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Background: Patients undergoing autologous hematopoietic cell transplantation (HCT) have a >2‐fold risk of developing cardiovascular disease (CVD; heart failure, myocardial infarction, and stroke), compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in nononcology patients but is not as well studied in patients who underwent HCT and survivors of HCT.The objective of this study was to examine the association between CAC and CVD risk and outcomes after HCT in patients with lymphoma. Methods: This was a retrospective cohort study of 243 consecutive patients who underwent a first autologous HCT for lymphoma between 2009 and 2014. CAC (Agatston score) was determined from chest computed tomography obtained <60 days from HCT. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CIs), adjusted for covariates (age, conventional risk factors [e.g., hypertension and dyslipidemia], and cancer treatment). Results: The median age at HCT was 55.7 years (range, 18.5–75.1 years), 59% were male, and 60% were non‐Hispanic White. The prevalence of CAC was 37%. The 5‐year CVD incidence for the cohort was 12%, and there was an incremental increase in the incidence according to CAC score: 0 (6%), 1–100 (20%), and >100 (32%) (p =.001). CAC was significantly associated with CVD risk (HR, 3.0; 95% CI, 1.2–7.5) and worse 5‐year survival (77% vs. 50%; p <.001; HR, 2.0; 95% CI, 1.1–3.4), compared to those without CAC. Conclusions: CAC is independently associated with CVD and survival after HCT. This highlights the importance of integrating readily available imaging information in risk stratification and decision‐making in patients undergoing HCT, which sets the stage for strategies to optimize outcomes after HCT. Hematopoietic cell transplantation (HCT) survivors have an increased risk of cardiovascular disease (CVD) compared to the general population, and therefore thorough assessment of cardiovascular risk before HCT is essential. This study showed that the coronary artery calcium (CAC) score, obtained from routine pretransplant imaging, is significantly associated with CVD posttransplant and is a useful addition to traditional cardiovascular risk factors. Further prospective studies are needed to understand how CAC screening should be formally incorporated into pretransplant workup, cardiovascular risk assessment, and clinical decision‐making and its effect on posttransplant outcomes. [ABSTRACT FROM AUTHOR]

Background: Blood or marrow transplantation (BMT) survivors carry a high burden of morbidity, yet health care utilization by this vulnerable population remains understudied. Patterns and predictors of various domains of health care utilization in long‐term BMT survivors were evaluated. Methods: Study participants were drawn from the Bone Marrow Transplant Survivor Study (BMTSS). Patients transplanted between 1974 and 2014 at one of three transplant centers who had survived ≥2 years after BMT and were aged ≥18 years at the time of the study were included. A BMTSS survey served as the source of data for health care utilization, sociodemographics, and chronic health conditions. Domains of health care utilization in the 2 years preceding study participation included routine checkups, BMT‐related visits, transplant/cancer center visits, emergency room (ER) visits, hospitalizations, and high health care utilization (≥7 physician visits during the 2 years before the study). Clinical characteristics and therapeutic exposures were abstracted from medical records. Results: In this cohort of 3342 BMT survivors (52% allogeneic), the prevalence of health care utilization declined over time since BMT for both allogeneic and autologous BMT survivors, such that among those who had survived ≥20 years, only 49%–53% had undergone routine checkups, 37%–38% reported BMT‐related visits, and 28%–29% reported transplant/cancer center visits. The presence of severe/life‐threatening conditions and chronic graft‐vs‐host disease increased the odds of health care utilization across all domains. Lower education, lack of insurance, and Hispanic ethnicity were associated with a lower prevalence of routine checkups and/or transplant/cancer center visits. Lower income increased the odds of ER visits but reduced the odds of hospitalizations or high health care utilization. Conclusions: This study identified vulnerable populations of long‐term BMT survivors who would benefit from specialized risk‐based anticipatory care to reduce high health care utilization, ER visits, and hospitalizations. Health care utilization (including routine medical checkups) declines with increasing time since blood or marrow transplantation, except among survivors with severe/life‐threatening chronic health conditions as well as those with chronic graft‐vs‐host disease. Lower education and lack of insurance are associated with lower health care utilization. [ABSTRACT FROM AUTHOR]

