title: Pure red cell aplasia developing into myeloproliferation with myelodysplasia and subsequent leukemia after cyclosporin A therapy.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Fukui Medical University, Matsuoka, Japan. tyamauch@fmsrsa.fukui-med.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Shirasaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuwata
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Shin
authors.initials: S
authors.lastname: Imamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsutani
authors.forename: Takanori
authors.initials: T
authors.lastname: Ueda
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002898:Chromosomes, Human, Pair 8; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D017809:Fatal Outcome; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000139:chemically induced / Q000473:pathology; D012010:Red-Cell Aplasia, Pure / Q000188:drug therapy / Q000473:pathology*; D014314:Trisomy
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine