Jennifer Berano Teh

Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS)

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. Self-reported 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/life-threatening 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.

Predictors of late cardiovascular complications in survivors of hematopoietic cell transplantation.

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.

Physiologic Frailty in Nonelderly Hematopoietic Cell Transplantation Patients: Results From the Bone Marrow Transplant Survivor Study

Importance Frailty results in decreased physiological reserve and diminished resistance to stressors; approximately 10% of those in the elderly population (those ≥65 years) are frail. High-intensity treatments and complications after hematopoietic cell transplantation (HCT) injure normal tissues and may increase the risk of frailty even among nongeriatric HCT patients. Objective To determine the prevalence of frailty in young adult HCT patients (18- to 64-year-olds) and siblings; and the impact of frailty on subsequent mortality in HCT survivors. Design, Setting, and Participants This cohort study, conducted in August 2015 examined 998 HCT survivors, who underwent transplant procedures between 1974 and 1998, who have survived at least 2 years after HCT, and 297 frequency-matched siblings. The study was performed at City of Hope or University of Minnesota with participants completing surveys at home or in the clinic. Hematopoietic cell transplantation survivors and siblings participating in the Bone Marrow Transplant Survivor Study (BMTSS) completed a frailty survey between February 13, 1999 and June 15, 2005 (median time since HCT: 7.9 years); HCT survivors were followed for subsequent mortality (median: 10.3 years from survey). Main Outcomes and Measures Prevalence and predictors of frailty; impact of frailty on subsequent mortality in HCT survivors. Frailty phenotype defined as exhibiting 3 or more of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The national Death Index, Social Security Death Index and medical records were used for mortality assessment as of December 21, 2011. Results The 998 HCT survivors were a mean (SD) of 42.5 (11.6) years of age, and the 297 matched siblings were 43.8 (10.9) years of age. The prevalence of frailty among young adult HCT patients exceeded 8%. The HCT survivors were 8.4 times more likely to be frail than their siblings (95% CI, 2.0-34.5; P = .003). Among HCT recipients, allogeneic HCT recipients with chronic graft-vs-host disease (GvHD) were at increased risk of frailty compared with autologous HCT (OR,15.02; 95% CI, 6.6-34.3; P < .001); resolved chronic GvHD (OR, 2.7; 95% CI, 1.1-6.9; P = .04). Cumulative incidence of subsequent all-cause mortality was 39.3% and 14.7% at 10 years for HCT recipients with and without frailty, respectively (P < .001). Frailty was associated with a 2.76-fold (95% CI, 1.7-4.4; P < .001) increased risk of subsequent mortality after adjusting for relevant prognosticators. Conclusions and Relevance The prevalence of frailty among young-adult HCT survivors approaches that seen in the elderly general population. Frail HCT survivors are at increased risk of subsequent mortality when compared with nonfrail survivors. This study identifies vulnerable populations needing close monitoring to anticipate and manage morbidity and prevent mortality.

Ethnic Differences in Chronic Health Conditions after Hematopoietic Cell Transplantation: A Report from the Bone Marrow Transplant Survivor Study

Hispanics have a greater risk of early treatment failure after hematopoietic stem cell transplantation (HCT) compared with non‐Hispanic whites. However, long‐term morbidity among Hispanics has not been described.

Long-term health-related outcomes in survivors of childhood cancer treated with hematopoietic cell transplantation (HCT) versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS)

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. Self-reported 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/life-threatening 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.

Knowledge Extraction of Long-Term Complications from Clinical Narratives of Blood Cancer Patients with HCT Treatments

Interactive information extraction (IE) systems supported by biomedical ontologies are intelligent natural language processing (NLP) tools to understand literature and clinical narratives and discover meaningful domain knowledge from unstructured text. This study developed integrated IE systems to detect treatment complications of blood cancer patients from Electrical Medical Records (EMR) in the Long-Term Follow-Up (LTFU) protocol following Hematopoietic Cell Transplantation (HCT). The performance of the proposed approach was very encouraging compared to the gold-standard datasets manually reviewed by domain experts. In addition, the NLP system identified significant amount of cases not caught by experts.

Prediction of cardiovascular disease among hematopoietic cell transplantation survivors

Cardiovascular disease (CVD) is a leading cause of late morbidity and mortality in hematopoietic cell transplantation (HCT) survivors. HCT-specific CVD risk prediction models are needed to facilitate early screening and prevention. In the current study, patients who underwent HCT at City of Hope (COH) and survived 1-year free of clinically evident CVD (N = 1828) were observed for the development of heart failure (HF) or coronary artery disease (CAD) by 10-years from index date (1 year from HCT). CVD occurred in 135 individuals (92 HF, 43 CAD). Risk prediction models were developed for overall CVD (HF and/or CAD) using COH-derived integer risk scores. Risk scores based on selected variables (age, anthracycline dose, chest radiation, hypertension, diabetes, smoking) achieved an area under the curve (AUC) and concordance (C) statistic of 0.74 and 0.72 for CVD; these varied from 0.70 to 0.82 according to CVD subtype (HF or CAD). A Fred Hutchinson Cancer Research Center case cohort (N = 580) was used to validate the COH models. Validation cohort AUCs ranged from 0.66 to 0.75. Risk scores were collapsed to form statistically distinct low-, intermediate-, and high-risk groups, corresponding to 10-year cumulative incidences of CVD of 3.7%, 9.9%, and 26.2%, respectively. Individuals in the high- and intermediate-risk groups were at 7.8-fold (95% confidence interval, 5.0-12.2) and 2.9-fold (95% confidence interval, 1.9-4.6) risk of developing CVD (referent group: low risk). These validated models provide a framework on which to modify current screening recommendations and for the development of targeted interventions to reduce the risk of CVD after HCT.

Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy

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. Self-reported 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/life-threatening 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.