Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial.

BACKGROUND AIMS: Delayed immune reconstitution is a major challenge after matched unrelated donor (MUD) stem cell transplant (SCT). In this randomized phase 2 multi-center trial, Adoptive Immunotherapy with CD25/71 allodepleted donor T cells to improve immunity after unrelated donor stem cell transplant (NCT01827579), the authors tested whether allodepleted donor T cells (ADTs) can safely be used to improve immune reconstitution after alemtuzumab-based MUD SCT for hematological malignancies. METHODS: Patients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm. RESULTS: The authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively. CONCLUSIONS: These data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion.

Mosaic patch patterns in chimeric and transgenic mice suggest that directional growth in the adrenal cortex begins in the perinatal period.

Staining for beta-galactosidase (beta-gal) reporter activity in adrenal glands from adult, fetal and neonatal 21-OH/LacZ transgenic mice revealed mosaic patch patterns that were qualitatively similar to those seen in LacZ <--> wild-type mouse chimeras, at similar developmental stages. This suggests that, as in chimeras, the transgenic patch pattern may reflect cell lineage relationships. Consequently, 21-OH/LacZ transgenic mice could be useful as a simpler alternative to chimeras for the analysis of clonal growth and cell mixing during adrenocortical organogenesis. Embryonic day 16.5 (E16.5) adrenal cortices of 21-OH/LacZ transgenic mice displayed a punctate patch pattern, but by E18.5 "stripes" appeared to be emerging and were clearly visible by the day of birth (P0) and three days later (P3), consistent with the adult mosaic striped pattern. This suggests that adrenocortical organogenesis involves an initial period of randomly oriented clonal growth, followed by directional growth which begins in the perinatal period.