Hematopoietic stem cell transplantation rescues the hematological, immunological and vascular phenotype in DADA2

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 - Copyright © 2017 American Society of Hematology.

PY - 2017/11

Y1 - 2017/11

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. TNF-α 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=1), HLA-matched unrelated (n=9), HLA-mismatched unrelated (n=3), and HLA haploidentical sibling (n=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 18mo (range 5mo to 13yr). Plasma ADA2 enzyme activity normalized in those tested post-HSCT (7/7), as early as D+14 (myeloid engraftment). Post-HSCT hematological autoimmunity (cytopenias) was reported in 4 patients, acute graft versus host disease (GvHD) grade 1 in 2, grade 2 in 3 and grade 3-4 in 1, and moderate chronic GvHD in 1 patient. In conclusion, in 14 patients, HSCT was an effective and definitive treatment for 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. TNF-α 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=1), HLA-matched unrelated (n=9), HLA-mismatched unrelated (n=3), and HLA haploidentical sibling (n=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 18mo (range 5mo to 13yr). Plasma ADA2 enzyme activity normalized in those tested post-HSCT (7/7), as early as D+14 (myeloid engraftment). Post-HSCT hematological autoimmunity (cytopenias) was reported in 4 patients, acute graft versus host disease (GvHD) grade 1 in 2, grade 2 in 3 and grade 3-4 in 1, and moderate chronic GvHD in 1 patient. In conclusion, in 14 patients, HSCT was an effective and definitive treatment for DADA2.

KW - Journal Article

U2 - 10.1182/blood-2017-07-798660

DO - 10.1182/blood-2017-07-798660

M3 - SCORING: Journal article

C2 - 28974505

VL - 130

SP - 2682

EP - 2688

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 24

ER -