Retrospective Analysis of Donor Lymphocyte Infusions in Pediatric Patients With Mixed Chimerism After Hematopoietic Stem Cell Transplantation.
TL;DR
PreDLI is a safe and effective intervention in pediatric transplantation, particularly as repeated, escalating doses, while acknowledging that standardization remains challenging and outcome depends on center experience and indication.
Abstract
Background
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an essential therapy for several malignant and nonmalignant diseases, but relapse and graft loss remain the principal threats to its success. Routine monitoring of chimerism and minimal residual disease (MRD) enables early detection of imminent recurrence and guides pre-emptive donor lymphocyte infusion (preDLI), which aims to improve or stabilize mixed chimerism (MC) in nonmalignant indications and to exert a graft-versus-leukemia (GvL) effect in malignancies. Pediatric data remain limited and protocols heterogeneous, particularly for nonmalignant disorders. PROCEDURE This retrospective single-center study analyzed 56 pediatric patients who received preDLI at Tübingen Children's Hospital between 1998 and 2022 after HLA-matched or single-mismatched alloHSCT. Two primary endpoints were prespecified: the rate of MC stabilization or improvement after preDLI, and the cumulative incidence of de novo graft-versus-host disease (GvHD) attributable to preDLI. Competing risks methodology was applied for graft loss or relapse, non-relapse mortality, and GvHD. Analyses used R version 4.5.1 (α = 0.05).
Results
Cumulated doses ranged from 25 × 103 to 71 × 106 cells/kg, depending on HLA disparity and indication. PreDLI stabilized or improved MC in 65% of nonmalignant (20/31) and 60% of malignant (15/25) indications, averting graft loss without re-transplantation in most responders. Treatment was well tolerated; three patients (5.4%) developed de novo GvHD, all Grade I.
Conclusions
PreDLI is a safe and effective intervention in pediatric transplantation, particularly as repeated, escalating doses. We provide practical recommendations, while acknowledging that standardization remains challenging and outcome depends on center experience and indication.