Clinical and immunological correction of DOCK8 deficiency by allogeneic hematopoietic stem cell transplantation following a reduced toxicity conditioning regimen.
Dedicator of cytokinesis 8 protein (DOCK8) deficiency is a combined immunodeficiency disorder characterized by an expanding clinical picture with typical features of recurrent respiratory or gastrointestinal tract infections, atopic eczema, food allergies, chronic viral infections of the skin, and blood eosinophilia often accompanied by elevated serum IgE levels. The only definitive treatment option is allogeneic hematopoietic stem cell transplantation (HSCT). We report a patient with early severe manifestation of DOCK8 deficiency, who underwent unrelated allogeneic HSCT at the age of 3 years following a reduced toxicity conditioning regimen. The transplant course was complicated by pulmonary aspergilloma pretransplantation, adenovirus (ADV) reactivation, and cytomegalovirus (CMV) pneumonitis 4 weeks after transplantation. With antifungal and antiviral treatment the patient recovered. Seven months after transplantation the patient is in excellent clinical condition. Eczematous rash, chronic viral skin infections, and food allergies have subsided, associated with normalization of IgE levels and absolute numbers of eosinophils. Chimerism analysis shows stable full donor chimerism. DOCK8 deficiency can be successfully cured by allogeneic HSCT. This treatment option should be considered early after diagnosis, as opportunistic infections and malignancies that occur more frequently during the natural course of the disease are associated with higher morbidity and mortality.
Department of Paediatrics, St Anna Kinderspital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria. heidrun.boztug@stanna.at
Heidrun
H
Boztug
Cäcilia
C
Karitnig-Weiß
Bernd
B
Ausserer
Ellen D
ED
Renner
Michael H
MH
Albert
Julie
J
Sawalle-Belohradsky
Bernd H
BH
Belohradsky
Georg
G
Mann
Ernst
E
Horcher
Alexandra
A
Rümmele-Waibel
Rene
R
Geyeregger
Karoly
K
Lakatos
Christina
C
Peters
Anita
A
Lawitschka
Susanne
S
Matthes-Martin
D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D009154:Mutation; D010375:Pedigree; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous
C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors