Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients.
Adenosine Deaminase
/ deficiency
Adolescent
Adult
Agammaglobulinemia
/ enzymology
Bone Marrow Failure Disorders
/ enzymology
Child
Child, Preschool
Female
Graft vs Host Disease
/ etiology
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Intercellular Signaling Peptides and Proteins
/ deficiency
Kaplan-Meier Estimate
Male
Retrospective Studies
Severe Combined Immunodeficiency
/ enzymology
Treatment Outcome
Young Adult
Autoinflammation
Bone marrow failure
DADA2
Deficiency of adenosine deaminase 2
Hematopoietic cell transplantation
Immunodeficiency
Inborn error of immunity
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
08
06
2021
accepted:
06
07
2021
pubmed:
30
7
2021
medline:
22
2
2022
entrez:
29
7
2021
Statut:
ppublish
Résumé
Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. HCT is a definitive cure for DADA2 with > 95% survival.
Identifiants
pubmed: 34324127
doi: 10.1007/s10875-021-01098-0
pii: 10.1007/s10875-021-01098-0
pmc: PMC8452581
doi:
Substances chimiques
Intercellular Signaling Peptides and Proteins
0
ADA2 protein, human
EC 3.5.4.4
Adenosine Deaminase
EC 3.5.4.4
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1633-1647Subventions
Organisme : European Research Council
ID : 948959; MORE2ADA2; EU Horizon 2020
Pays : International
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Intramural Research Program
Pays : United States
Organisme : NIH HHS
ID : Cancer Research Center
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : Wellcome Trust
ID : 207556_Z_17_Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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