Successful treatment of DOCK8 hyper IgE syndrome by haematopoetic stem cell transplantation

H. Boztug (1), C. Karitnig-Weiß (2), B. Ausserer (2), E. Renner (3), M. Albert (3), J. Sawalle-Belohradsky (3), G. Mann (1), C. Peters (1), A. Lawitschka (1), S. Matthes-Martin (1)

Author address: 

(1)St. Anna Kinderspital (Vienna, AT); (2)Krankenhaus Dornbirn (Dornbirn, AT); (3)Dr. von Haunersches Kinderspital, LMU (Munich, DE)

Abstract: 

Hyper IgE Syndrome (HIES) constitute a rare subset of immunodefi ciencies collectively characterized by a trias of increased serum IgE levels, eczematous rash and recurrent skin and pulmonary infections. Autosomal recessive HIES has been found to be associated with mutations of DOCK8. Hitherto, few reports have been published on patients with DOCK8 HIES treated with hematopoetic stem cell transplantation (HSCT). We report about a girl born to non-consanguineous parents who presented with a severe generalized refractory eczema beginning in the fi rst month of life, multiple food allergies, recurrent sinopulmonary infections, chronic mollusca contagiosa and a chronic HSV1 infection of the eye. Extremely high IgE levels of > 30.000 IU/ml and high values for absolute eosinophils were found. A homozygous mutation in DOCK8 (c.850_851delCT; p.L284fsX292) was identifi ed. Examinations before HSCT revealed a solitary lung nodule. Histology and culture after surgical resection showed aspergillus fumigatus. Following a reduced intensity conditioning regimen consisting of fl udarabine, thiotepa, melphalan and ATG the child received bone marrow stem cells (4,05x10 6 /kg CD34+) from a 10/10 matched HLA identical unrelated donor at the age of 3 years. Immunosupression included cyclosporin and mycofenolatmofetil (until day +30). Engraftment with absolute neutrophil counts > 500/μl occurred on day +19. Transplant complications included acute skin GvHD grade II at day + 26 which responded well to systemic steroids as well as a CMV pneumonitis 4 weeks after SCT which was treated with ganciclovir. Soon after transplantation, the eczematous rash and the HSV 1 infection of the eye disappeared, while the chronic mollusca contagiosa infection persisted for several months. Peripheral blood consistently showed >99% donor chimerism in all cell subsets. Cyclosporine was discontinued at day +180. Six months after transplantation the child is in very good health without signs of infection. The skin appears almost unremarkable with only small remnants of molluscum lesions. Food allergies nearly completely disappeared. IgE levels and absolute numbers of eosinophils have normalized. In conclusion, we have shown in a patient that DOCK8 hyper IgE syndrome can be treated successfully with HSCT. To more comprehensively evaluate the risk and benefi t of HSCT in DOCK8 defi ciency a study including HSCT centers worldwide is underway registered at the European Society of Immunode- fi ciencies (ESID)
2012

abstract No: 

O333

Full conference title: 

Annual Meeting of the EBMT, 38th
    • EBMT 38th (2012)