TY - JOUR
T1 - Hematopoietic stem cell transplantation rescues the hematological, immunological, and vascular phenotype in DADA2
AU - Hashem, Hasan
AU - Kumar, Ashish R.
AU - Müller, Ingo
AU - Babor, Florian
AU - Bredius, Robbert
AU - Dalal, Jignesh
AU - Hsu, Amy P.
AU - Holland, Steven M.
AU - Hickstein, Dennis D.
AU - Jolles, Stephen
AU - Krance, Robert
AU - Sasa, Ghadir
AU - Taskinen, Mervi
AU - Koskenvuo, Minna
AU - Saarela, Janna
AU - Van Montfrans, Joris
AU - Wilson, Keith
AU - Bosch, Barbara
AU - Moens, Leen
AU - Hershfield, Michael
AU - Meyts, Isabelle
N1 - Funding Information:
This paper was made possible thanks to the collaboration of the European Society of Blood and Bone Marrow Transplantation, Inborn Errors Working Party, Clinical Immunology Society, Primary Immunodeficiency Transplant Consortium, and the Center for International Blood and Marrow Transplant Research.
Funding Information:
The authors thank the affected children and their parents for their participation and for their confidence; the DADA2 Foundation (www.dada2.org) for its efforts in organizing the Inaugural International Conference on the Deficiency of ADA2; Chip Chambers for forming the foundation; Troy Torgerson and Daniel Kastner for facilitating and for advising on the data collection; Polina Stepensky for sharing invaluable information on patients with PRCA and DADA2; and Nancy J. Ganson and Susan J. Kelly, at Duke University Center, Durham, NC, for the numerous ADA2 enzyme activity measurements.
PY - 2017/12/14
Y1 - 2017/12/14
N2 - Deficiency of adenosine deaminase 2 (DADA2) is caused by biallelic deleterious mutations in CECR1. DADA2 results in variable autoinflammation and vasculopathy (recurrent fevers, livedo reticularis, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency and bone marrow failure. Tumor necrosis factor-a blockade is the treatment of choice for the autoinflammation and vascular manifestations. Hematopoietic stem cell transplantation (HSCT) represents a potential definitive treatment. We present a cohort of 14 patients from 6 countries who received HSCT for DADA2. Indication for HSCT was bone marrow dysfunction or immunodeficiency. Six of 14 patients had vasculitis pre-HSCT. The median age at HSCT was 7.5 years. Conditioning regimens were myeloablative (9) and reduced intensity (5). Donors were HLA-matched sibling (n 5 1), HLA-matched unrelated (n 5 9), HLA-mismatched unrelated (n 5 3), and HLA haploidentical sibling (n 5 1). All patients are alive and well with no new vascular events and resolution of hematological and immunological phenotype at a median follow-up of 18 months (range, 5 months to 13 years). Plasma ADA2 enzyme activity normalized in those tested post-HSCT (7/7), as early as day 114 (myeloid engraftment). Post-HSCT hematological autoimmunity (cytopenias) was reported in 4 patients, acute graft-versus-host disease grade 1 in 2, grade 2 in 3, and grade 3-4 in 1, and moderate chronic graft-versus-host disease in 1 patient. In conclusion, in 14 patients, HSCT was an effective and definitive treatment of DADA2.
AB - Deficiency of adenosine deaminase 2 (DADA2) is caused by biallelic deleterious mutations in CECR1. DADA2 results in variable autoinflammation and vasculopathy (recurrent fevers, livedo reticularis, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency and bone marrow failure. Tumor necrosis factor-a blockade is the treatment of choice for the autoinflammation and vascular manifestations. Hematopoietic stem cell transplantation (HSCT) represents a potential definitive treatment. We present a cohort of 14 patients from 6 countries who received HSCT for DADA2. Indication for HSCT was bone marrow dysfunction or immunodeficiency. Six of 14 patients had vasculitis pre-HSCT. The median age at HSCT was 7.5 years. Conditioning regimens were myeloablative (9) and reduced intensity (5). Donors were HLA-matched sibling (n 5 1), HLA-matched unrelated (n 5 9), HLA-mismatched unrelated (n 5 3), and HLA haploidentical sibling (n 5 1). All patients are alive and well with no new vascular events and resolution of hematological and immunological phenotype at a median follow-up of 18 months (range, 5 months to 13 years). Plasma ADA2 enzyme activity normalized in those tested post-HSCT (7/7), as early as day 114 (myeloid engraftment). Post-HSCT hematological autoimmunity (cytopenias) was reported in 4 patients, acute graft-versus-host disease grade 1 in 2, grade 2 in 3, and grade 3-4 in 1, and moderate chronic graft-versus-host disease in 1 patient. In conclusion, in 14 patients, HSCT was an effective and definitive treatment of DADA2.
UR - http://www.scopus.com/inward/record.url?scp=85033445221&partnerID=8YFLogxK
U2 - 10.1182/blood-2017-07-798660
DO - 10.1182/blood-2017-07-798660
M3 - Article
C2 - 28974505
AN - SCOPUS:85033445221
SN - 0006-4971
VL - 130
SP - 2682
EP - 2688
JO - Blood
JF - Blood
IS - 24
ER -