The 67th ASH Annual Meeting and Exposition delivered powerful advances across hematopoietic cell transplantation and cellular therapy, signaling a future that is safer, more precise and increasingly engineered. Below, Dr Esra Gülderen (Helsinki University, Finland and Co-chair of the EBMT Trainee Committee) breaks down seven major abstracts from ASH25, highlighting their take-aways and considering their potential relevance for clinical practice.
“These ASH25 data highlight the potential of integrating engineering and immunology to improve transplant safety, enhance cellular therapies and deepen clinical responses”
In allogeneic transplantation, Villar-Prados et al. presented early phase I results of Orca-T, a regulatory T-cell–engineered graft following reduced-intensity conditioning. The study met all feasibility and safety endpoints, with robust engraftment, strong donor chimerism and strikingly low rates of acute and chronic graft versus host disease (GVHD) while preserving graft-versus-leukaemia activity. These results firmly support upcoming multicentre trials.
In acute myeloid leukaemia (AML), Maffini et al. (EBMT Acute Leukaemia Working Party) addressed one of the field’s most debated questions: optimal myeloablative conditioning for adolescents and young adults. Their large registry analysis showed that total body irradiation (TBI)-free high-dose regimens, particularly thiotepa, busulfan, fludarabine (TBF) and busulfan, fludarabine (Bu-Flu), deliver superior survival and lower toxicity, reflecting both regimen choice and modern supportive care.
Cellular engineering took center stage with Coutinho de Oliveira et al., who used patient-informed CRISPR screening to identify gene targets that enhance CAR-T proliferation, persistence and antitumour efficacy. Disruption of genes such as CARD8 and SRCAP significantly improved tumor clearance and survival in vivo, offering a roadmap for next-generation armoured CAR-T design.
For central nervous system (CNS) leukaemia, Leontari et al. demonstrated that CAR-iNKT cells outperform CAR-T cells in leptomeningeal disease, driven by superior VLA-4–mediated endothelial adhesion and CNS retention, a finding with broad implications for CNS-involved hematologic malignancies.
In chronic GVHD, Salhotra et al. reported the first-in-human use of allogeneic CD6-CAR Tregs, showing excellent tolerability, no cytokine release syndrome, no immune effector cell-associated neurotoxicity syndrome and no need for salvage immunosuppression, a major step toward immune re-education rather than immune suppression.
Transplant strategy was further refined by Ye et al., who showed that in MRD-positive AML, haploidentical transplantation outperformed matched sibling donors in leukaemia-free and GVHD-free relapse-free survival, driven by superior relapse control.
Chiesa et al. showcased one of the most exciting cellular therapy platforms to date: universal base-edited CAR7 T cells for relapsed/refractory T-cell acute lymphoblastic leukaemia. Despite heavily pretreated disease, 82% achieved MRD-negative remission enabling curative allogeneic stem cell transplant, with 63% remaining in durable remission up to three years post-transplant.
Disclosure: Esra Gülderen has no financial or non-financial conflicts of interest to declare in relation to this article.
Cite: Inside ASH25: Breakthroughs redefining transplantation and cell therapy. December 11th, 2025
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