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

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/m, 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.

Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation

“…However, the first control transplant that was performed with this regimen demonstrated lack of engraftment (Supplementary Fig. 2 ), a toxicity that has also been described clinically with non-myeloablative HCT and PT-Cy, especially in patients with non-malignant diseases 52 – 55 . Both in patients and in our animal model, graft failure likely occurred due to a lack of myeloablative pre-transplant conditioning, especially in a transplant recipient not previously treated with anti-leukemia myelosuppressive chemotherapy.…”

MRI surveillance of boys with X‐linked adrenoleukodystrophy identified by newborn screening: Meta‐analysis and consensus guidelines

“…Within the consensus protocol, a data request was made towards highlighting CCALD cases under the age of three: Notably, five patients between 1 and 3 years old were diagnosed with CCALD indicating that while rare, CCALD can occur in this window 49‐53 . Some of the patients in this age group presented atypically.…”

Allogeneic hematopoietic stem cell transplantation in patients with childhood cerebral adrenoleukodystrophy: A single‐center experience “Better prognosis in earlier stage”

“…Haploidentical HSCT for patients who lack suitable HLA-matched related or unrelated donors seems to be a suitable choice in an urgent situation. 22 Bone marrow is the most preferred stem cell source, especially for related transplantation. Half of the unrelated transplantations were performed with bone marrow as the source.…”