Allogeneic stem cell transplantation with reduced intensity conditioning for patients with adrenoleukodystrophy

Koji Kato; Ryo Maemura; Manabu Wakamatsu; Ayako Yamamori; Motoharu Hamada; Shinsuke Kataoka; Atsushi Narita; Shunsuke Miwata; Yuko Sekiya; Nozomu Kawashima; Kyogo Suzuki; Kotaro Narita; Sayoko Doisaki; Hideki Muramatsu; Hirotoshi Sakaguchi; Kimikazu Matsumoto; Yuka Koike; Osamu Onodera; Makiko Kaga; Nobuyuki Shimozawa; Nao Yoshida

doi:10.1016/j.ymgmr.2018.11.001

Allogeneic stem cell transplantation with reduced intensity conditioning for patients with adrenoleukodystrophy

Mol Genet Metab Rep. 2018 Nov 20:18:1-6. doi: 10.1016/j.ymgmr.2018.11.001. eCollection 2019 Mar.

Authors

Koji Kato¹, Ryo Maemura¹, Manabu Wakamatsu¹, Ayako Yamamori¹, Motoharu Hamada¹, Shinsuke Kataoka¹, Atsushi Narita¹, Shunsuke Miwata¹, Yuko Sekiya¹, Nozomu Kawashima¹, Kyogo Suzuki¹, Kotaro Narita¹, Sayoko Doisaki¹, Hideki Muramatsu¹, Hirotoshi Sakaguchi¹, Kimikazu Matsumoto¹, Yuka Koike², Osamu Onodera², Makiko Kaga³, Nobuyuki Shimozawa⁴, Nao Yoshida¹

Affiliations

¹ Department of Hematology and Oncology, Children' Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
² Department of Neurology, Clinical Neuroscience Branch, Brain Research Institute, Niigata University, Niigata, Japan.
³ Department of Developmental Disorders, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, Japan.
⁴ Division of Genomics Research, Life Science Research Center, Gifu University, Gifu, Japan.

Abstract

Objective: The prognosis of adrenoleukodystrophy (ALD)with neurological involvement is generally dismal; however, allogeneic stem cell transplantation (SCT) is recognized as effective to stabilize or improve the clinical symptoms of ALD. Herein, we report the clinical outcomes of patients with ALD who consecutively underwent allogeneic stem cell transplantation with reduced intensity conditioning at our institution.

Patients: Sixteen patients with ALD, who were symptomatic (n = 14) or presymptomatic (n = 2), received SCT from 2010 to 2016. The stem cell source was cord blood (n = 14), or bone marrow from a human leukocyte antigen identical sibling (n = 2). The conditioning regimen prior to transplantation was reduced intensity and consisted of fludarabine (125 mg/m²), melphalan (140 mg/m²) and low dose total body irradiation (TBI) of 4Gy (n = 15) or 3Gy (n = 1).

Results: Primary engraftment was obtained in 11 patients, and 4 of the 5 patients who lost the primary graft received a second cord blood transplantation and were engrafted. Five years overall and event-free survival were 90.9% and 61.1% respectively, with a median of 45 months (range 16-91). Loes score stabilized or improved by 18 months after transplantation except for patients with internal capsule involvement.

Conclusion: Allogeneic SCT with reduced intensity conditioning for patients with ALD was safely performed without major transplant-related complications even in symptomatic patients and neurological symptoms were stabilized after SCT in patients without internal capsule involvement.

Keywords: ALD, adrenoleukodystrophy; ATG, anti-thymocyte globulin; Adrenoleukodystrophy; Allogeneic stem cell transplantation; BM, bone marrow; BMT, bone marrow transplantation; CB, cord blood; CMV, cytomegalovirus; CSA, cyclosporine A; CY, cyclophosphamide; DQ, developmental quotient; EBV, Epstein-Barr virus; EFS, event free survival; FISH, fluorescent in situ hybridization; FLU, fludarabine; GVHD, graft-versus host disease; Gd, Gadolinium; HHV-6, human herpesvirus-6; HLA, human leukocyte antigen; IC, internal capsule; IQ, intelligence quotient; Loes score; MAC, myeloablative conditioning; MEL, melphalan; MRI, magnetic resonance imaging; MTX, methotrexate; OS, overall survival; RIC, reduced intensity conditioning; SCT, stem cell transplantation; VLCFA, very long chain fatty acid; Very long chain fatty acid.