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Abstract: Long-term morbidity after hematopoietic cell transplantation (HCT) is unknown. The risk of physical and psychological health in 324 patients who had survived 10 or more years after HCT and a sibling comparison group (n = 309) was evaluated. Using the Common Terminology Criteria for Adverse Events, the 15-year cumulative incidence of severe/life-threatening/fatal conditions was 41% (95% confidence interval, 34% to 48%). HCT survivors were 5.7 times as likely to develop a severe/life-threatening condition (P < .001) and 2.7 times as likely to report somatic distress (P < .001) compared with siblings. Compared with allogeneic HCT recipients with no chronic graft-versus-host disease (GVHD), those with active chronic GVHD were at a 1.8-fold higher risk of severe/life-threatening health conditions (P = .006) and a 4.5-fold higher risk of somatic distress (P = .04); allogeneic HCT recipients with resolved chronic GVHD were not at increased risk of morbidity compared with those with no chronic GVHD. Only 27% of the HCT survivors returned to the transplantation center for their cancer-related care. The burden of long-term physical and emotional morbidity borne by survivors remains substantial, even beyond 10 years after HCT; however, specialized health care is underused. Patients, families, and healthcare providers need to be made aware of the high burden, so they can plan for post-HCT care, even many years after HCT. [Copyright &y& Elsevier]

Long-term survival after hematopoietic cell transplantation (HCT) is now an expected outcome. The growing population of survivors is at risk of developing treatment-related complications, including cardiovascular disease (CVD). A nested case-controlled design was used to identify clinical and treatment-related risk factors for development of late (1+ years after HCT) CVD. Cases were identified from a cohort of 1+-year survivors who underwent transplantation at City of Hope between 1977 and 2006. Controls (HCT survivors without CVD) were matched on age, year of HCT, type of HCT, and duration of follow-up. Sixty-three patients with late CVD were identified, 44 (69.8%) with a coronary artery event and 19 (30.2%) with a cerebrovascular event. Median age at HCT was 49.0 years. Median age at onset of late CVD was 54.0 years; 66.7% of the affected patients had undergone autologous HCT. Multivariate logistic regression analysis showed that the presence of multiple cardiovascular risk factors (2 or more of the following: obesity, dyslipidemia, hypertension, and diabetes) after HCT was associated with a 5.2-fold increased risk of late CVD (P < .01), and that pre-HCT chest radiation exposure was associated with a 9.5-fold greater risk of coronary artery disease (P = .03). Pre-HCT exposure to chest radiation and the presence of comorbidities were primarily responsible for the risk associated with late CVD after HCT. These data form the basis for developing predictive models for identifying high-risk individuals for targeted surveillance and aggressive management of comorbidities. [Copyright &y& Elsevier]

Abstract: Recent studies demonstrate an increased risk of second primary malignancies (SPMs) in patients with multiple myeloma (MM) receiving maintenance lenalidomide after autologous stem cell transplantation (ASCT). We explored the possibility of other risk factors driving post-ASCT SPMs in patients with MM through analysis of our large transplantation database in conjunction with our Long-Term Follow-Up Program. We conducted a retrospective cohort study of 841 consecutive patients with MM who underwent ASCT at City of Hope between 1989 and 2009, as well as a nested case-control analysis evaluating the role of all therapeutic exposures before, during, and after ASCT. Median duration of follow-up for the entire cohort was 3.4 years (range, 0.3-19.9 years). Sixty cases with a total of 70 SPMs were identified. The overall cumulative incidence of SPMs was 7.4% at 5 years and 15.9% at 10 years when nonmelanoma skin cancers (NMSCs) were included and 5.3% at 5 years and 11.2% at 10 years when NMSCs were excluded. Multivariate analysis of the entire cohort revealed associations of both older age (≥55 years; relative risk, 2.3; P < .004) and race (non-Hispanic white; relative risk, 2.4; P = .01) with an increased risk of SPM. Furthermore, thalidomide exposure demonstrated a trend toward increased risk (odds ratio, 3.5; P = .15); however, an insufficient number of patients were treated with lenalidomide to allow us to accurately assess the risk of this agent. Exclusion of NMSCs retained the association with these variables but was accompanied by loss of statistical significance. This large single-institution analysis identified associations between race and older age and increased risk of developing SPM. The trend toward increased risk with thalidomide exposure suggests a class effect from immunomodulatory drugs that might not be restricted to lenalidomide. [Copyright &y& Elsevier]

Abstract: We determined the prevalence of self-reported late-effects in survivors of autologous hematopoietic cell transplantation (HCT) for Hodgkin lymphoma (HL, n = 92) and non-Hodgkin lymphoma (NHL, n = 184) using a 255-item questionnaire and compared them to 319 sibling controls in the Bone Marrow Transplant Survivor Study. Median age at HCT was 39 years (range: 13-69) and median posttransplant follow-up was 6 years (range: 2-17). Median age at survey was 46 years (range: 21-73) for survivors and 44 years (range: 19-79) for siblings. Compared to siblings, HCT survivors reported a significantly higher frequency of cataracts, dry mouth, hypothyroidism, bone impairments (osteoporosis and avascular necrosis), congestive heart failure, exercise-induced shortness of breath, neurosensory impairments, inability to attend work or school, and poor overall health. Compared to those receiving no total-body irradiation (TBI), patients treated with TBI-based conditioning had higher risks of cataracts (odds-ratio [OR] 4.9, 95% confidence interval [CI] 1.5-15.5) and dry mouth (OR 3.4, 95% CI 1.1-10.4). Females had a greater likelihood of reporting osteoporosis (OR 8.7, 95% CI: 1.8-41.7), congestive heart failure (OR 4.3, 95% CI 1.1-17.2), and abnormal balance, tremor, or weakness (OR 2.4, 95% CI 1.0-5.5). HL and NHL survivors of autologous HCT have a high prevalence of long-term health-related complications and require continued monitoring for late effects of transplantation. [Copyright &y& Elsevier]