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Insufficient immune reconstitution after allogeneic cord blood transplantation without chemotherapy conditioning in patients with SCID caused by CD3δ deficiency

Bone Marrow Transplantation volume 51, pages 1131–1133 (2016)Cite this article

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SCID is a heterogeneous group of genetic disorders characterized by profound defect of T- and B-cell function. SCID patients usually die in early childhood unless immune reconstitution by hematopoietic stem cell transplantation (HSCT) or gene therapy can be achieved.1 The most common type of SCID is X-linked SCID (X-SCID), that is, T−B+NK− SCID, caused by mutations of the IL2RG gene.2 The thymus of the X-SCID patients is atrophic due to the defect of T-cell differentiation in the early stage.2 Sufficient T-cell reconstitution is usually obtained by HSCT even without chemotherapy conditioning in these patients over the long term.3 Although these patients might not have significant numbers of multilineage stem cell engraftment, it can offer seeding of T-cell precursor niches sufficient to maintain thymopoiesis.4, 5 HSCT without conditioning provides split chimerism, where T cells derive from the donor and B cells derive from the recipient, respectively, and the recovery of B-cell function is not usually obtained because of the intrinsic defect in recipient B-cell function.6 Thus, many patients require Ig replacement therapy for life.7 Chemotherapy conditioning can lead to the recovery of humoral immunity in this disease. However, conditioning for HSCT may cause severe life-threatening side effects, especially in early infancy.

CD3δ deficiency is a rare form of SCID (T−B+NK+).8 Although CD3-deficient patients who received HSCT with or without chemotherapy conditioning have been reported,9 it is not clear whether sufficient cellular and humoral immune reconstitution can be achieved after the HSCT without conditioning over long periods of time.

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Acknowledgements

This work was supported in part by a grant from Japan Agency for Medical Research and Development (15Aek0510006h0002). We thank Professor Tomohiro Morio, Tokyo Medical and Dental University, for providing us the method to analyze TRECs and KRECs. This study was approved by The Institutional Review Board of Kyushu University Hospital. Informed consent was obtained from all subjects.

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  1. Department of Pediatrics, Graduate School of Medical Sciences,

    H Takada, M Ishimura & T Hara

  2. Kyushu University, Fukuoka, Japan

    H Takada, M Ishimura & T Hara

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  1. H Takada
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Correspondence to H Takada.

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Takada, H., Ishimura, M. & Hara, T. Insufficient immune reconstitution after allogeneic cord blood transplantation without chemotherapy conditioning in patients with SCID caused by CD3δ deficiency. Bone Marrow Transplant 51, 1131–1133 (2016). https://doi.org/10.1038/bmt.2016.64

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