Khushnuma Mullanfiroze, United Kingdom
Great Ormond Street Hospital PaediatricsPresenter of 1 Presentation
HIGH SUCCESS RATE BUT IMMUNE DYSREGULATION FOLLOWING REDUCED INTENSITY HSCT FOR DOCK8 DEFICIENCY- LONG TERM FOLLOW UP FROM A SINGLE CENTRE
Abstract
Background and Aims
DOCK8 deficiency is a combined immunodeficiency characterised by susceptibility to viral, bacterial infections, malignancies and immunodysregulation. Haematopoietic stem cell transplant (HSCT) offers a cure but data on long term immune reconstitution and post-HSCT inflammatory complications are limited.
Methods
Retrospective case notes audit of patients treated at Great Ormond Street Hospital, London.
Results
Ten children from 8 families underwent HSCT for DOCK8 deficiency from 2000-2018. Median age at HSCT was 9.4 years. Reduced intensity conditioning(RIC) with busulphan or melphalan with fludarabine and serotherapy was used. Four patients underwent matched sibling donor and 6 patients underwent 9/10 (n=3) or 10/10 (n=3) matched unrelated donor HSCT with bone marrow and peripheral blood stem cells respectively. Median follow-up post-HSCT was 71 months (3-191 months) and overall survival was 90%. One child died at day+98 due to rubella encephalitis. 5/9 surviving patients had 100% donor chimerism. The other 4 had >80% CD3-donor chimerism with myeloid engraftment of 0-54%. Of 9 surviving patients, three developed de novo immunodysregulation (inflammatory bowel disease, autoimmune thyroiditis, inflammatory skin lesions) 12 months post-HSCT. Two of these three had full donor chimerism. All evaluable patients had excellent immune reconstitution with age appropriate thymopoiesis post-HSCT. Two patients (with low class switch memory B-cells post-HSCT) developed early loss of serotype specific pneumococcal antibodies following revaccination.
Conclusions
RIC-HSCT offers a cure from the serious complications of DOCK8 deficiency. Mixed chimerism with high donor T-cell engraftment appears sufficient to ameliorate the major manifestations of this disorder however post-HSCT immunodysregulation may persist despite full donor chimerism.