1.
[Inborn error of metabolism and allogenic hematopoietic cell transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]
Jubert, C., De Berranger, E., Castelle, M., Dalle, J. H., Ouachee-Chardin, M., Sevin, C., Yakoub-Agha, I., Brassier, A.
Bulletin du cancer. 2022
Abstract
Inherited Metabolic Diseases (IMD) are rare genetic diseases, including both lysosomal and peroxisomal diseases. Lysosomal diseases are related to the deficiency of one or more lysosomal enzymes or transporter. Lysosomal diseases are progressive and involve several tissues with most often neurological damage. Among peroxisomal diseases, X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disease combining neurological and adrenal damage. For these diseases, enzyme replacement therapy (ERT), allogeneic hematopoietic cell transplantation (allo-HCT) and gene therapy represent various possible treatment options, used alone or in combination. The purpose of this workshop is to describe the indications, modalities, and follow-up of allo-HCT as well as the use of ERT peri-transplant. All indications for transplant in these rare diseases are associated with comorbidities and are subject to criteria that must be discussed in a dedicated national multidisciplinary consultation meeting. There are some consensual indications in type I-H mucopolysaccharidosis (MPS-IH) and in the cerebral form of ALD. For other IMDs, no clear benefit from the transplant has been demonstrated. The ideal donor is a non-heterozygous HLA-identical sibling. The recommended conditioning is myeloablative combining fludarabine and busulfan. In MPS-IH, ERT has to be started at diagnosis and continued until complete chimerism and normal enzyme assay are achieved. The pre-transplant assessment and post-transplant follow-up are made according to the published recommendations (PNDS). Standard follow-up is carried out jointly by the transplant and referral teams.
2.
Stem cell transplantation for congenital dyserythropoietic anemia. An analysis from the European society for blood and marrow transplantation
Miano, M., Eikema, D. J., Aljurf, M., Van't Veer, P. J., Ozturk, G., Wolfl, M., Smiers, F., Schulz, A., Socie, G., Vettenranta, K., et al
Haematologica. 2019
3.
Survival and Functional Outcomes in Boys with Cerebral Adrenoleukodystrophy with and without Hematopoietic Stem Cell Transplantation
Raymond, G. V., Aubourg, P., Paker, A., Escolar, M., Fischer, A., Blanche, S., Baruchel, A., Dalle, J. H., Michel, G., Prasad, V., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Cerebral adrenoleukodystrophy (CALD) is a rapidly progressing, often fatal, neurodegenerative disease caused by mutations in the ABCD1 gene resulting in deficiency of ALD protein. Clinical benefit has been reported following allogeneic hematopoietic stem cell transplantation (HSCT). A large, multicenter, retrospective chart review to characterize the natural history of CALD, describe outcomes after HSCT, and identify predictors of treatment outcomes was conducted. Major Functional Disabilities (MFDs) were identified as having the most significant impact on CALD patients' abilities to function independently and were used to assess HSCT outcome. Neurologic function score (NFS) and Loes MRI score were assessed. Data were collected on 72 CALD patients who did not undergo HSCT (Untreated cohort) and 65 who were transplanted (HSCT cohort) at 5 clinical sites. Kaplan-Meier (KM) estimates of 5-year overall survival (OS) rates from time of CALD diagnosis were 55% (95% CI, 42.2%-65.7%) for the Untreated cohort and 78% (95% CI, 64%-86.6%) for the HSCT cohort overall (p=0.01). KM-estimates of 2-year MFD-free survival for patients with gadolinium-enhanced lesions (GdE+) were 29% (95% CI, 11.7%-48.2%) for Untreated patients (N=21). For patients transplanted with GdE+ at baseline, with an NFS ≤1 and Loes 0.5 to ≤9 (N=27), 2-year MFD free survival was 84% (95% CI, 62.3%-93.6%). Mortality rates post-HSCT were 8% (100-day, 5/65) and 18% (1-year, 12/65), with disease progression (44%, 7/16) and infection (31%, 5/16) listed as the most common causes of death. Adverse events post-HSCT included infection (29%, 19/65), acute grade II-IV graft-versus-host disease (GVHD; 31%, 18/58), and chronic GVHD (7%, 4/58). Eighteen percent (12/65) of patients experienced engraftment failure after their first HSCT. Positive predictors of OS in the HSCT cohort may include donor/recipient human leukocyte antigen-matching and lack of GVHD, and early disease treatment was a predictor of MFD-free survival. GdE+ is a strong predictor of disease progression in untreated patients. This study confirms HSCT as an effective treatment for CALD when performed early. We propose survival without MFDs as a relevant treatment goal, rather than only assessing overall survival as an indicator of treatment success.