Subsequent cancers (SC) are a significant cause of morbidity and mortality in long-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic graft-versus-host disease (cGVHD) and treatment-related immunosuppression have been recognized as risk factors for SC.
This study sought to investigate the incidence and risk factors for SC in patients with established cGVHD, assessed separately for onset of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)-categorized into non-melanoma skin cancers (NMSC)-and all cancers other than NMSC.
Two-hundred-and-four patients were enrolled in the prospective cross-sectional cGVHD Natural History Study and underwent comprehensive clinical evaluation. Patients were followed up with annual survey. Cumulative incidence of NMSC and cancers other than NMSC with competing risks was estimated separately, and transplant- and cGVHD-related factors were assessed for association with outcomes using Grey’s test and multivariable Cox models. Time for all analyses began at two years post-evaluation to restrict analyses to patients who were presumed to not have had SC present at evaluation.
Nineteen patients were diagnosed with NMSC and 19 with cancers other than NMSC with 10-year cumulative incidences of 15.5% (95% CI: 9.0-27.6) and 13.8% (95% CI: 8.2-20.8), respectively. Age at transplant (HR=1.94; 95% CI: 1.23-3.06) and higher CRP at evaluation (HR=9.49; 95% CI: 1.26-71.58) were jointly associated with NMSC, while and gastrointestinal cGVHD at evaluation (HR=0.26, 95% CI: 0.09-0.78) was associated with reduced risk of NMSC. T-cell depletion at transplant (HR=3.09; 95% CI: 1.17-8.20), lymphoma as transplant indication (HR=3.96; 95% CI: 1.56-10.05), and oral cGVHD severity at evaluation (HR=4.36; 95% CI: 1.52-12.46) were jointly associated with cancers other than NMSC.
This study estimates incidence of SC in a population of severely-affected cGVHD patients and identifies correlations with subsequent development of SC. These factors seem to be different for NMSC and cancers other than NMSC. Further longitudinal investigations accounting for dynamic and cumulative processes are needed to improve understanding and management of SC.

Copyright © 2021. Published by Elsevier Inc.