We assessed late mortality in 1479 individuals who had survived 2 or more years after allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 25.9 years and median length of follow-up was 9.5 years. The conditional survival probability at 15 years from HCT was 80.2% (SE ‫؍‬ 1.9%) for those who were disease-free at entry into the cohort, and the relative mortality was 9.9 (95% confidence interval, 8.7-11.2). Relative mortality decreased with time from HCT, but remained significantly elevated at 15 years after HCT (standardized mortality ratio ‫؍‬ 2.2). Relapse of primary disease (29%) and chronic graft-versus-host disease (cGVHD: 22%) were the leading causes of premature death. Nonrelapserelated mortality was increased among patients older than 18 years at HCT (

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by somatic mutations in the blood of otherwise healthy adults. We hypothesized that in patients undergoing autologous stem-cell transplantation (ASCT) for lymphoma, CHIP at the time of ASCT would be associated with an increased risk of myelodysplastic syndrome and acute myeloid leukemia, collectively termed therapy-related myeloid neoplasm (TMN), and other adverse outcomes. MethodsWe performed whole-exome sequencing on pre-and post-ASCT samples from 12 patients who developed TMN after autologous transplantation for Hodgkin lymphoma or non-Hodgkin lymphoma and targeted sequencing on cryopreserved aliquots of autologous stem-cell products from 401 patients who underwent ASCT for non-Hodgkin lymphoma between 2003 and 2010. We assessed the effect of CHIP at the time of ASCT on subsequent outcomes, including TMN, cause-specific mortality, and overall survival. ResultsFor six of 12 patients in the exome sequencing cohort, mutations found in the TMN specimen were also detectable in the pre-ASCT specimen. In the targeted sequencing cohort, 120 patients (29.9%) had CHIP at the time of ASCT, which was associated with an increased rate of TMN (10-year cumulative incidence, 14.1% v 4.3% for those with and without CHIP, respectively; P = .002). Patients with CHIP had significantly inferior overall survival compared with those without CHIP (10-year overall survival, 30.4% v 60.9%, respectively; P , .001), including increased risk of death from TMN and cardiovascular disease. ConclusionIn patients undergoing ASCT for lymphoma, CHIP at the time of transplantation is associated with inferior survival and increased risk of TMN.

We assessed late mortality in 854 individuals who had survived 2 or more years after autologous hematopoietic cell transplantation (HCT) for hematologic malignancies. Median age at HCT was 36.5 years, and median length of follow-up was 7.6 years. Overall survival was 68.8% ؎ 1.8% at 10 years, and the cohort was at a 13-fold increased risk for late death (standardized mortality ratio