Effect of Donor Lymphocyte Infusion From Two Types of Donors on Mixed Chimerism With Secondary Graft Failure After Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Mixed chimerism (MC) and secondary graft failure (SGF) with recipient- or donor-type chimerism is a major obstacle in allogeneic hematopoietic stem cell transplantation (HSCT). Donor lymphocyte infusion (DLI) can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions after HSCT. This study aimed to analyze the efficacy and immune mechanism of DLI from the original and alternative donor for patients of mixed donor chimerism with SGF. The alternative donor refers to the candidate relative donor who did not initially provide stem cells and includes HLA-matched sibling donor or HLA-haploidentical donor. We conducted a retrospective study of 246 patients with a median age of 37 (9-58) years who had regularly detected MC, complete donor chimera (CC), and regulatory T cells (Treg). The median diagnosis time of SGF was 69 (39-141) days after transplantation. Sixteen patients with SGF received DLI from the alternative donor, including 3 patients who chose DLI from the original donor with no initial response and 13 patients who directly chose DLI from the alternative donor. Sixteen patients with SGF existed mixed chimerism synchronously and the rate calculated overall chimerism of MC was 63% (range 42%-85%) after transplantation. The proportion of Treg decreased significantly in SGF patients from a median of 2.66% ± 0.80% to 0.93% ± 0.57% at a time point after transplantation (P = .02). The DLI of the alternative donor in 14 patients achieved complete response and MC gradually convert to CC state, simultaneously there was significant increase in the Treg fraction (SGF versus complete response: 0.93% ± 0.57% versus 3.61% ± 0.82% [P = .01]). For the clinical nonresponders from 2 types of donors, there was no significant change in MC and Treg cells. The OS and disease-free survival at 2 years after DLI were 69.7% ± 3.19% and 61.3% ± 4.80%, respectively. DLI from the alternative donor may be an effective treatment for MC with SGF, and the mechanism is closely related to the activation of Treg cells level.

Keywords: Donor lymphocyte infusion; Mixed chimerism; Regulatory T cells; Secondary graft failure.