Risk Factors for Second Malignancies after Transplantation Differ between Allogeneic and Autologous Transplantation.

Survivors of hematopoietic stem cell transplantation (HSCT) are at risk for second malignant neoplasms (SMN). We undertook this analysis to ascertain whether risk of SMN was comparable in survivors of allogeneic and autologous transplantation. Among 8662 transplant recipients treated at the Fred Hutchinson Cancer Research Center between November 1969 and April 2004, who survived at least 100 days post transplant, there were 1743 autologous and 6919 allogeneic HSCT recipients. Within this cohort, there were 56 SMNs among the autologous and 224 among the allogeneic recipients. Cumulative incidence of SMN at 10 years post-HSCT was 2.6% in the allogeneic and 4.2% in the autologous HSCT survivors. A multivariate Cox regression model adjusted for current age, TBI, gender and length of follow-up was fit and the hazard ratio (HR) for SMN for the allogeneic transplant survivors was 0.7 (95% confidence interval {CI} 0.5, 1.0) compared to the autologous transplant survivors (reference group), suggesting that the adjusted hazard of SMN is higher for autologous than for allogeneic HSCT recipients. Risk factors differed between the two groups. For survivors of autologous transplantation, in multivariate Cox regression models, only age > 18 years at transplant was associated with decreased risk of SMN (<18 years HR = 1.0; 18–39 years HR = 0.04; 40+ years HR = 0.004). Use of total body irradiation (TBI) was not significantly associated with risk among the autologous HSCT recipients. For allogeneic transplant survivors, increased risk of SMN was associated with TBI and the effect of TBI was stronger for younger (<18 years at HSCT: HR = 4.6; 95% CI 1.6, 13.5) than for older (≥18 years; HR = 1.5; 95% CI 1.0, 2.3) HSCT recipients (interaction p = 0.04) in multivariate Cox regression models. Risk was also increased after acute graft versus host disease (HR = 1.4; 95% CI 1.0, 1.9) and with ongoing follow-up time, with HRs of 1.7 (95% CI 1.1, 2.5) at 10 – 14 years, 2.2 (95% CI 1.3, 3.7) at 15–19 years and 2.6 (95% CI 1.2, 5.4) at 20+ years of follow-up. Unrelated HSCT also increased risk of SMN (HR = 1.4; 95% CI 1.0, 2.0). In adjusted analyses, risk of SMN thus appears slightly lower in allogeneic versus autologous transplant survivors, and risk factors appear different between the two groups. Attention should focus on modifiable risk factors in both groups. Particularly in autologous transplant survivors, the relative contribution of pre-transplant exposures must be established.