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:

Alternative donor marrow transplantation in children with aplastic anemia using low-dose irradiation and fludarabine-based conditioning

Bone Marrow Transplantation volume 46, pages 1148–1150 (2011)Cite this article

Subjects

Allogeneic BMT is a curative treatment for patients with severe aplastic anemia (SAA). In particular, BMT from a HLA-identical sibling is an established treatment for children with acquired SAA, but the results of alternative donor (AD) transplantation have been less favorable because of the high rates of graft failure and severe acute GVHD.1 However, recent data have shown improvements in the survival of patients receiving unrelated donor (UD) transplantation possibly due to better donor matching attributable to the use of high-resolution HLA typing data.2 Two major studies have been performed in the setting of UD transplantation for SAA. The first is a Japanese study that reported 154 SAA patients undergoing UD transplantation using CY/TBI/anti-thymocyte globulin (ATG) and also CY/limited field irradiation/ATG: 11% showed rejection whereas 56% survived.3 The second involves a group in the USA, which reported a study that tested the deescalating doses of TBI (from 6 to 2 Gy) in combination with CY and ATG in UD transplantation for SAA, and showed the best outcomes in patients receiving 2 Gy, with 8 of 13 patients surviving.4 The current series presents the results of AD transplantation in 13 SAA patients undergoing BMT with the addition of low-dose irradiation to fludarabine (Flu)-based conditioning.

The characteristics of the 13 SAA patients who underwent AD BMT at Tokai University Hospital between September 2001 and May 2008 are shown in Table 1. Of these 13 patients, 12 received prior immunosuppressive therapy, and all were transfusion dependent at the time of AD transplantation. Specifically, the donors were a UD for 11 patients and an HLA mismatched family member for 2 patients. The HLA-incompatible loci are described in Table 1 and detailed data of HLA typing were received from the Japan Marrow Donor Program. Follow-up data were collected on 30 June 2010. Patients were conditioned with 3 Gy thoracoabdominal irradiation (TAI) on day −6, Flu 25 mg/m2 once daily (i.v.) on days −5, −4, −3 and −2 (total dose 100 mg/m2), CY 750 mg/m2 once daily (i.v.) on days −5, −4, −3 and −2 (total dose 3000 mg/m2) and ATG (thymoglobulin; Genzyme, Cambridge, MA, USA) 1.25 mg/kg once daily (i.v.) on days −5, −4, −3 and −2 (total dose 5 mg/kg) Unmanipulated BM was infused on day 0. Ovary and testis shielding during TAI was performed for all patients, and thyroid gland shielding was provided for five successive patients from patient 9 onwards to prevent secondary thyroid cancer. GVHD prophylaxis was carried out with short-term MTX (15 mg/m2 on day 1; 10 mg/m2 on days 3, 6 and 11) and continuous i.v. infusion of tacrolimus 0.02–0.03 mg/kg. Mycophenolate mofetil 15 mg/kg per day (days 14–42) was added for patients who received antigen mismatched donor marrow. All patients were administered G-CSF from day 5 until their neutrophil counts exceeded 1.5 × 109/L.

Table 1 Patient and donor characteristics
Full size table

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

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. Hows J, Szydlo R, Anasetti C, Camitta B, Gajewski J, Gluckman E . Unrelated donor marrow transplants for severe acquired aplastic anemia. Bone Marrow Transplant 1992; 10 (Suppl): 102–106.

    PubMed  Google Scholar 

  2. Maury S, Balère-Appert ML, Chir Z, Boiron JM, Galambrun C, Yakouben K et al. 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 

  3. Kojima S, Matsuyama T, Kato S, Kigasawa H, Kobayashi R, Kikuta A et al. Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Blood 2002; 100: 799–803.

    Article  CAS  PubMed  Google Scholar 

  4. Deeg HJ, Amylon ID, Harris RE, Collins R, Beatty PG, Feig S et al. Marrow transplants from unrelated donors for patients with aplastic anemia: minimum effective dose of total body irradiation. Biol Blood Marrow Transplant 2001; 7: 208–215.

    Article  CAS  PubMed  Google Scholar 

  5. Perez-Albuerne ED, Eapen M, Klein J, Gross TJ, Lipton JM, Baker KS et al. Outcome of unrelated donor stem cell transplantation for children with severe aplastic anemia. Br J Haematol 2008; 141: 216–223.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Rizzo JD, Curtis RE, Socié G, Sobocinski KA, Gilbert E, Landgren O et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood 2009; 113: 1175–1183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bacigalupo A, Locatelli F, Lanino E, Marsh J, Socié G, Maury S et al. Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party. Bone Marrow Transplant 2005; 36: 947–950.

    Article  CAS  PubMed  Google Scholar 

  8. Vassiliou GS, Webb DKH, Pamphilon D, Knapper S, Veys PA . Improved outcome of alternative donor marrow transplantation in children with severe aplastic anaemia using a conditioning regimen containing low-dose total body irradiation, cyclophosphamide and Campath. Br J Haematol 2001; 104: 701–705.

    Article  Google Scholar 

  9. Yabe H, Inoue H, Matsumoto M, Hamanoue S, Koike T, Ishiguro H et al. Allogeneic haematopoietic cell transplantation from alternative donors with a conditioning regimen of low-dose irradiation, fludarabine and cyclophosphamide in Fanconi anaemia. Br J Haematol 2006; 134: 208–212.

    Article  CAS  PubMed  Google Scholar 

  10. Goldberg MA, Antin JH, Guinan EC, Rappeort JM . Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor. Blood 1986; 68: 1114–1118.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Transplantation, Tokai University Hospital, Isehara, Kanagawa, Japan

    M Yabe, S Kato & H Yabe

  2. Department of Pediatrics, Tokai University Hospital, Isehara, Kanagawa, Japan

    T Shimizu, T Morimoto, T Koike, H Takakura, E Suganuma & N Sugiyama

Authors
  1. M Yabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Morimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H Takakura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Suganuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H Yabe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H Yabe.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yabe, M., Shimizu, T., Morimoto, T. et al. Alternative donor marrow transplantation in children with aplastic anemia using low-dose irradiation and fludarabine-based conditioning. Bone Marrow Transplant 46, 1148–1150 (2011). https://doi.org/10.1038/bmt.2010.241

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.241

This article is cited by

Search

Advanced search

Quick links