Successful Long-Term Correction of Autosomal Recessive Hyper-IgE Syndrome due to DOCK8 Deficiency by Hematopoietic Stem Cell Transplantation

Bittner, Tanja C.; Pannicke, Ulrich; Renner, Ellen D.; Notheis, Gundula; Hoffmann, Friedrich; Belohradsky, Bernd H.; Wintergerst, Uwe; Häuser, Markus; Klein, Benjamin Y.; Schwarz, Klaus; Schmid, Irene; Albert, MH

doi:10.1055/s-0030-1265135

Cited by 83 publications

(76 citation statements)

References 20 publications

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“…DOCK8 deficiency is associated with a high degree of morbidity and mortality—including life-threatening infections and virus-driven malignancies—with an estimated overall survival of 50% at 20 years [3]. Allogeneic hematopoietic stem cell transplantation (HSCT) represents a curative therapy for DOCK8 deficiency [6-14]. …”

Section: Introductionmentioning

confidence: 99%

Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide

Shah

Freeman

et al. 2017

Biology of Blood and Marrow Transplantation

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Dedicator-of-cytokinesis 8 (DOCK8) deficiency, a primary immunodeficiency disease, can be reversed by allogeneic hematopoietic stem cell transplantation (HSCT); however, there are few reports describing the use of alternative donor sources for HSCT in DOCK8 deficiency. We describe HSCT for patients with DOCK8 deficiency who lack a matched related or unrelated donor using bone marrow from haploidentical related donors and post-transplantation cyclophosphamide (PT/Cy) for graft-versus-host disease (GVHD) prophylaxis. Seven patients with DOCK8 deficiency (median age, 20 years; range, 7 to 25 years) received a haploidentical related donor HSCT. The conditioning regimen included 2 days of low-dose cyclophosphamide, 5 days of fludarabine, 3 days of busulfan, and 200 cGy total body irradiation. GVHD prophylaxis consisted of PT/Cy 50 mg/kg/day on days +3 and +4 and tacrolimus and mycophenolate mofetil starting at day +5. The median times to neutrophil and platelet engraftment were 15 and 19 days, respectively. All patients attained >90% donor engraftment by day +30. Four subjects developed acute GVHD (1 with maximum grade 3). No patient developed chronic GVHD. With a median follow-up time of 20.6 months (range, 9.5 to 31.7 months), 6 of 7 patients are alive and disease free. Haploidentical related donor HSCT with PT/Cy represents an effective therapeutic approach for patients with DOCK8 deficiency who lack a matched related or unrelated donor.

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Section: Introductionmentioning

confidence: 99%

Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide

Shah

Freeman

et al. 2017

Biology of Blood and Marrow Transplantation

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“…It should be considered as early as possible, given the gradual worsening of the disease. [19][20][21][22] Hematopoietic stem cell transplantation has also shown dramatic positive outcomes in various autoimmune diseases, including SLE. 23 …”

Section: Discussionmentioning

confidence: 99%

Ten-Year Follow-Up of a DOCK8-Deficient Child With Features of Systemic Lupus Erythematosus

Jouhadi¹,

Khadir²,

Ailal³

et al. 2014

Pediatrics

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Dedicator of cytokinesis 8 (DOCK8) deficiency is an innate error of adaptive immunity characterized by recurrent infections with viruses, bacteria, and fungi, typically high serum levels of immunoglobulin E, eosinophilia, and a progressive deterioration of T-and B-cell-mediated immunity. DOCK8 mutations are the second most common cause of hyper-immunoglobulin E syndromes (HIES). We report a case of DOCK8 deficiency associated with systemic lupus erythematosus (SLE). Association of SLE with HIES is very rare; to our knowledge, this is the sixth such case reported in the literature. A 10-year-old girl of consanguineous parents was followed in our clinic because of HIES since early childhood. She developed SLE with purpuric and necrotic skin lesions, diffuse arthritis, and glomerulonephritis. These autoimmune features were corroborated by the presence of antinuclear, anti-DNA, and antiphospholipid antibodies. The combination of HIES and autoimmunity makes treatment difficult, because the use of immunosuppressive drugs needed for SLE may worsen existing symptoms caused by the immunodeficiency. Our observation is the first case of association of SLE with HIES in the literature where the primary immune disease is genetically documented and labeled as DOCK8 deficiency.

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“…Early The autosomal recessive variant may benefit from a hematopoietic stem cell graft. [9] CONCLUSION Early detection with proper care can prevent progression of JS. Initiate treatment at the first signs of infection to prevent long-term complications.…”

Section: Discussionmentioning

confidence: 99%

Tuberculous osteomyelitis in Job syndrome

Shilpa

Singhal

Shimoga

et al. 2013

Indian J Paediatr Dermatol

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Successful Long-Term Correction of Autosomal Recessive Hyper-IgE Syndrome due to DOCK8 Deficiency by Hematopoietic Stem Cell Transplantation

Cited by 83 publications

References 20 publications

Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide

Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide

Ten-Year Follow-Up of a DOCK8-Deficient Child With Features of Systemic Lupus Erythematosus

Tuberculous osteomyelitis in Job syndrome

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