Comment on "Impact of graft‐versus‐host disease prophylaxis on second primary malignancies after allogeneic haematopoietic stem cell transplantation”
Br J Haematol. 2025 Jul. Desai N, et al.
Comment by Gonzalo Daniel Bentolila, Medical Faculty, HSCT Unit, Fundaleu (Fundación contra la Leucemia), Buenos Aires, Argentina.
Desai et al. conducted a retrospective study to assess whether different graft-versus-host disease (GvHD) prophylaxis regimens influence the risk of second primary malignancies (SPMs) after allogeneic hematopoietic stem cell transplantation (HSCT). This study, conducted between 2010–2022, included 1418 evaluable patients with a total follow-up of 6125 person-years. The patients were divided into two groups: those receiving anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy)–calcineurin inhibitor (CNI) prophylaxis (n=761) and those receiving other regimens (n=657).
The cumulative incidence of SPM at 5 years was 10.6% (95% CI: 9–13) overall, 9% in the ATG–PTCy–CNI group, and 12% in the other regimens group. Notably, multivariate analysis showed a statistically significant protective effect of ATG–PTCy–CNI prophylaxis (HR 0.65, p=0.02). Key risk factors identified for SPM development included older patient age (HR 1.10, p=0.03) and moderate-to-severe chronic GvHD (HR 1.54, p=0.02).
Comparison with the general population revealed an elevated annual incidence rate of malignancies (SIR 2.45, 95% CI: 1.95–3.03, p<0.01). Skin cancers (41%), post-transplant lymphoproliferative disorders (18%), solid organ tumors, and hematological malignancies were among the most frequent SPM types. Patients with hematological SPMs had significantly worse survival outcomes, with a 3-year overall survival of 49% compared to 65.2% in solid organ malignancies (HR 2.4, p=0.006).
The authors emphasize the critical role of chronic GvHD in SPM pathogenesis, mediated by prolonged immunosuppression and chronic epithelial damage. The ATG–PTCy–CNI regimen's demonstrated ability to reduce chronic GvHD incidence suggests a plausible mechanism for its protective effect against SPM. The study highlights the need for long-term follow-up and prospective validation.
Comment:
This work reframes GvHD prophylaxis as more than immune modulation—it emerges as a modifiable risk factor for late malignancy, linking early intervention to long-term outcomes.