Stem cell transplantation in the era of post-transplant cyclophosphamide (PTCy): Donor biology, immunosenescence, and transplant immunology

The field of allogeneic hematopoietic stem cell transplantation (HSCT) has been significantly transformed by the use of post-transplant cyclophosphamide (PTCy) as an effective prophylaxis for graft-versus-host disease (GVHD). This innovation has widened the pool of potential donors by enabling safer mismatched and haploidentical transplant procedures, thereby improving patient access to life-saving treatments. However, despite these advances, key questions remain regarding the interactions between PTCy, intrinsic donor attributes such as biological age and telomere dynamics, and the broader phenomenon of immunosenescence. Contemporary studies highlight that donor characteristics, including age-related immune alterations and genetic differences at the human leukocyte antigen (HLA) level, play a pivotal role in shaping early and long-term immune outcomes, yet the underlying mechanisms and clinical implications are not fully elucidated.

This Research Topic aims to deepen our understanding of how donor biology intersects with PTCy-based transplantation to influence immune recovery, alloreactivity, and patient outcomes. Specifically, it seeks to explore the effects of donor biological age, telomere attrition, and the complexity of HLA mismatches on graft cellular composition and the diversity of the T-cell repertoire. Furthermore, by addressing the dynamics of immune reconstitution across lymphoid and myeloid lineages, and examining both allogeneic and anti-tumor immune responses, this topic strives to unravel how donor-related factors affect key clinical endpoints such as GVHD, relapse rates, infection susceptibility, and overall transplant success. These investigations are crucial for developing predictive biomarkers and tailored therapeutic strategies that harness the full potential of PTCy in diverse donor settings.

To gather further insights in this evolving landscape, the research will focus on the interplay between donor factors and immune function in PTCy-based HSCT, while excluding unrelated transplantation protocols or therapies. We welcome articles addressing, but not limited to, the following themes:

The influence of donor biological age and telomere length on graft composition and engraftment outcomes
• HLA mismatching and non-HLA immunogenetic factors in shaping immune reconstitution
• T-cell repertoire diversity, thymic function, and immunosenescence in post-PTCy transplantation
• Mechanistic dissection of regulatory and alloreactive T-cell populations in the context of donor characteristics
• Integration of multi-omics, immune profiling, and computational modeling to predict clinical endpoints such as GVHD, relapse, and infection risk

We encourage submissions of original research, comprehensive reviews, and translational studies that can bridge basic immunology with clinical innovation in the era of PTCy-facilitated allogeneic transplantation.



Dr. Philip Imus received grant funding from Janssen to perform clinical trials. All other Topic Editors declare no competing interests with regard to the Research Topic subject.