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

The aim of this study was to understand the impact of chronic graft-versus-host disease (cGVHD) on the overall health status of hematopoietic cell transplantation (HCT) survivors. Subjects included 584 individuals who had undergone allogeneic HCT between 1976 and 1999, survived 2 or more years, and completed a 255-item health questionnaire. Global assessment of health status was facilitated by measurement of 6 health status domains: general health, mental health, functional impairment, activity limitation, pain, and anxiety/fear. Information regarding diagnosis of cGVHD was abstracted from medical records, and presence of active cGVHD in the preceding 12 months was self-reported. The incidence of cGVHD in participants was 54%, of whom 46% reported active cGVHD. In multivariable analyses, subjects with active cGVHD were more likely to report adverse general health, mental health, functional impairments, activity limitation, and pain than were those with no history of cGVHD. However, health status did not differ between those with resolved cGVHD and those who never had cGVHD. We conclude that active cGVHD has a significant impact on many aspects of the overall health status of HCT survivors and that, most importantly, those successfully treated for cGVHD do not appear to have long-term impairments. (Blood. 2006;108: 2867-2873)

Hematopoietic cell transplantation (HCT

Long-term survival is now an expected outcome after hematopoietic cell transplantation (HCT).

HSCT is being increasingly offered as a curative option for children with hematologic malignancies. Although survival has improved, the long-term morbidity ascribed to the HSCT procedure is not known. We compared the risk of chronic health conditions and adverse health among children with cancer treated with HSCT with survivors treated conventionally, as well as with sibling controls. HSCT survivors were drawn from BMTSS (N ‫؍‬ 145), whereas conventionally treated survivors (N ‫؍‬ 7207) and siblings (N ‫؍‬ 4020) were drawn from CCSS. Selfreported chronic conditions were graded with CTCAEv3.0. Fifty-nine percent of HSCT survivors reported > 2 conditions, and 25.5% reported severe/life-threatening conditions. HSCT survivors were more likely than sibling controls to have severe/ life-threatening (relative risk [RR] ‫؍‬ 8.1, P < .01) and 2 or more (RR ‫؍‬ 5.7, P < .01) conditions, as well as functional impairment (RR ‫؍‬ 7.7, P < .01) and activity limitation (RR ‫؍‬ 6.3, P < .01). More importantly, compared with CCSS survivors, BMTSS survivors demonstrated significantly elevated risks (severe/lifethreatening conditions: RR ‫؍‬ 3.9, P < .01; multiple conditions: RR ‫؍‬ 2.6, P < .01; functional impairment: RR ‫؍‬ 3.5, P < .01; activity limitation: RR ‫؍‬ 5.8, P < .01). Unrelated donor HSCT recipients were at greatest risk. Childhood HSCT survivors carry a significantly greater burden of morbidity not only compared with noncancer populations but also compared with conventionally treated cancer patients, providing evidence for close monitoring of this high-risk population. (Blood. 2011;118(5):1413-1420)

No abstract