PreDLI stabilizes or improves chimerism in 60 to 65% of pediatric transplant recipients
The study reports a retrospective single-center analysis of 56 pediatric patients who received preemptive donor lymphocyte infusions following allogeneic hematopoietic stem cell transplantation. Routine chimerism and minimal residual disease monitoring enabled early intervention, which stabilized or improved mixed chimerism in 65% of nonmalignant and 60% of malignant cases while averting graft loss without requiring re-transplantation. Treatment was well tolerated, with only 5.4% of patients developing de novo grade I graft-versus-host disease. The findings provide practical guidance for molecular monitoring protocols and preDLI dosing strategies in pediatric transplant care, though authors note that standardization remains challenging.
The original study
Retrospective Analysis of Donor Lymphocyte Infusions in Pediatric Patients With Mixed Chimerism After Hematopoietic Stem Cell Transplantation.
- Authors
- Junk C, Michaelis S, Döring M, Eichholz T, Holzer U, Ebinger M, et al.
- Journal
- Pediatric blood & cancer
- Type
- Journal Article
- PMID
- 42775471
Original 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.