Thesis defense Anniek Stuut

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Allogeneic stem cell transplantation can cure patients with blood cancers and severe bone marrow disorders. Donor stem cells rebuild the patient’s immune system, which can eliminate residual malignant cells, but may also cause major complications. A key complication is graft-versus-host disease (GVHD), where donor immune cells attack healthy tissues. Infections are another challenge, including cytomegalovirus (CMV) reactivation. CMV reactivation can lead to CMV disease and intensive antiviral therapy, and it can shape immune recovery after transplantation. Importantly, CMV is not always purely harmful: CMV-driven immune activation may also generate T cells that contribute to anti-leukaemic or anti-tumour effects.

At University Medical Center Utrecht, we use a platform that removes αβ T cells from the graft before infusion. This thesis evaluated how this approach affects clinical outcomes and immune reconstitution. αβ T-cell–depleted transplantation was associated with low rates of acute and chronic GVHD and improved GVHD-free, relapse-free survival (GRFS), but CMV-seropositive patients experienced CMV reactivation more often, indicating a shifted post-transplant risk profile.

We also assessed graft cryopreservation. Freezing the graft did not adversely affect survival or GVHD, despite lower stem cell recovery after thawing. This is an important finding when logistics are constrained (e.g., during a pandemic). In myelofibrosis, a disease with a high inflammatory burden, outcomes improved when ruxolitinib was continued around transplantation. Finally, advanced immune profiling showed that both CMV reactivation and the transplant platform influence how T cells expand, persist, and diversify over time. Together, these findings support more personalized transplant strategies that balance GVHD prevention, infection risk, and immune recovery.