Yamauchi Takahiro, Shirasaki Haruhisa, Kuwata Atsushi, Yamashita Taro, Imamura Shin, Tsutani Hiroshi, Ueda Takanori
First Department of Internal Medicine, Fukui Medical University, Matsuoka, Japan.
Int J Hematol. 2002 Jun;75(5):514-8. doi: 10.1007/BF02982116.
We describe a very rare case of a patient who presented with red cell aplasia that later developed into myeloproliferation with myelodysplasia and eventually leukemia. A 63-year-old man presented with anemia and reticulocytopenia in May 1997. A bone marrow examination revealed erythroid aplasia with normal production of myeloid cells and megakaryocytes with a normal karyotype. After the diagnosis of pure red cell aplasia was made, the patient was treated with prednisolone and then with cyclosporin A (CyA). Two weeks after the initiation of CyA treatment, the peripheral reticulocyte count began to increase with a regrowth of erythroid cells in the bone marrow. Meanwhile, the peripheral white blood cell and platelet counts also increased to more than 10,000/microL and 1,000,000/microL, respectively. Examination of a bone marrow aspirate in December 1997 revealed myelodysplastic changes with trisomy 8. Despite the discontinuation of CyA and the administration of 1-beta-D-arabinofuranosylcytosine stearyl monophosphate, leukemia developed in August 1998. In September 1998, the patient died of sepsis during a neutropenic period that followed remission-induction therapy. In the mechanism of pathogenesis, CyA may induce upon pure red cell aplasia a secondary myeloproliferative disorder with myelodysplasia and leukemia. An alternative possibility is that CyA reduces autoimmune-mediated suppression of the underlying stem cell disorder and that the result of this reduction is the manifestation of myeloproliferation and leukemia.
我们描述了一例非常罕见的病例,该患者最初表现为单纯红细胞再生障碍,随后发展为骨髓增殖伴骨髓发育异常,最终发展为白血病。一名63岁男性于1997年5月出现贫血和网织红细胞减少。骨髓检查显示红系再生障碍,髓系细胞和巨核细胞生成正常,核型正常。在诊断为纯红细胞再生障碍后,患者先接受泼尼松龙治疗,后接受环孢素A(CyA)治疗。CyA治疗开始两周后,外周血网织红细胞计数开始增加,骨髓中红系细胞再生。与此同时,外周血白细胞和血小板计数也分别增加至超过10,000/微升和1,000,000/微升。1997年12月的骨髓穿刺检查显示有8号染色体三体的骨髓发育异常改变。尽管停用了CyA并给予了1-β-D-阿拉伯呋喃糖基胞嘧啶硬脂酸单磷酸酯,但患者仍于1998年8月发展为白血病。1998年9月,患者在诱导缓解治疗后的中性粒细胞减少期死于败血症。在发病机制方面,CyA可能在纯红细胞再生障碍的基础上诱发继发性骨髓增殖性疾病伴骨髓发育异常和白血病。另一种可能性是,CyA减轻了自身免疫介导的对潜在干细胞疾病 的抑制作用,而这种减轻的结果是骨髓增殖和白血病的表现。