Published on March 12, 2025
Immunological Reconstitution and Infections After AlloHCT: Comparison of GvHD Prophylaxis Approaches
by Alex Kadhim
A retrospective cohort study, conducted by researchers at the University of Freiburg, provides a comprehensive analysis of immune reconstitution and infection outcomes following allogeneic hematopoietic cell transplantation (alloHCT). The researchers compared different graft-versus-host disease (GvHD) prophylaxis regimens: post-transplant cyclophosphamide (PTCY, n=68), anti-T lymphocyte globulin (ATLG) with matched unrelated donors (MUD/ATLG, n=280) and mismatched donors (MM/ATLG, n=54), and matched related donors without ATLG (MRD/NoATLG, n=97). While PTCY was associated with delayed early immune recovery and higher infection-related mortality within the first 100 days, it showed significantly better long-term immune reconstitution than ATLG-based regimens.
Data from 499 adult patients transplanted between 2015 and 2022 was analyzed, examining lymphocyte recovery, infection rates, and clinical outcomes. PTCY recipients experienced delayed engraftment of neutrophils (median time: 21 days) and lower NK cell and γδ T-cell counts in the early post-transplant period, which correlated with a higher rate of bloodstream infections (44%) in the first 100 days. In contrast, late immune recovery was significantly enhanced in the PTCY group, characterized by higher B-cell and CD4+ T-cell counts one year post-transplant. These metrics outperformed ATLG-based protocols and were comparable to the MRD/NoATLG group. CMV and EBV reactivation rates were also lower in PTCY and MUD/ATLG recipients compared to MM/ATLG, where lymphocyte reconstitution was impaired.
Importantly, PTCY patients exhibited no late infection-related deaths beyond day 100, contrasting with the MM/ATLG group, where 14% of patients succumbed to late infections. This demonstrates PTCY's capacity to facilitate robust adaptive immunity, including higher counts of naïve CD4+ and regulatory T cells, which were associated with superior long-term outcomes. Despite its early risks, PTCY combines the benefits of reducing GvHD with durable immune recovery, making it a promising strategy for optimizing outcomes in alloHCT patients. Future studies should explore strategies to mitigate early infection risks while leveraging its long-term benefits.
Reference
Meyer T, Maas-Bauer K, Wäsch R, et al. Immunological reconstitution and infections after alloHCT - a comparison between post-transplantation cyclophosphamide, ATLG and non-ATLG based GvHD prophylaxis. Bone Marrow Transplant. Published online November 19, 2024. http://doi.org/10.1038/s41409-024-02474-1
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