Continuing increased risk of oral/esophageal cancer after allogeneic hematopoietic stem cell transplantation in adults in association with chronic graft-versus-host disease

Background: The number of long-term survivors after hematopoietic stem cell transplantation (HSCT) showed steady increase in the past two decades. Second malignancies after HSCT are a devastating late complication. We analyzed the incidence of, risk compared with that in the general population, and risk factors for secondary solid cancers. Patients and methods: Patients were 17 545 adult recipients of a first allogeneic stem cell transplantation between 1990 and 2007 in Japan. Risks of developing secondary solid tumors were compared with general population by using standard incidence ratios (SIRs). Results: Two-hundred sixty-nine secondary solid cancers were identified. The cumulative incidence was 0.7% [95% confidence interval (CI), 0.6%-0.9%] at 5 years and 1.7% (95% CI, 1.4%-1.9%) at 10 years after transplant. The risk was significantly higher than that in the general population (SIR = 1.8, 95% CI, 1.5-2.0). Risk was higher for oral cancer (SIR = 15.7, 95% CI, 12.1-20.1), esophageal cancer (SIR = 8.5, 95% CI, 6.1-11.5), colon cancer (SIR = 1.9, 95% CI, 1.2-2.7), skin cancer (SIR = 7.2, 95% CI, 3.9-12.4), and brain/nervous system cancer (SIR = 4.1, 95% CI, 1.6-8.4). The risk of developing oral, esophageal, or skin cancer was higher at all times after 1-year post-transplant. Extensive-type chronic graft-versus-host disease (GVHD) was a significant risk factor for the development of all solid tumors (RR = 1.8, P < 0.001), as well as for oral (RR = 2.9, P < 0.001) and esophageal (RR = 5.3, P < 0.001) cancers. Limited-type chronic GVHD was an independent risk factor for skin cancers (RR = 5.8, P = 0.016). Conclusion: Recipients of allogeneic HSCT had a significantly higher ̃2-fold risk of developing secondary solid cancers than the general population. Lifelong screening for high-risk organ sites, especially oral or esophageal cancers, is important for recipients with active, or a history of, chronic GVHD.