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International Journal of Hematology

, Volume 79, Issue 1, pp 22–30 | Cite as

Diamond-Blackfan Anemia in Japan: Clinical Outcomes of Prednisolone Therapy and Hematopoietic Stem Cell Transplantation

  • Shouichi Ohga
  • Hideo Mugishima
  • Akira Ohara
  • Seiji Kojima
  • Kohji Fujisawa
  • Keiko Yagi
  • Masamune Higashigawa
  • Ichiro Tsukimoto
  • for the Aplastic Anemia Committee of the Japanese Society of Pediatric Hematology
Progress in hematology

Abstract

The epidemiology and treatment outcomes for Diamond-Blackfan anemia (DBA) were surveyed in a cohort of 54 children (M/F = 26:28) registered in Japan from 1988 to 1998. The annual incidence was 4.02 cases per million births, the median age at diagnosis was 60 days, and 59% of the cases presented by 3 months of age.Three patients had a familial occurrence. All patients received prednisolone (PSL), and cyclosporin A (CsA) was added to the therapy in 17 patients. Forty-seven patients received transfusions, and 13 underwent hematopoietic stem cell transplantation (HSCT).The cumulative probabilities of a medicationfree or a transfusion-free state prior to HSCT were 36% and 69%, respectively, at more than 5 years after diagnosis. Thirteen patients were weaned from PSL therapy without HSCT, and CsA was not associated with weaning from therapy. Transfusion and medication were stopped at 249 days and 933 days after diagnosis in 34 and 13 patients, respectively, who achieved a state of independence. No initial findings predicted the treatment dependence. More than 20% of patients experienced sustained hemosiderosis and/or adverse effects of PSL. The ages and reticulocyte counts at diagnosis of the patients who underwent HSCT were lower than in the patients who did not. HSCT led to the highest success (85%) of all previous reports, even though 5 alternative donors were included in our study. Two cord blood transplants from unrelated donors failed. These findings suggest the need for developing an integral treatment strategy including selective HSCT for refractory DBA.

Key words

Diamond-Blackfan anemia Bone marrow transplantation Cord blood transplantation Hematopoietic stem cell transplantation Cyclosporin A Prednisolone 

