International Journal of Hematology

, Volume 75, Issue 5, pp 514–518 | Cite as

Pure Red Cell Aplasia Developing into Myeloproliferation with Myelodysplasia and Subsequent Leukemia after Cyclosporin A Therapy

  • Takahiro Yamauchi
  • Haruhisa Shirasaki
  • Atsushi Kuwata
  • Taro Yamashita
  • Shin Imamura
  • Hiroshi Tsutani
  • Takanori Ueda
Case Report


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/μL and 1,000,000/μL, 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-β-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.

Key words

Pure red cell aplasia Myelodysplastic syndrome Acute leukemia Cyclosporin A Autoimmune reaction 


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  1. 1.
    Dessypris EN.The biology of pure red cell aplasia.Semin Hematol. 1991;28:275–284.PubMedGoogle Scholar
  2. 2.
    Fisch P, Handgretinger R, Schaefer H-E. Pure red cell aplasia.Br J Haematol. 2000;111:1010–1022.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes.Br J Haematol. 1982;51: 189–199.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Craig A, Geary CG, Love EM, Liu-Yin J. Red cell hypoplasia, thrombocytosis, and leucocytosis: myelodysplastic and proliferative syndrome.J Clin Pathol. 1988;41:1168–1170.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Cook MK. Red cell hypoplasia associated with myeloproliferative and myelodysplastic syndrome.J Clin Pathol. 1988;42:890–891.CrossRefGoogle Scholar
  6. 6.
    Bolton-Maggs PHB, Galloway MJ, Rhodes EG. Pure red cell aplasia heralding chronic myelomonocytic leukaemia.Clin Lab Haematol. 1989;11:61–65.CrossRefPubMedGoogle Scholar
  7. 7.
    Lopez-Guillermo A, Cervantes F, Sacanella E, Florensa L, Rozman C. Pure red cell aplasia associated with chronic myelomonocytic leukaemia.Clin Lab Haematol. 1989;11:410–411.CrossRefPubMedGoogle Scholar
  8. 8.
    Williamson PJ, Oscier DG, Bell AJ, Hamblin TJ. Red cell aplasia in myelodysplastic syndrome.J Clin Pathol. 1991;44:431–432.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Garcia-Suarez J, Pascual T, Munoz MA, Herrero B, Pardo A. Myelodysplastic syndrome with erythroid hypoplasia/aplasia: a case report and review of the literature.Am J Hematol. 1998;58: 319–325.CrossRefPubMedGoogle Scholar
  10. 10.
    Yokohama A, Murata N, Shimano S, et al. Myelodysplastic syndrome accompanied by i(17) (q10) anomaly following pure red cell aplasia and transient myeloproliferative stage.Jpn J Clin Hematol.1999;40:34–39.Google Scholar
  11. 11.
    Hashino S, Imamura M, Tanaka J, et al. Transformation of severe aplastic anemia into acute myeloblastic leukemia with monosomy 7.Ann Hematol. 1996;72:337–339.CrossRefPubMedGoogle Scholar
  12. 12.
    Jonasova A, Neuwirtova R, Cermak J, et al. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anemias without hypoplastic bone marrow.Br J Haematol. 1998;100:304–309.CrossRefPubMedGoogle Scholar
  13. 13.
    Tichelli A, Gratwohl A, Wuersch A, Nissen C, Speck B. Antilymphocyte globulin for myelodysplastic syndrome?Br J Haematol.1988;68:139–140.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Miescher PA, Favre H, Beris P. Autoimmune myelodysplasias.Semin Hematol. 1991;28:322–330.PubMedGoogle Scholar
  15. 15.
    Young NS. The problem of clonality in aplastic anemia: Dr Dameshek’s riddle, restarted.Blood. 1992;79:1385–1392.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Enright H, Jacob HS, Vercellotti G, Howe R, Belzer M, Miller W. Paraneoplastic autoimmune phenomena in patients with myelo-dysplastic syndromes: response to immunosuppressive therapy.Br J Haematol. 1995;91:403–408.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Biesma DH, van den Tweel JG, Verdonck LF. Immunosuppressive therapy for hypoplastic myelodysplastic syndrome.Cancer. 1997; 79:1548–1551.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Takanashi M, Kadono Y, Tabata Y, Hibi S. Successful immunosup-pressive therapy for a patient with hypoplastic myelodysplastic syndrome.Jpn J Clin Hematol. 1999;40:1093–1099.Google Scholar
  19. 19.
    Catalano L, Selleri C, Califano C, et al. Prolonged response to cyclosporin-A in hypoplastic refractory anemia and correlation with in vitro studies.Haematologica. 2000;85:133–138.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Nemoto Y, Tsutani H, Imamura S, et al. Successful treatment of acquired myelofibrosis with pure red cell aplasia by cyclosporine.Br J Haematol. 1999;104:422–424.CrossRefPubMedGoogle Scholar
  21. 21.
    Weinstein IM. Idiopathic myelofibrosis: historical review, diagnosis and management.Blood Rev. 1991;5:98–104.CrossRefPubMedGoogle Scholar
  22. 22.
    Garcia-Isidoro M, Tabernero MD, Najera ML, et al. Association between trisomy 8 and the immunophenotype of blast cells from acute leukemias secondary to a myelodysplastic syndrome or chronic myeloproliferative disorders.Ann Hematol. 1997;74: 209–214.CrossRefPubMedGoogle Scholar
  23. 23.
    Fagioli F, Cuneo A, Bardi A, et al. Heterogeneity of lineage involvement by trisomy 8 in myelodysplastic syndrome: a multipa-rameter analysis combining conventional cytogenetics, DNA in situ hybridization, and bone marrow culture studies.Cancer Genet Cytogenet. 1995;82:116–122.CrossRefPubMedGoogle Scholar
  24. 24.
    Fugazza G, Bruzzone R, Dejana AM, et al. Cytogenetic clonality in chronic myelomonocytic leukemia studied with fluorescence in situ hybridization.Leukemia. 1995;9:109–114.PubMedGoogle Scholar
  25. 25.
    Elis A, Amiel A, Manor Y,Tangi I, Fejgin M, Lishner M.The detec- tion of trisomies 8 and 9 in patients with essential thrombocytosis by fluorescence in situ hybridization.Cancer Genet Cytogenet. 1996;92:14–17.CrossRefPubMedGoogle Scholar
  26. 26.
    Mhawech P, Saleem A. Myelodysplastic syndrome: review of the cytogenetic and molecular data.Crit Rev Oncol Hematol. 2001;40: 229–238.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  • Takahiro Yamauchi
    • 1
  • Haruhisa Shirasaki
    • 1
  • Atsushi Kuwata
    • 1
  • Taro Yamashita
    • 1
  • Shin Imamura
    • 1
  • Hiroshi Tsutani
    • 1
  • Takanori Ueda
    • 1
  1. 1.First Department of Internal MedicineFukui Medical UniversityMatsuoka, FukuiJapan

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