Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Successful first-line treatment with double umbilical cord blood transplantation in severe aplastic anemia

Bone Marrow Transplantation volume 45, pages 955–956 (2010)Cite this article

Patients with severe aplastic anemia (SAA) who lack an appropriate matched related donor usually receive immunosuppressive therapy (IST), and those who fail it undergo transplantation from an HLA-matched unrelated donor. However, the treatment for failure after IST or unrelated transplantation has not been satisfactory. Recently, promising results were reported by many groups for umbilical cord blood transplantation (UCBT) as a salvage therapy, including transplantation with two units to overcome the cell-dose barrier of cord blood.1, 2, 3, 4 On the basis of these promising results, a boy with acquired SAA was successfully treated with double UCBT as a first-line treatment.

A 10-year-old boy, blood type B+, was admitted to our hospital because of pale appearance. His initial peripheral blood counts showed 2.9 × 109/l WBC with 7.4% neutrophils, 89.2% lymphocytes and 2.7% monocytes; 4.6 g per 100 ml hemoglobin with a hematocrit of 13.0; 2.1% reticulocytes and a plt count of 14 × 109/l. The BM study revealed a hypocellular marrow (0–10% cellularity) with a decrease in normal hematopoietic cells. This led to the diagnosis of SAA. As the patient had no siblings, we searched for a matched unrelated donor without success, but we did find two units of umbilical cord blood suitable for transplantation. Selection of the cord blood units was based on HLA-A and HLA-B low-resolution typing and HLA-DRB1 high-resolution typing. Before transplantation, the patient received a transfusion of six units of packed RBC. He did not receive any IST. We explained the current results of IST and UCBT treatment to the patient's parents, and obtained written informed consent before performing a double UCBT 5 months after the diagnosis (26 July 2007). The conditioning regimen consisted of cyclophosphamide (60 mg/kg once daily i.v. on days –9 and –8), fludarabine (30 mg/m2 once daily i.v. on days –7, –6, –5, –4, –3 and –2), and TBI (3 Gy on day –1). GvHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Other supportive care was given according to the guidelines of our center for SCT.1 Engraftment was achieved with one unit from an O+ male containing 4.0 × 107/kg nucleated cells and 1.5 × 105/kg CD34+ cells, 1.4 × 104/kg CFU-GM and matched for 5/6 HLA antigens. However, another unit from a B+ female matched for 4/6 HLA Ags and containing 5.6 × 107/kg nucleated cells with 1.0 × 105/kg CD34+ cells and 1.0 × 104/kg CFU-GM disappeared. The number of days required to reach an ANC >0.5 × 109/l and 1.0 × 109/l was 15 and 16 days, respectively. Spontaneous plt recovery to >20 × 109/l and 100 × 109/l required 30 and 33 days, respectively. Complete donor-type chimerism was confirmed through the analysis of STR regions. At 12 days after transplantation, engraftment syndrome developed with fever, rash and pulmonary edema and was treated with methylprednisolone. Grade II acute graft-versus-host disease developed and was controlled with steroid treatment. The patient was treated with ganciclovir for CMV antigenemia detected on routine surveillance. At 40 days after transplantation, pneumonia developed and the patient received antibiotics and antifungal agents for 3 weeks. Up to about 2 years after the double UCBT, the patient has been well without any complications. Although mixed chimerism of the patient with two units was detected in a sample from peripheral blood 7 days after UCBT, complete donor-type chimerism with only one unit was achieved 14 days after UCBT and has been maintained in samples from BM and peripheral blood with a normal blood cell count.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Kang HJ, Kho SH, Jang MK, Lee SH, Shin HY, Ahn HS . Early engraftment kinetics of two units cord blood transplantation. Bone Marrow Transplant 2006; 38: 197–201.

    Article  CAS  PubMed  Google Scholar 

  2. Yoshimi A, Kojima S, Taniguchi S, Hara J, Matsui T, Takahashi Y et al. Japan Cord Blood Bank Network. Unrelated cord blood transplantation for severe aplastic anemia. Biol Blood Marrow Transplant 2008; 14: 1057–1063.

    Article  CAS  PubMed  Google Scholar 

  3. Chan KW, McDonald L, Lim D, Grimley MS, Grayson G, Wall DA . Unrelated cord blood transplantation in children with idiopathic severe aplastic anemia. Bone Marrow Transplant 2008; 42: 589–595.

    Article  CAS  PubMed  Google Scholar 

  4. Ruggeri A, de Latour RP, Rocha V, Larghero J, Robin M, Rodrigues CA et al. Double cord blood transplantation in patients with high risk bone marrow failure syndromes. Br J Haematol 2008; 143: 404–408.

    Article  CAS  PubMed  Google Scholar 

  5. Kennedy-Nasser AA, Leung KS, Mahajan A, Weiss HL, Arce JA, Gottschalk S et al. Comparable outcomes of matched-related and alternative donor stem cell transplantation for pediatric severe aplastic anemia. Biol Blood Marrow Transplant 2006; 12: 1277–1284.

    Article  PubMed  Google Scholar 

  6. Maury S, Balere-Appert ML, Chir Z, Boiron JM, Galambrun C, Yakouben K et al. French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient. Haematologica 2007; 92: 589–596.

    Article  PubMed  Google Scholar 

  7. Locasciulli A, Oneto R, Bacigalupo A, Socie G, Korthof E, Bekassy A et al. Severe Aplastic Anemia Working Party of the European Blood and Marrow Transplant Group. Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT). Haematologica 2007; 92: 11–18.

    Article  CAS  PubMed  Google Scholar 

  8. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947–1954.

    Article  PubMed  Google Scholar 

  9. Majhail NS, Brunstein CG, Wagner JE . Double umbilical cord blood transplantation. Curr Opin Immunol 2006; 18: 571–575.

    Article  CAS  PubMed  Google Scholar 

  10. Yoo KH, Lee SH, Kim HJ, Sung KW, Jung HL, Cho EJ et al. The impact of post-thaw colony-forming units-granulocyte/macrophage on engraftment following unrelated cord blood transplantation in pediatric recipients. Bone Marrow Transplant 2007; 39: 515–521.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health, Welfare and Family Affairs, Republic of Korea (A080588) and by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006-E00327).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

    H J Kang, J W Lee, H Kim, H Y Shin & H S Ahn

Authors
  1. H J Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J W Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Y Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H S Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H Y Shin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kang, H., Lee, J., Kim, H. et al. Successful first-line treatment with double umbilical cord blood transplantation in severe aplastic anemia. Bone Marrow Transplant 45, 955–956 (2010). https://doi.org/10.1038/bmt.2009.247

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.247

This article is cited by

Search

Advanced search

Quick links