Larsen Mathilde Skaarup, Hasselbalch Hans Carl
Medicinsk Afdeling, Haematologisk-Onkologisk Afsnit, Amtssygehuset Roskilde, Køgevej 7-13, DK-4000 Roskilde.
Ugeskr Laeger. 2003 Jun 23;165(26):2654-7.
The myelodysplastic syndrome (MDS) is featured by cytopenia in one or more cell lineages. Until recently the only possible treatment was supportive care with transfusions and antibiotics, but new options have now become available. In this article the results of immunosuppressive treatment are described and discussed.
We present seven patients who were treated with antithymocyte globulin (ATG) and cyclosporine. Previous series of patients with MDS treated with ATG are summarized.
Two of the seven patients treated with ATG and cyclosporine achieved a complete response, one had a partial response and one had a minor response.
In MDS an acquired insult to the hemopoietic stem cell leads to impaired differentiation and myelodysplasia. A model of MDS pathophysiology suggests that transformation of normal stem cells induces an autoimmune T cell response with the bone marrow as the target organ. This autoimmune attack results in chronic overproduction of pro-apoptotic cytokines, especially TNF-alpha. This may contribute to a dysplastic morphology and increased apoptosis in the marrow. It is suggested that the mechanism of action of ATG in MDS may involve elimination of CD8+ lymphocyte mediated suppression of granulocyte/monocyte progenitor cells.
骨髓增生异常综合征(MDS)的特征是一个或多个细胞系血细胞减少。直到最近,唯一可行的治疗方法是通过输血和使用抗生素进行支持性护理,但现在已有新的治疗选择。本文描述并讨论了免疫抑制治疗的结果。
我们介绍了7例接受抗胸腺细胞球蛋白(ATG)和环孢素治疗的患者。总结了先前接受ATG治疗的MDS患者系列。
7例接受ATG和环孢素治疗的患者中,2例获得完全缓解,1例部分缓解,1例轻微缓解。
在MDS中,造血干细胞受到后天损伤导致分化受损和骨髓发育异常。MDS病理生理学模型表明,正常干细胞的转化会引发以骨髓为靶器官的自身免疫性T细胞反应。这种自身免疫攻击导致促凋亡细胞因子,尤其是肿瘤坏死因子-α的慢性过度产生。这可能导致骨髓发育异常形态和凋亡增加。有人认为,ATG在MDS中的作用机制可能涉及消除CD8 +淋巴细胞介导的对粒细胞/单核细胞祖细胞的抑制。