Secondary Malignancies in Patients after Allogeneic Hematopoietic Cell Transplantation at Triple the Incidence of Malignancies in Their Family Donors

Abstract

The primary end point of this retrospective study was to determine the incidence, risk factors and clinical outcome of secondary malignancies in 951 patients who were given an allogeneic Hemopoietic Cell Transplantation (HCT) and to compare them with the incidence of malignancy observed in the cohort of 761 stem cell family donors. With a median follow-up of 20 years, 74 HCT recipients (40 males) developed SM at a median of 16.09 years since transplant and at a median age of 47 years. The 35-yr cumulative incidence of SM was 17.0% (95% confidence interval, 12.8-21.6%). In univariate analysis, factors associated with increased incidence of SM were cumulative (limited and extensive) chronic graft-versus-host disease (cGvHD) and duration of cumulative cGvHD >24 months. By multivariate analysis, cumulative cGvHD was the only independent risk factor for SM. Patients with cGvHD had 2.85x higher risk as compared to patients without cGvHD (P<0.001). With a median follow-up of 18 years, 13 family donors (7 males) out of 761 developed malignancy at a median of 15.04 years since stem cell donation and at a median age of 55 years. As compared to the cumulative incidence of SM observed in the cohort of transplant recipients, the cumulative incidence of malignancy in family donors at 35 years since stem cell donation was statistically lower [5.8% vs 17.0% (P=0.001)]. This study demonstrates that HCT recipients have a significantly higher incidence of developing post-transplant malignancy as compared to family donors and that cGvHD is a strong risk factor for SM development.