Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly

Janda, Aleš; Sedláček, Petr; Hönig, Manfred; Friedrich, Wilhelm; Champagne, Martin A.; Matsumoto, Tadashi; Fischer, Alain; Neven, Bénédicte; Contet, Audrey; Bensoussan, D.; Bordigoni, Pierre; Loeb, David M.; Savage, William; Jabado, Nada; Bonilla, Francisco A.; Slatter, Mary; Davies, E. Graham; Gennery, Andrew R.

doi:10.1182/blood-2010-03-275966

Cited by 77 publications

(82 citation statements)

References 24 publications

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“…Restoring a functional thymic stromal environment is expected to provide a long-lasting immune reconstitution [3,4]. In complete DiGeorge syndrome, it has been observed that HSCT did not result in a high-quality immune reconstitution [22,[58][59][60][61].…”

Section: Focus On Therapy and Long-term Outcome: Hsct And Thymus Tranmentioning

confidence: 99%

FOXN1 Deficiency: from the Discovery to Novel Therapeutic Approaches

et al. 2017

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Since the discovery of FOXN1 deficiency, the human counterpart of the nude mouse, a growing body of evidence investigating the role of FOXN1 in thymus and skin, has been published. FOXN1 has emerged as fundamental for thymus development, function, and homeostasis, representing the master regulator of thymic epithelial and T cell development. In the skin, it also plays a pivotal role in keratinocytes and hair follicle cell differentiation, although the underlying molecular mechanisms still remain to be fully elucidated. The nude severe combined immunodeficiency phenotype is indeed characterized by the clinical hallmarks of athymia with severe T cell immunodeficiency, congenital alopecia, and nail dystrophy. In this review, we summarize recent discoveries in the field and give interesting perspective about new and promising therapeutic approaches for disorders of immune system with athymia.

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Section: Focus On Therapy and Long-term Outcome: Hsct And Thymus Tranmentioning

confidence: 99%

FOXN1 Deficiency: from the Discovery to Novel Therapeutic Approaches

et al. 2017

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“…Unlike patients with other forms of severe combined immunodeficiency, the absence of T lymphocytes is due to an absence of thymic environment rather than an intrinsic hematopoietic defect. Patients receiving hematopoietic stem cells can achieve peripheral engraftment of post-thymic donor T lymphocytes, but do not demonstrate ongoing T lymphopoiesis [53]. Indeed, T lymphocyte-depleted grafts unsurprisingly fail to demonstrate donor T lymphopoiesis [19].…”

Section: Adoptive Transfer Of Mature T Lymphocytesmentioning

confidence: 99%

“…Indeed, T lymphocyte-depleted grafts unsurprisingly fail to demonstrate donor T lymphopoiesis [19]. Adoptive transfer of cells of hematopoietic origin, achieving longterm survival of the patient, has been published in a few cases only [53,54]. Overall survival is poor (41-48%) as compared to other forms of severe combined immunodeficiency ([80%) ( Table 3) [55].…”

Section: Adoptive Transfer Of Mature T Lymphocytesmentioning

confidence: 99%

“…Overall survival is poor (41-48%) as compared to other forms of severe combined immunodeficiency ([80%) ( Table 3) [55]. Severe pre-existing medicosurgical conditions are a major cause of death, as is graft versus host disease (GvHD), which often seems more severe than expected given that most patients receive cells from well-HLA-matched donors, and not all receive chemotherapy conditioning [53]. Indeed, it could be argued that there is no rational for giving chemotherapy prior to transplantation, except perhaps in patients with oligoclonal T lymphocytes and an Omenn-like presentation, as there is no requirement for donor myeloid cells or B lymphocytes, and lymphocyte progenitors will not lead to T lymphopoiesis given the lack of thymic machinery.…”

Section: Adoptive Transfer Of Mature T Lymphocytesmentioning

confidence: 99%

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Immunological aspects of 22q11.2 deletion syndrome

Gennery

2011

Cell. Mol. Life Sci.

101

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Chromosome 22q11 deletion is the most common chromosomal deletion syndrome and is found in the majority of patients with DiGeorge syndrome and velo-cardio-facial syndrome. Patients with CHARGE syndrome may share similar features. Cardiac malformations, speech delay, and immunodeficiency are the most common manifestations. The immunological phenotype may vary widely between patients. Severe T lymphocyte immunodeficiency is rare-thymic transplantation offers a new approach to treatment, as well as insights into thymic physiology and central tolerance. Combined partial immunodeficiency is more common, leading to recurrent sinopulmonary infection in early childhood. Autoimmunity is an increasingly recognized complication. New insights into pathophysiology are reviewed.

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“…Most likely, thymic engraftment of lymphatic precursors was hampered by the occupation of thymic niches by autologous ZAP-70-deficient precursor cells. This approach to restore a T-cell system just by peripheral expansion of mature T cells has previously been described to be successful in single cases with complete thymic aplasia due to DiGeorge syndrome, 5 and it may be particularly attractive in diseases with defects strictly confined to the T-cell system (ZAP-70 deficiency, CD3-deficiencies and DiGeorge syndrome), 5 as autologous B cells will resume normal function once adequate T-cell help is established as demonstrated here. Although the long-term stability of immune functions in our patient provided by the expansion of transfused donor T cells cannot be predicted, our findings indicate that the strategy of transfusing peripheral T cells derived from an HLA-identical sibling donor as the sole therapeutical maneuver can be a potentially life-saving procedure.…”

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confidence: 99%