Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency

Abstract

BACKGROUND: Biallelic variations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency with eczema, recurrent bacterial and viral infections, and malignancy. Natural disease outcome is dismal, but allogeneic hematopoietic stem cell transplantation (HSCT) can cure the disease. OBJECTIVE:To determine outcome of HSCT for DOCK8 deficiency and define possible outcome variables. METHODS:We performed a retrospective study of the results of HSCT in a large international cohort of DOCK8-deficient patients. RESULTS:We identified 81 patients from 22 centers transplanted at a median age of 9.7 years (range, 0.7-27.2 years) between 1995 and 2015. After median follow-up of 26 months (range, 3-135 months), 68 (84%) patients are alive. Severe acute (III-IV) or chronic graft versus host disease occurred in 11% and 10%, respectively. Causes of death were infections (n = 5), graft versus host disease (5), multiorgan failure (2), and preexistent lymphoma (1). Survival after matched related (n = 40) or unrelated (35) HSCT was 89% and 81%, respectively. Reduced-toxicity conditioning based on either treosulfan or reduced-dose busulfan resulted in superior survival compared with fully myeloablative busulfan-based regimens (97% vs 78%; P = .049). Ninety-six percent of patients younger than 8 years at HSCT survived, compared with 78% of those 8 years and older (P = .06). Of the 73 patients with chimerism data available, 65 (89%) had more than 90% donor Tcell chimerism at last follow-up. Not all disease manifestations responded equally well to HSCT: eczema, infections, and mollusca resolved quicker than food allergies or failure to thrive. CONCLUSIONS:HSCT is curative in most DOCK8-deficient patients, confirming this approach as the treatment of choice. HSCT using a reduced-toxicity regimen may offer the best chance for survival.Aydin et al.

The first cohort of Iranian patients with hyper immunoglobulin E syndrome: A long‐term follow‐up and genetic analysis

“…Interferon‐α has been used sporadically with mixed results . Hematopoietic stem cell transplantation (HSCT) has been suggested to be curative in a growing number of patients with DOCK8 deficiency, with a resolution of eczema and recurrent infections including viral skin infections . Thus, it is of supreme importance to document the diagnosis of DOCK8 deficiency molecularly as early as possible.…”

“…54 Hematopoietic stem cell transplantation (HSCT) has been suggested to be curative in a growing number of patients with DOCK8 deficiency, with a resolution of eczema and recurrent infections including viral skin infections. 55…”

Allogeneic hematopoietic stem cell and liver transplantation in a young girl with dedicator of cytokinesis 8 protein deficiency

“…Currently, the only curative treatment for DOCK8 deficiency is HSCT . In our patient, decision for HSCT was complicated because of emerging CLD as well as the risk of transplantation‐related complications such as infections, GVHD, and DILI.…”

“…4 As in our case, clinical findings are observed from the first Currently, the only curative treatment for DOCK8 deficiency is HSCT. 12,13 In our patient, decision for HSCT was complicated because In conclusion, successful LT following HSCT is possible in patients with end-stage liver disease in DOCK8 deficiency. The timing of LT is challenging in patients requiring both HSCT and LT since conditioning regimens for HSCT can be highly hepatotoxic and the patients with suboptimal liver function can become decompensated during HSCT.…”

Autosomal recessive hyper‐IgE syndrome successfully treated with hematopoietic stem cell transplantation

“…The first reports of successful transplantation were published in 20108 and since then a few others have been described, with variable success 6. The largest cohort of transplanted DOCK8-deficient patients to date was recently published F I G U R E 2 Photographs of the patient by the age of 9 (9 mo after the transplant).Complete remission of skin findings DermatologyLOPES Et aL.by Aydin et al9 It included 81 patients from 22 centers, with a median age of 9.7 years. The procedure was generally well tolerated.…”