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:

Haploidentical hematopoietic SCT for acquired severe aplastic anemia using post-transplant high-dose CY

Bone Marrow Transplantation volume 50, pages 155–156 (2015)Cite this article

Subjects

Young patients with severe aplastic anemia (SAA) who lack a suitable family donor and fail immunosuppressive therapy (IST) are treated with unrelated donor transplants or a repeat course of IST.1 The outcomes of unrelated allografts have improved in recent years, but are still associated with a high risk of acute and chronic GVHD when compared to matched related donor transplants.2 However, for most of the patients in developing countries matched unrelated donors (MUD) are not available. Other options include cord blood or haploidentical SCT (HaploSCT).3 Cord blood transplantation for acquired SAA has been found to result in high graft failure rates of ~50% and chronic GVHD rates of ~20%.4 T-cell-replete haploSCT using post-transplant CY (PT/CY) has shown high engraftment rates and very low incidences of GVHD in patients with hematologic malignancies.5,6 This strategy has been used in patients with sickle cell anemia7 and recently in four adults with refractory aplastic anemia.8 This strategy has not yet been reported in children with aplastic anemia. We report herein our experience of PT/CY haploSCT in two pediatric patients with refractory aplastic anemia.

An 8-year-old girl was diagnosed with SAA in September 2012. In the absence of a HLA-matched family donor, she was treated with a course of IST (ATGAM 40 mg/kg/day for 4 days and cyclosporine). She did not respond and remained transfusion dependent. She was taken up for haploSCT after 4 months of no response to IST. Patient, donor and transplant characteristics are shown in Table 1. Non-myeloablative conditioning was used as described previously by Luznik et al.:5 fludarabine (30 mg/m2 from day −6 to −2), CY (14.5 mg/kg on day −6 and −5), and TBI (200 cGy on day −1). Prophylaxis against GVHD was CY (50 mg/kg on days +3 and +4), tacrolimus (0.06 mg/kg from day +5 through day +180) and mycophenolate mofetil (10 mg/kg q8h from day +5 through day +35). Peripheral blood stem cells (PBSC) from the father were used for transplant. Both the parents and patient were CMV reactive. She developed neutropenic fever during conditioning and was found to have possible pulmonary aspergillosis, which was treated with amphotericin B. CD34+ cell dose infused was 17.6 × 106 per kg of recipient body weight. Neutrophil and platelets engrafted by day +14 and day +9, respectively. On day +18 she developed grade 2 acute GVHD (gut and liver), which was treated with i.v. methylprednisolone 2 mg/kg/day. Complete resolution of GVHD occurred by day +25. She also had elevation in CMV titers by D+21 to 500 copies/mL, which decreased to <150 copies/mL after a week. By day +35 CMV DNA PCR became undetectable without any treatment. The steroid was tapered off in the next one month without any recurrence of GVHD. Post-engraftment chimerism was done on unfractionated peripheral blood on day +30, which revealed donor cells to be 97%. Tacrolimus was tapered off after 6 months of therapy without recurrence of GVHD. After 6 months of transplant lymphocyte subset analysis revealed inverse CD4 to CD8 ratio with normal B and natural killer cell numbers. Ig levels were in the normal range. After 18 months of transplant complete blood count (CBC) shows Hb 10.3 g/dL, WBC 9.3 × 109/L and platelets 150 × 109/L. She continues to be in complete donor chimerism and has not developed any chronic GVHD.

Table 1 Donor, recipient and transplant characteristics
Full size table

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. Guinan EC . Acquired aplastic anemia in childhood. Hematol Oncol Clin North Am 2009; 23: 171–191.

    Article  Google Scholar 

  2. Bacigalupo A, Socie' G, Lanino E, Prete A, Locatelli F, Locasciulli A et al. Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA Working Party. Haematologica 2010; 95: 976–982.

    Article  CAS  Google Scholar 

  3. Marsh JC, Kulasekararaj AG . Management of the refractory aplastic anemia patient: what are the options? Blood 2013; 122: 3561–3567.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M et al. HLA haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2008; 14: 641–650.

    Article  CAS  Google Scholar 

  6. Fuchs EJ . Human leukocyte antigen-haploidentical stem cell transplantation using T-cell-replete bone marrow grafts. Curr Opin Hematol 2012; 19: 440–447.

    Article  CAS  Google Scholar 

  7. Bolaños-Meade J, Fuchs EJ, Luznik L, Lanzkron SM, Gamper CJ, Jones RJ et al. HLA haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood 2012; 120: 4285–4291.

    Article  Google Scholar 

  8. Raj K, Pagliuca A, Bradstock K, Noriega V, Potter V, Streetly M et al. Peripheral blood hematopoietic stem cells for transplantation of hematological diseases from related, haploidentical donors after reduced-intensity conditioning. Biol Blood Marrow Transplant 2014; 20: 890–895.

    Article  Google Scholar 

  9. Ciceri F, Lupo-Stanghellini MT, Korthof ET . Haploidentical transplantation in patients with acquired aplastic anemia. Bone Marrow Transplant 2013; 48: 183–185.

    Article  CAS  Google Scholar 

  10. Castagna L, Crocchiolo R, Furst S, Bramanti S, El Cheikh J, Sarina B et al. Bone marrow compared with peripheral blood stem cells for haploidentical transplantation with a nonmyeloablative conditioning regimen and post-transplantation cyclophosphamide. Biol Blood Marrow Transplant 2014; 20: 724–729.

    Article  Google Scholar 

Download references

Acknowledgements

NG designed the research and wrote the manuscript; DC designed the research; SKS designed the research and helped in writing the manuscript; VK and MD wrote the manuscript.

Author information

Authors and Affiliations

  1. Department of Hematooncology and Bone Marrow Transplant, BLK Super Specialty Hospital, New Delhi, India

    N Gupta, D Choudhary, S K Sharma, V Khandelwal & M Dhamija

Authors
  1. N Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Choudhary
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S K Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V Khandelwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Dhamija
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Gupta.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gupta, N., Choudhary, D., Sharma, S. et al. Haploidentical hematopoietic SCT for acquired severe aplastic anemia using post-transplant high-dose CY. Bone Marrow Transplant 50, 155–156 (2015). https://doi.org/10.1038/bmt.2014.222

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2014.222

This article is cited by

Search

Advanced search

Quick links