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References

  1. 1.
    Freedman MH. Diamond-Blackfan anaemia.Baillieres Best Pract Res Clin Haematol. 2000;13:391–406.CrossRefPubMedGoogle Scholar
  2. 2.
    Willig TN, Gazda H, Sieff CA. Diamond-Blackfan anemia.Curr Opin Hematol. 2000;7:85–94.CrossRefPubMedGoogle Scholar
  3. 3.
    Da Costa L, Willig TN, Fixler J, Mohandas N, Tchernia G. Diamond-Blackfan anemia.Curr Opin Pediatr. 2001;13:10–15.CrossRefGoogle Scholar
  4. 4.
    Halperin DS, Freedman MH. Diamond-Blackfan anemia: etiology, pathophysiology, and treatment.Am J Pediatr Hematol Oncol. 1989;11:380–394.PubMedGoogle Scholar
  5. 5.
    Krijanovski OI, Sieff CA. Diamond-Blackfan anemia.Hematol Oncol Clin North Am. 1997;11:1061–1077.CrossRefPubMedGoogle Scholar
  6. 6.
    Nomura A, Ohga S, Asaka Y, et al.Pneumocystis carinii pneumonia in Diamond-Blackfan anemia: the necessity of chemoprophylaxis for young infant.Int J Pediatr Hematol Oncol. 2000;7:7–11.Google Scholar
  7. 7.
    Huh WW, Gill J, Sheth S, Buchanan GR.Pneumocystis carinii pneumonia in patients with Diamond-Blackfan anemia receiving high- dose corticosteroids.J Pediatr Hematol Oncol. 2002;24:410–412.CrossRefPubMedGoogle Scholar
  8. 8.
    Alessandri AJ, Rogers PC, Wadsworth LD, Davis JH. Diamond- Blackfan anemia and cyclosporine therapy revisited.J Pediatr Hematol Oncol. 2000;22:176–179.CrossRefPubMedGoogle Scholar
  9. 9.
    Buchanan GR. Oral megadose methylprednisolone therapy for refractory Diamond-Blackfan anemia: International Diamond- Blackfan Anemia Study Group.J Pediatr Hematol Oncol. 2001;23:353–356.CrossRefPubMedGoogle Scholar
  10. 10.
    El-Beshlawy A, Ibrahim IY, Rizk S, Eid K. Study of 22 Egyptian patients with Diamond-Blackfan anemia, corticosteroids, and cyclosporin therapy results.Pediatrics. 2002;110:e44.CrossRefPubMedGoogle Scholar
  11. 11.
    Kawasaki H, Nakano T, Kohdera U, Kobayashi Y. The effect of thrombopoietin on erythroid progenitors in Diamond-Blackfan anemia.Int J Hematol. 2002;75:382–384.CrossRefPubMedGoogle Scholar
  12. 12.
    van Dijken PJ, Verwijs W. Diamond-Blackfan anemia and malignancy: a case report and a review of the literature.Cancer. 1995;76:517–520.CrossRefPubMedGoogle Scholar
  13. 13.
    Mugishima H, Gale RP, Rowlings PA,et al. Bone marrow transplantation for Diamond-Blackfan anemia.Bone Marrow Transplant. 1995;15:55–58.PubMedGoogle Scholar
  14. 14.
    Alter BP. Bone marrow transplant in Diamond-Blackfan anemia.Bone Marrow Transplant. 1998;21:965–966.CrossRefPubMedGoogle Scholar
  15. 15.
    Giri N, Kang E, Tisdale JF,et al. Clinical and laboratory evidence for a trilineage haematopoietic defect in patients with refractory Diamond-Blackfan anaemia.Br J Haematol. 2000;108:167–175.CrossRefPubMedGoogle Scholar
  16. 16.
    Draptchinskaia N, Gustavsson P, Andersson B, et al. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia.Nat Genet. 1999;21:169–175.CrossRefPubMedGoogle Scholar
  17. 17.
    Willig TN, Draptchinskaia N, Dianzani I, et al. Mutations in ribosomal protein S19 gene and Diamond Blackfan anemia: wide variations in phenotypic expression.Blood. 1999;94:4294–4306.PubMedGoogle Scholar
  18. 18.
    Hamagichi I, Ooka A, Brun A, Richter J, Dahl N, Karisson S. Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia.Blood. 2002;100:2724–2731.CrossRefGoogle Scholar
  19. 19.
    Gazda H, Lipton JM, Willig TN, et al. Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease.Blood. 2001;97:2145–2150.CrossRefPubMedGoogle Scholar
  20. 20.
    Ohga S, Kanaya Y, Maki H, et al. Epstein-Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond-Blackfan anemia.Bone Marrow Transplant. 2000;25:209–212.CrossRefPubMedGoogle Scholar
  21. 21.
    Alter BP. Childhood red cell aplasia.Am J Pediatr Hematol Oncol. 1980;2:121–139.Google Scholar
  22. 22.
    Ball SE, McGuckin CP, Jenkins G, Gordon-Smith EC. Diamond- Blackfan anaemia in the U.K.: analysis of 80 cases from a 20-year birth cohort.Br J Haematol. 1996;94:645–653.CrossRefPubMedGoogle Scholar
  23. 23.
    Janov AJ, Leong T, Nathan DG, Guinan EC. Diamond-Blackfan anemia: natural history and sequelae of treatment.Medicine (Baltimore). 1996;75:77–78.CrossRefGoogle Scholar
  24. 24.
    Ramenghi U, Campagnoli MF, Garelli E, et al. Diamond-Blackfan anemia: report of seven further mutations in the RPS19 gene and evidence of mutation heterogeneity in the Italian population.Blood Cells Mol Dis. 2000;26:417–422.CrossRefPubMedGoogle Scholar
  25. 25.
    Willig TN, Niemeyer CM, Leblanc T, et al. Identification of new prognosis factors from the clinical and epidemiologic analysis of a registry of 229 Diamond-Blackfan anemia patients: DBA group of Societe d’Hematologie et d’Immunologie Pediatrique (SHIP), Gesellshaft fur Padiatrische Onkologie und Hamatologie (GPOH), and the European Society for Pediatric Hematology and Immunology (ESPHI).Pediatr Res. 1999;46:553–561.CrossRefPubMedGoogle Scholar
  26. 26.
