最近，即使是患有骨髓增生异常综合征的患者，也对基于阿仑单抗的 IS 治疗表现出显著的血液学反应。因此，阿仑单抗是一种新型 IS 药物，是所有免疫介导的骨髓衰竭综合征中抗胸腺细胞球蛋白的理想替代药物。即使剂量和方案可能仍需要进一步优化，现有数据支持需要进行大规模前瞻性试验，比较阿仑单抗与当前的标准 IS 方案。
