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Unconditioned unrelated donor bone marrow transplantation for IL7Rα- and Artemis-deficient SCID

Bone Marrow Transplantation volume 52, pages 1036–1038 (2017)Cite this article

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SCID is a heterogeneous group of genetic disorders resulting in severe T- and B-cell immunodeficiency with susceptibility to life-threatening infections.1, 2 Because most patients lack the optimal donor for hematopoietic cell transplantation (HCT), an HLA-matched sibling donor (MSD),1 many SCID HCTs employ alternate stem cell sources: T-cell-depleted mismatched related donors (MMRDs); closely-HLA-matched unrelated adult donors (URDs); or unrelated umbilical cord blood (UCB). Because SCID-affected recipients are unable to reject HLA-matched allogeneic cells, MSD bone marrow transplantations (BMTs) are typically done without conditioning.1,2 This principle also applies to MMRD HCT with the exception that natural killer (NK) cells in certain SCID genotypes may resist donor engraftment.3, 4 However, most URD and UCB HCTs have been performed using alkylator-chemotherapy conditioning, reflecting experience with HCT for non-SCID conditions.1,5

In a previously reported retrospective multicenter study, comparing unconditioned URD to MSD HCT for SCID, despite similar T-cell engraftment, 5-year survival was inferior in URD recipients.6 However, pre-HCT serotherapy in the URD group may have improved survival. Compared to MSD recipients, the URD group also had higher rates of acute GvHD. The genotypes of the unconditioned URD group were IL2RG (n=27) and ADA (n=7), both associated with lack of NK cells (NK−); RAG2 (n=1) and DCLRE1C/Artemis (n=1), both NK+; and unknown SCID genotypes (n=7), with variable NK cells. The Artemis SCID patient engrafted, but died on day +145 from respiratory syncytial virus (RSV) and chronic GvHD. Thus, it remains unclear whether unconditioned URD HCT could provide T-cell reconstitution for NK+ SCID if infections and GvHD could be controlled. We report here successful unconditioned URD HCTs in NK+ IL7R and Artemis SCID.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, Benioff Children’s Hospital, University of California, San Francisco, San Francisco, CA, USA

    C C Dvorak, K Patel, J M Puck, J Wahlstrom, M J Dorsey, J Facchino & M J Cowan

  2. Blood and Marrow Transplantation Division, The Center for Cancer & Blood Disorders, Phoenix Children’s Hospital, Phoenix, AZ, USA

    R Adams

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  1. C C Dvorak
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  2. K Patel
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  3. J M Puck
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  6. R Adams
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  7. J Facchino
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  8. M J Cowan
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Correspondence to C C Dvorak.

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Dvorak, C., Patel, K., Puck, J. et al. Unconditioned unrelated donor bone marrow transplantation for IL7Rα- and Artemis-deficient SCID. Bone Marrow Transplant 52, 1036–1038 (2017). https://doi.org/10.1038/bmt.2017.74

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