    Dianzani I, Garelli E, Ramenghi U. Diamond-Blackfan anaemia: an overview.Paediatr Drugs. 2000;2:345–355.CrossRefPubMedGoogle Scholar
  27. 27.
    Vlachos A, Klein GW, Lipton JM. The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia.J Pediatr Hematol Oncol. 2001;23:377–382.CrossRefPubMedGoogle Scholar
  28. 28.
    Bresters D, Bruin MCA, van Dijken PJ. Congenitale, hypoplastische anemie in Nederland 1963-1989.Tijdschr Kindergeneeskd. 1991;59:203–210.PubMedGoogle Scholar
  29. 29.
    Ramenghi U, Garelli E, Valtolina S, et al. Diamond-Blackfan anaemia in the Italian population.Br J Haematol. 1999;104:841–848.CrossRefPubMedGoogle Scholar
  30. 30.
    Imaizumi Y. A recent survey of consanguineous marriages in Japan.Clin Genet. 1986;30:230–233.CrossRefPubMedGoogle Scholar
  31. 31.
    Bejaoui M, Fitouri Z, Sfar MT, Lakhoua R. Failure of immunosuppressive therapy and high-dose intravenous immunoglobulins in four transfusion-dependent, steroid-unresponsive Blackfan-Diamond anemia patients.Haematologica. 1993;78:38–39.PubMedGoogle Scholar
  32. 32.
    Bernini JC, Carrillo JM, Buchanan GR. High-dose intravenous methylprednisolone therapy for patients with Diamond-Blackfan anemia refractory to conventional doses of prednisone.J Pediatr. 1995;127:654–659.CrossRefPubMedGoogle Scholar
  33. 33.
    Vlachos A, Federman N, Reyes-Haley C, Abramson J, Lipton JM. Hematopoietic stem cell transplantation for Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry.Bone Marrow Transplant. 2001;27:381–386.CrossRefPubMedGoogle Scholar
  34. 34.
    Bonno M, Azuma E, Nakano T, et al. Successful hematopoietic reconstitution by transplantation of umbilical cord blood cells in a transfusion-dependent child with Diamond-Blackfan anemia.Bone Marrow Transplant. 1997;19:83–85.CrossRefPubMedGoogle Scholar
  35. 35.
    Vettenranta K, Saarinen UM. Cord blood stem cell transplantation for Diamond-Blackfan anemia.Bone Marrow Transplant. 1997;19:507–508.CrossRefPubMedGoogle Scholar
  36. 36.
    Barker JN, Martin PL, Coad JE, et al. Low incidence of Epstein- Barr virus-associated posttransplantation lymphoproliferative disorders in 272 unrelated-donor umbilical cord blood transplant recipients.Biol Blood Marrow Transplant. 2001;7:395–399.CrossRefPubMedGoogle Scholar
  37. 37.
    Santucci MA, Bagnara GP, Strippoli P, et al. Long-term bone marrow cultures in Diamond-Blackfan anemia reveal a defect of both granulomacrophage and erythroid progenitors.Exp Hematol. 1999;27:9–18.CrossRefPubMedGoogle Scholar
  38. 38.
    Wynn RF, Grainger JD, Carr TF, Eden OB, Stevens RF, Will AM. Failure of allogeneic bone marrow transplantation to correct Diamond-Blackfan anaemia despite haemopoietic stem cell engraftment.Bone Marrow Transplant. 1999;24:803–805.CrossRefPubMedGoogle Scholar
  39. 39.
    Lipton JM, Federman N, Khabbaze Y, et al. Osteogenic sarcoma associated with Diamond-Blackfan anemia: a report from the Diamond-Blackfan Anemia Registry.J Pediatr Hematol Oncol. 2001;23:39–44.CrossRefPubMedGoogle Scholar
  40. 40.
    Haupt R, Dufour C, Dallorso S, Mori PG. Diamond-Blackfan anemia and malignancy: a case report and a review of the literature.Cancer. 1996;77:1961–1962.CrossRefPubMedGoogle Scholar
  41. 41.
    Cmejla R, Blafkova J, Stopka T, Jelinek J, Petrtylova K, Pospisilova D. Ribosomal proteins S3a, S13, S16, and S24 are not mutated in patients with Diamond-Blackfan anemia.Blood. 2001;97:579–580.CrossRefPubMedGoogle Scholar
  42. 42.
    Uechi T, Tanaka T, Kenmochi N. A complete map of the human ribosomal protein genes: assignment of 80 genes to the cytogenetic map and implications for human disorders.Genomics. 2001; 72:223–230.CrossRefPubMedGoogle Scholar
  43. 43.
    Cmejlova J, Pospisilova D, Cmejla R. Transcription factor GATA-4 is not involved in Diamond-Blackfan anaemia.Haematologica. 2002;87:ELT30.PubMedGoogle Scholar
  44. 44.
    Kojima S, Horibe K, Inaba J, et al. Long-term outcome of acquired aplastic anaemia in children: comparison between immunosuppressive therapy and bone marrow transplantation.Br J Haematol. 2000;111:321–328.CrossRefPubMedGoogle Scholar
  45. 45.
    Deeg HJ, Socie G, Schoch G, et al. Malignancies after marrow transplantation for aplastic anemia and Fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients.Blood. 1996;87:386–392.PubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Shouichi Ohga
    • 1
  • Hideo Mugishima
    • 2
  • Akira Ohara
    • 3
  • Seiji Kojima
    • 4
  • Kohji Fujisawa
    • 5
  • Keiko Yagi
    • 6
  • Masamune Higashigawa
    • 7
  • Ichiro Tsukimoto
    • 3
  • for the Aplastic Anemia Committee of the Japanese Society of Pediatric Hematology
  1. 1.Department of PediatricsKyushu UniversityFukuoka
  2. 2.Department of PediatricsNihon University School of MedicineTokyoItabashi-ku
  3. 3.Toho UniversityTokyo
  4. 4.Nagoya UniversityNagoyaTokyo
  5. 5.Jikei University School of MedicineTokyo
  6. 6.Osaka Medical Center and Research Institute for Maternal and Child HealthOsaka
  7. 7.Mie UniversityMieJapan

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