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Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation

Bone Marrow Transplantation volume 53, pages 392–399 (2018)Cite this article

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Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources. We describe the outcomes of transplants performed for nine X-ALD patients using haploidentical donors and PT/Cy. Patients received conditioning regimen with fludarabine 150 mg/m2, cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and mycophenolate mofetil. One patient had a primary graft failure and was not eligible for a second transplant. Three patients had secondary graft failure and were successfully rescued with second haploidentical transplants. Trying to improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for 4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17–37 months after transplant). Haploidentical HSCT with PT/Cy is a feasible alternative for X-ALD patients lacking a suitable matched donor. Graft failure has to be addressed in further studies.

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Acknowledgements

We thank all the nurses, physicians, and multidisciplinary staff of the services for excellent patient care delivered to these patients and families.

Author contributions

J.F.F. designed the study, enrolled, and cared for patients, analyzed data, and wrote the paper. C.B. and N.H. designed the study, enrolled, and cared for patients, analyzed data, and reviewed the paper. All the other authors contributed to data collection, patient care, and reviewed the paper.

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Authors and Affiliations

  1. Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil

    Juliana Folloni Fernandes, Fábio Rodrigues Kerbauy, Morgani Rodrigues, Iracema Esteves, Nathalia Halley Silva, Alessandra Prandini Azambuja, Luiz Fernando Mantovani, José Mauro Kutner, Andrea Tiemi Kondo, Andreza Alice Feitosa Ribeiro & Nelson Hamerschlak

  2. Instituto da Criança, Hospital das clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Juliana Folloni Fernandes, Nathalia Halley Silva, Alessandra Prandini Azambuja & Luiz Fernando Mantovani

  3. Bone Marrow Transplantation Department, Hospital de Clinicas da Universidade Federal do Paraná, Curitiba, Brazil

    Carmem Bonfim, Gisele Loth & Cilmara Cristina Kuwahara

  4. Bone Marrow Transplantation Department, Hospital Nossa Senhora das Graças, Curitiba, Brazil

    Carmem Bonfim, Gisele Loth & Cilmara Cristina Kuwahara

  5. Department of Neurology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Clarissa Bueno & Fernando Kok

  6. Centro de Estudos do Genoma Humano da Universidade de São Paulo, São Paulo, Brazil

    Fernando Kok

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  1. Juliana Folloni Fernandes
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  2. Carmem Bonfim
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Correspondence to Nelson Hamerschlak.

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Fernandes, J.F., Bonfim, C., Kerbauy, F.R. et al. Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation. Bone Marrow Transplant 53, 392–399 (2018). https://doi.org/10.1038/s41409-017-0015-2

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