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

Bone Marrow Transplant. 2018 Apr;53(4):392-399. doi: 10.1038/s41409-017-0015-2. Epub 2018 Jan 12.

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.

MeSH terms

  • Adolescent
  • Adrenoleukodystrophy / therapy*
  • Adult
  • Bone Marrow Transplantation / adverse effects
  • Bone Marrow Transplantation / methods*
  • Child
  • Cyclophosphamide / therapeutic use*
  • Graft Survival
  • Graft vs Host Disease / etiology
  • Humans
  • Male
  • Middle Aged
  • Tissue Donors
  • Transplantation Conditioning / methods
  • Transplantation, Haploidentical / methods*
  • Treatment Outcome
  • Young Adult

Substances

  • Cyclophosphamide