GVHD prophylaxis and incidence in contemporary alloHSCT: a large real-world GETH/TC analysis

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes. The increasing use of post-transplant cyclophosphamide (PTCy) and antithymocyte globulin (ATG) has expanded beyond haploidentical transplantation to matched related (MRD) and unrelated donor (MUD) settings, although real-world GVHD incidence in this context is not well characterized. We performed a nationwide retrospective study including 1544 alloHSCTs conducted in Spain between 2018 and 2020. PTCy-based prophylaxis was used in 65.6% of transplants, being almost universal in haploidentical procedures (96.9%) and predominant in mismatched donors (72.4%), with notable use in MRD (43.5%) and MUD (56.8%). The cumulative incidence of grade II-IV acute GVHD at day +100 and 1 year was 28.4% and 30.7%, respectively, while grade III-IV occurred in 6.9% and 8.0%. Despite the prevalent use of peripheral blood stem cells, chronic GVHD at 2 years was 36.7%, with 23.5% moderate-to-severe. Acute GVHD was strongly associated with inferior survival (HR 2.40; P < 0.001), particularly grade III-IV disease (HR 4.34; P < 0.001). This large nationwide real-world study highlights the shift in GVHD prophylaxis in modern alloHSCT and underscores the need to define new studies based on this evolving landscape.