Hashino S, Imamura M, Tanaka J, Kobayashi S, Musashi M, Kasai M, Asaka M
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Ann Hematol. 1996 May;72(5):337-9. doi: 10.1007/s002770050183.
A cytogenetically normal man with severe aplastic anemia was treated with granulocyte colonystimulating factor (G-CSF), erythropoietin (EPO), cyclosporin A, anti-thymocyte globulin, and interleukin-6 (IL-6), which resulted in a gradual improvement in his neutrophil count and hemoglobin level. After 2 years of the therapy, monosomy 7 was detected during cytogenetic analysis of his bone marrow, which evolved during a period of 5 months into acute myeloblastic leukemia. An in vitro proliferation assay of cytokine responses showed that leukemic blasts were sensitive only to G-CSF, and not to EPO or IL-6. Although allogeneic bone marrow transplantation from an HLA-matched unrelated donor was carried out in the non-remission stage, the patient died of systemic fungal infection on day 25, without any evidence of hematological engraftment. As long-term use of cytokines and immunomo-suppressants in patients with severe aplastic anemia may induce or hasten the onset of a malignant transformation, careful attention must be paid to clonal evolution. Due to the poor prognosis of secondary myelodysplasia and leukemia, allogeneic bone marrow transplantation for such patients must be carried out early in the course of the disease.
一名细胞遗传学正常的重度再生障碍性贫血男性患者接受了粒细胞集落刺激因子（G-CSF）、促红细胞生成素（EPO）、环孢素A、抗胸腺细胞球蛋白和白细胞介素-6（IL-6）治疗，其中性粒细胞计数和血红蛋白水平逐渐改善。治疗2年后，在对其骨髓进行细胞遗传学分析时检测到7号染色体单体，该情况在5个月内演变为急性髓细胞白血病。细胞因子反应的体外增殖试验表明，白血病原始细胞仅对G-CSF敏感，而对EPO或IL-6不敏感。尽管在未缓解阶段进行了来自人类白细胞抗原（HLA）匹配的无关供体的异基因骨髓移植，但患者在第25天死于全身性真菌感染，没有任何血液学植入的迹象。由于在重度再生障碍性贫血患者中长期使用细胞因子和免疫抑制剂可能会诱导或加速恶性转化的发生，因此必须密切关注克隆演变。鉴于继发性骨髓增生异常和白血病的预后较差，对此类患者的异基因骨髓移植必须在疾病进程早期进行。
