Haploidentical stem cell transplantation in DOCK8 deficiency — Successful control of pre-existing severe viremia with a TCRaß/CD19-depleted graft and antiviral treatment

Ghosh, Sujal; Schuster, Friedhelm R.; Adams, Ortwin; Babor, Florian; Borkhardt, Arndt; Comoli, Patrizia; Handgretinger, Rupert; Lang, Peter; Hj, Laws; Siepermann, Meinolf; Meisel, Roland

doi:10.1016/j.clim.2014.03.006

Cited by 27 publications

(23 citation statements)

References 9 publications

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“…However, all of these modalities seem to have partial efficacy or have been limited by side effects when they have been used in a larger number of DIDS patients, making them more suitable as adjunctive therapy (13). In contrast, the only form of definitive therapy, borne out through the experience of multiple centers, has been hematopoietic stem cell transplantation (HSCT) (24-31). HSCT for DIDS has been successfully performed using reduced intensity myeloablative conditioning regimens with matched related or matched unrelated allogeneic donor cells (24-26, 29, 30).…”

Section: Clinical Progression Of Disease and Its Treatmentmentioning

confidence: 99%

Recent Advances in DOCK8 Immunodeficiency Syndrome

Zhang

Jing

2016

J Clin Immunol

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Since the discovery of the genetic basis of DOCK8 immunodeficiency syndrome (DIDS) in 2009, several hundred patients worldwide have been reported, validating and extending the initial clinical descriptions. Importantly, the beneficial role of hematopoietic stem cell transplantation for this disease has emerged, providing impetus for improved diagnosis. Additionally, several groups have further elucidated the biological functions of DOCK8 in the immune system that help explain disease pathogenesis. Here, we summarize these recent developments.

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Section: Clinical Progression Of Disease and Its Treatmentmentioning

confidence: 99%

Recent Advances in DOCK8 Immunodeficiency Syndrome

Zhang

Jing

2016

J Clin Immunol

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“…However, this method leads to prolonged immunoincompetence in patients, resulting in a high incidence of infections and associated complications, which affect the outcome of HSCT [3].…”

Section: Introductionmentioning

confidence: 99%

Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαβ and CD19 Depletion in Children with Primary Immunodeficiency Syndromes

Balashov

Shcherbina

Maschan

et al. 2015

Biology of Blood and Marrow Transplantation

140

103

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The transplantation of stem cells from a matched unrelated donor (MUD) or a haploidentical mismatched related donor (MMRD) is a widely used variant of curative treatment for patients with primary immunodeficiency (PID). Currently, different strategies are used to reduce the risk of post-transplant complications and enhance immune reconstitution. We report the preliminary results of MUD and MMRD transplantation with TCRαβ/CD19 depletion in patients with PID (trial registered at www.clinicaltrials.gov as NCT02327351). Thirty-seven PID patients (median age, 2.6 years; range, .2 to 17) were transplanted from MUDs (n = 27) or haploidentical MMRDs (n = 10) after TCRαβ(+)/CD19(+) graft depletion. The median numbers of CD34(+) and TCRαβ(+) cells in the graft were 11.7 × 10(6)/kg and 10.6 × 10(3)/kg, respectively. Acute graft-versus-host disease (GVHD) was observed in 8 patients (22%), without a statistically significant difference between MUDs and MMRDs; 7 of these patients had grade II acute GVHD and responded to first-line therapy, whereas 1 patient had grade IV acute GVHD with transformation to extensive chronic GVHD. Primary and secondary graft failure (nonengraftment or rejection) was observed in 10 patients (27%), 9 of whom were treated with 1 alkylating agent in the conditioning regimen. All these patients were successfully retransplanted with different rescue protocols. Preliminary data on immune reconstitution were very encouraging. Most patients had significant numbers of T lymphocytes detected on the first assessment (day +30) and more than 500 T cells/μL, on day +120. Based on our preliminary data, no significant difference was seen between MMRD and MUD hematopoietic stem cell transplantation (HSCT). With a median follow-up period of 15 months, the cumulative probabilities of overall patient survival and transplant-related mortality were 96.7% and 3.3%, respectively. Based on the results, the ability to control the main post-transplant complications and the immune reconstitution rates are the main factors leading to successful outcome in patients with PID after TCRαβ(+)-depleted HSCT.

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“…14 This approach leaves gd T cells and natural killer (NK) cells in the donor graft, allowing control of intercurrent infections but minimizing the risk for GVHD. 15,16 CONDITIONING REGIMEN Variability in the underlying molecular cause of disease in various PIDDs dictates that a disease-specific approach to conditioning should be taken. In some PIDDs such as DNA repair disorders, the molecular defect that causes immunodeficiency also results in radiation sensitivity, so radiation therapy should be avoided or used with caution.…”

Section: Stem Cell Graft Manipulationmentioning

confidence: 99%