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Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency.

ABSTRACT: Dedicator of cytokinesis 8 (DOCK8) deficiency can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Reports of outcomes are still limited.We sought to analyze the results of HSCT in patients with DOCK8 deficiency and report whether approaches resulting in mixed chimerism result in clinically relevant immune reconstitution.We performed a retrospective chart review of 11 patients with DOCK8 deficiency and measured DOCK8 expression and cytokine production.Of 11 patients, 7 received HSCT from related and 4 from unrelated donors; 9 patients received busulfan-based conditioning regimens. Survival was excellent (10 [91%] of 11 patients alive), including a patient who had undergone liver transplantation. Patients showed significant improvements in the frequency and severity of infections. Although eczema resolved in all, food allergies and high IgE levels persisted in some patients. Lymphopenia, eosinophilia, low numbers of naive CD8(+) T cells and switched memory B cells, and TH1/TH2 cytokine imbalance improved in most patients. Although the 8 matched related or unrelated donor recipients had full donor chimerism, all 3 recipients of mismatched unrelated donor HSCT had high levels of donor T-cell chimerism and low B-cell and myeloid cell chimerism (0% to 46%). Almost all switched memory B cells were of donor origin. All patients, including those with mixed chimerism, mounted robust antibody responses to vaccination.Allogeneic HSCT ameliorated the infectious and atopic symptoms of patients with DOCK8 deficiency. In patients with mixed chimerism, selective advantage for donor-derived T cells and switched memory B cells promoted restoration of cellular and humoral immunity and protection against opportunistic infection.

SUBMITTER: Al-Herz W

PROVIDER: S-EPMC5354354 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency.

Al-Herz Waleed W Chu Julia I JI van der Spek Jet J Raghupathy Raj R Massaad Michel J MJ Keles Sevgi S Biggs Catherine M CM Cockerton Lucinda L Chou Janet J Dbaibo Ghassan G Elisofon Scott A SA Hanna-Wakim Rima R Kim Heung Bae HB Lehmann Leslie E LE McDonald Douglas R DR Notarangelo Luigi D LD Veys Paul P Chatila Talal A TA Geha Raif S RS Gaspar H Bobby HB Pai Sung-Yun SY

The Journal of allergy and clinical immunology 20160406 3

<h4>Background</h4>Dedicator of cytokinesis 8 (DOCK8) deficiency can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Reports of outcomes are still limited.<h4>Objective</h4>We sought to analyze the results of HSCT in patients with DOCK8 deficiency and report whether approaches resulting in mixed chimerism result in clinically relevant immune reconstitution.<h4>Methods</h4>We performed a retrospective chart review of 11 patients with DOCK8 deficiency and measured DOCK8 expr ...[more]

PMID: 27130861

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Project description:Viral reactivation occurs frequently in the context of immunodeficiency and immunosuppression after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and can cause severe complications. The aim of this single-center retrospective analysis was to characterize viral infections in the first year after HSCT, to investigate risk factors and to study the impact of viral infections on transplantation outcome. This will facilitate the identification of at-risk patients and the development of new preventive strategies. 107 pediatric allo-HSCT from January 2005 through December 2015 were analyzed for infections with Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), adenovirus (ADV), herpes simplex virus (HSV) and varicella zoster virus (VZV). Viral infections were detected after 68.2% of transplantations. The viruses most commonly encountered were HHV-6 (36/107) and EBV (30/107). Severe viral disease was rare (7/107) and none of the patients died as result of viral reactivation. Important risk factors for viral infections were higher age at HSCT, donor type and occurrence of acute graft-versus-host disease (aGvHD). Especially for EBV, transplant from an unrelated donor and in-vivo T-cell depletion (TCD) had a significant effect on infection rates, whereas for CMV the strongest effect was seen by donor and recipient serostatus with recipient seropositivity most predictive for reactivation. The occurrence of severe aGvHD was associated with EBV and ADV infections. For HSV, the recipient serostatus was identified as prognostic factor for HSV infections, while we found higher age at time of HSCT as risk factor for VZV infections. The overall survival of patients with or without viral infections did not differ significantly. Interestingly, when looking at the 85 patients in our cohort who had received an HSCT for a malignant disease, a tendency towards lower relapse rates was seen in patients affected by viral infections (HR 0.51, 95% CI 0.25 - 1.06, p = 0.072). Viral reactivations are common after pediatric allo-HSCT, though severe complications were rare in our collective. Determining risk factors for viral reactivations may help to identify patients in need of intensified monitoring and to individualize preventive strategies.

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Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency.

Publications

Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency.

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