Escalated dose donor lymphocyte infusion treatment in patients with primary immune deficiencies after HSCT with reduced-intensity conditioning regimen

Objective/Background:
Mixed chimerism is a major concern after allogenic hematopoietic stem cell transplantation (HSCT) using a reduced-intensity conditioning (RIC) regimen in primary immunodeficiencies (PIDs). A donor lymphocyte infusion (DLI) escalating dose regimen has been developed with the aim of reducing toxicity while preserving efficacy. However, the graft-versus-host disease (GvHD) development remains the most common and adverse effect of DLI and continues to be a limiting factor in its application, especially nonmalignant diseases such as PIDs. We prospectively evaluated PID patients after HSCT using RIC in Children s Medical Center, who were candidates for an escalating dose of DLI for MC from 2016 to 2018.


Methods:
With the median follow-up of 16.4 months, 12 patients (nine males and three females) with a median age of 3.72 years received DLI. The median number of DLI was 3.2 (range, 1–5), the maximum and total dose of DLIs administered per patient were 3.6 × 107 (range, 1–5) cells/kg CD3+ and 9.3 × 107 (range, 1–15) cells/kg CD3+ cells, respectively.


Results:
Median donor chimerism at baseline before the DLIs was 41% (range, 11–73%), patients received DLIs at a median of 105 (range, 37–230) days and 52 (range, 3–168) days after the HSCT and onset of the MC, respectively. At the final assessment, six (54.5%) patients improved after DLIs at a median of 47.3 days.


Conclusion:
PID patients may benefit from DLI with an escalating dose regimen, but the GvHD development remains a concern during the DLI, and the optimum dose and frequency must be standardized.