Impact of graft-versus-host disease prophylaxis on second primary malignancies after allogeneic haematopoietic stem cell transplantation

Second primary malignancies (SPMs) are a well-recognized late complication of allogeneic haematopoietic stem cell transplantation (HSCT). This study aims to evaluate the impact of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) combination on the incidence of SPMs, compared to other graft-versus-host disease (GvHD) prophylactic regimens. Among 1418 evaluable patients with a median follow-up of 6125 person-years, 138 patients developed an SPM. The cumulative incidence at 5 years was 10.6% (95% CI: 9-13). The use of ATG-PTCy was independently associated with a reduced risk of developing SPM (Hazard Ratio [HR], 0.65; p = 0.02), while older patient age (HR, 1.10; p = 0.03) and moderate-to-severe chronic GvHD (HR, 1.54; p = 0.02) were associated with an increased risk of SPM. Compared to the general population, HSCT recipients were 2.45 times more likely to develop a malignancy (p < 0.01). The 3-year overall survival from the time of SPM diagnosis was 69.8% (95% CI: 61-77) with haematological SPM independently associated with inferior survival (HR: 2.40; 95% CI: 1.3-4.5; p < 0.01). Fifteen patients (11%) developed more than one SPM. In conclusion, ATG-PTCy appears to reduce the risk of SPM post-HSCT. Active surveillance and screening for SPMs in transplant survivors are of paramount importance to ensure favourable outcomes.