Stem cell transplantation for pediatric patients with adrenoleukodystrophy: A nationwide retrospective analysis in Japan.

Abstract

BACKGROUND:

Adrenoleukodystrophy (ALD) is an X-linked recessive disorder and 30-40% of patients develop progressive cerebral neurodegeneration. For symptomatic ALD patients, allogeneic stem cell transplantation (SCT) is considered the standard treatment modality to stabilize or prevent the progression of neurological symptoms.

METHODS:

We retrospectively analyzed the transplant outcomes of 99 pediatric patients with cerebral ALD in Japan. The conditioning regimens included Regimen A: fludarabine/melphalan/low-dose total body irradiation (TBI) with brain sparing (n = 39), Regimen B; busulfan/cyclophosphamide ± others (n = 23), Regimen C: melphalan/total lymphoid irradiation/thoracoabdominal irradiation ± anti-T lymphocyte globulin ± fludarabine (n = 27), and Regimen D: others (n = 10).

RESULTS:

The 5-year overall survival (OS) and event-free survival (EFS) of all patients were 90.0% and 72.9%, respectively. The 5-year OS was 100.0% for Regimen A, 91.1% for Regimen B, 84.4% for Regimen C, and 67.5% for Regimen D (p = 0.028). The 5-year EFS was 78.3% for Regimen A, 78.0% for Regimen B, 70.4% for Regimen C, and 48.0% for Regimen D (p = 0.304). The OS marginally improved after 2007 compared with before 2006 (95.3% vs. 85.2%, p = 0.066), due to the improvement of cord blood transplantation (CBT) outcomes after 2007 compared with before 2006 (96.6% vs. 68.4%, p = 0.005). On magnetic resonance imaging of the brain, a reduced Loes score after SCT was only observed in one of the 15 bone marrow transplantation (BMT) patients, but in 5 of the 15 CBT patients (p = 0.173).

CONCLUSIONS:

Our study revealed that a reduced conditioning regimen with fludarabine/melphalan/low-dose TBI provides better outcomes, and the results of CBT significantly improved after 2007.

• Authors: Koji Kato, Hiromasa Yabe, Nobuyuki Shimozawa, Souichi Adachi, Mineo Kurokawa, Yoshiko Hashii, Atsushi Sato, Nao Yoshida, Makiko Kaga, Osamu Onodera, Shunichi Kato, Yoshiko Atsuta, Tomohiro Morio
• Journal: Pediatric transplantation (Pediatr Transplant) Vol. 26 Issue 1 Pg. e14125 (Feb 2022) ISSN: 1399-3046 [Electronic] Denmark
• PMID: 34661325 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley Periodicals LLC.

Topics

• Adolescent
• Adrenoleukodystrophy (mortality, therapy)
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Japan (epidemiology)
• Male
• Retrospective Studies
• Stem Cell Transplantation (methods)
• Survival Analysis
• Transplantation Conditioning (methods)
• Treatment Outcome