The study of early T-cell development in humans is challenging because of limited availability of thymic samples and the limitations of in vitro T-cell differentiation assays. We used an artificial thymic organoid (ATO) platform generated by aggregating a DLL4-expressing stromal cell line (MS5-hDLL4) with CD34+ cells isolated from bone marrow or mobilized peripheral blood to study T-cell development from CD34+ cells of patients carrying hematopoietic intrinsic or thymic defects that cause T-cell lymphopenia. We found that AK2 deficiency is associated with decreased cell viability and an early block in T-cell development. We observed a similar defect in a patient carrying a null IL2RG mutation. In contrast, CD34+ cells from a patient carrying a missense IL2RG mutation reached full T-cell maturation, although cell numbers were significantly lower than in controls. CD34+ cells from patients carrying RAG mutations were able to differentiate to CD4+CD8+ cells, but not to CD3+TCRαβ+ cells. Finally, normal T-cell differentiation was observed in a patient with complete DiGeorge syndrome, consistent with the extra-hematopoietic nature of the defect. The ATO system may help determine whether T-cell deficiency reflects hematopoietic or thymic intrinsic abnormalities and define the exact stage at which T-cell differentiation is blocked.

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Patients receiving allogeneic stem cell transplants (SCT) can remain acutely sick for many weeks and incur repeated diagnostic radiology procedures which may significantly increase radiation exposure. This retrospective cohort study was conducted to determine the cumulative radiation dose from diagnostic studies following SCT. Sixty-four consecutive patients with hematologic malignancies in a single tertiary care institution underwent total body irradiation-based myeloablative conditioning followed by 6/6 HLA-identical sibling allogeneic stem cell transplantation. The median follow up was three years. The cumulative effective dose in mSv from diagnostic radiologic studies in the peri-transplant period from day −30 to day +200 was calculated for each patient and its impact on overall survival and nonrelapse mortality was determined. The median cumulative radiation exposure from diagnostic radiologic procedures was 92 mSv (range 1.2–300), representing about 30× the normal annual background radiation for the population and 10% of the 1200cGy total body irradiation (TBI) dose used in conditioning. Sixty-five percent of the cumulative radiation exposure was delivered between day +1 and day 100 and CT scans contributed 88%. While radiation exposure from diagnostic procedures did not impact clinical outcomes the risk of second cancers in long term survivors is likely to be increased. Our results indicate that patients who are acutely ill for prolonged periods can receive clinically significant radiation doses during their hospital care. Our findings should prompt attempts to limit radiation exposure from diagnostic procedures in post-SCT recipients.