Hematopoietic Stem Cell Transplantation Outcomes for 11 Patients with Dedicator of Cytokinesis 8 (DOCK8) Deficiency

Publication date: Available online 6 April 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Waleed Al-Herz, Julia I. Chu, Jet van der Spek, Raj Raghupathy, Michel J. Massaad, Sevgi Keles, Catherine M. Biggs, Lucinda Cockerton, Janet Chou, Ghassan Dbaibo, Scott A. Elisofon, Rima Hanna-Wakim, Heung Bae Kim, Leslie E. Lehmann, Douglas R. McDonald, Luigi D. Notarangelo, Paul Veys, Talal Chatila, Raif S. Geha, H. Bobby Gaspar, Sung-Yun Pai
BackgroundDedicator of cytokinesis 8 (DOCK8) deficiency can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Reports of outcome are still limited.ObjectiveTo analyze the results of HSCT in patients with DOCK8 deficiency and report whether approaches resulting in mixed chimerism result in clinically relevant immune reconstitution.MethodsWe performed retrospective chart review of 11 patients with DOCK8 deficiency, and measured DOCK8 expression and cytokine production.ResultsOf 11 patients, 7 received HSCT from related and 4 from unrelated donors; nine patients received busulfan-based conditioning regimens. Survival was excellent (10/11 patients alive, 91%), including a patient who had undergone liver transplantation. Patients showed significant improvements in the frequency and severity of infections. While eczema resolved in all, food allergies and high IgE levels persisted in some patients. Lymphopenia, eosinophilia, low numbers of naïve CD8⁺ T cells and switched memory B cells, and Th1/Th2 cytokine imbalance improved in most patients. While 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 and myeloid chimerism (0-46%). Almost all switched memory B cells were of donor origin. All patients including those with mixed chimerism mounted robust antibody responses to vaccination.ConclusionAllogeneic HSCT ameliorated the infectious and atopic symptoms of 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.

Teaser

This retrospective study of 11 patients transplanted for DOCK8 deficiency shows excellent survival, and good immunologic outcome, even in those patients with mixed B cell chimerism.


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