Background: A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied. Methods: Seven hundred eighty‐nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255‐item survey self‐reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life‐threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3–5 conditions. Logistic regression was used to estimate the risk of grade 3–4 conditions in BMT recipients who were alive at the time of this study compared with siblings. Results: The median age at transplantation was 11.3 years (range, 0.4–22.0 years), and the median length of follow‐up was 11.7 years (range, 2.0–45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3–4 condition was 53.8% (95% CI, 46.7%–60.3%). The adjusted odds ratio of a grade 3–4 condition was 15.1 in survivors (95% CI, 9.5–24.0) compared with siblings. The risk of a grade 3–5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01–1.05) and was higher among females (HR, 1.27; 95% CI, 1.02–1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27–2.31), and those reporting chronic graft‐versus‐host disease (HR, 1.38; 95% CI, 1.09–1.74). Conclusions: Two‐year survivors of allogeneic BMT in childhood have an increased risk of grade 3–4 chronic health conditions compared with siblings, suggesting the need for long‐term follow‐up. Two‐year survivors of allogeneic bone marrow transplantation in childhood have a substantially increased risk of chronic health conditions compared with siblings. By age 35 years, more than one half of bone marrow transplantation recipients had a severe or life‐threatening chronic health condition. [ABSTRACT FROM AUTHOR]

Background: Blood or marrow transplantation (BMT) is increasingly offered to older individuals with hematologic malignancies. The high prevalence of chronic health conditions in such individuals necessitates use of multiple medications. Beers Criteria represent a list of potentially inappropriate medications (PIMs) shown to increase the risk of health problems in the elderly. We sought to determine the prevalence and predictors of PIM use in older BMT survivors and identify associations with health problems. Methods: Study participants were drawn from the BMT Survivor Study, a cohort study of patients transplanted at three US transplant centers between 1974 and 2014 and surviving ≥2 years. For this report, the survivors were aged ≥65 years. Siblings served as a comparison group. Participants self‐reported sociodemographics, chronic health conditions, and medication use. Logistic regression analyses identified predictors of PIM use and associations with health problems. Results: Overall, PIM use was comparable between BMT survivors (49.4%) and siblings (49.3%) (odds ratio [OR] = 0.9; 95% CI, 0.7–1.2); however, BMT survivors were more likely to use >1 PIM (17.4% vs. 12.4%; OR = 1.5; 95% CI, 1.01–2.4) and central nervous system–related PIMs (8.3% vs. 4.3%; OR = 2.18; 95% CI, 1.17–4.09). Predictors of PIM use included presence of severe/life‐threatening chronic health conditions (OR = 1.5; 95% CI, 1.1–2.0), and chronic graft versus host disease (OR = 1.7; 95% CI, 1.1–2.7). Survivors taking >1 PIM reported more issues with vertigo (OR = 2.3; 95% CI, 1.1–4.7), balance (OR = 2.6; 95% CI, 1.7–4.1), faintness/dizziness (OR = 2.8; 95% CI, 1.8–4.6), and personal care (OR = 4.5; 95% CI, 1.4–14.8). Conclusions: This study shows the health problems associated with PIM use and identifies vulnerable populations at higher risk for PIM use, providing evidence for caution in using PIMs in high‐risk populations. Older blood or marrow transplantation survivors were more likely to use multiple potentially inappropriate medications than a sibling comparison group. Survivors with multimorbidity and/or chronic graft versus host disease were more likely to use these medications; survivors taking multiple potentially inappropriate medications reported several health problems. [ABSTRACT FROM AUTHOR]

Background: Obesity at diagnosis of childhood acute lymphoblastic leukemia (ALL) is associated with greater risk of relapse; whether this association extends to obesity during maintenance is unstudied. Methods: This study used data from AALL03N1 to calculate median body mass index (BMI) for 676 children over 6 consecutive months during maintenance therapy; BMI percentile (BMI%ile) were operationalized as normal/underweight (<85%ile), overweight/obese (85%–98%ile), and extreme obesity (≥99%ile). Hazard of relapse was estimated using multivariable proportional subdistributional hazards regression after adjusting for all relevant demographic and clinical predictors. Results: Median age at study enrollment was 6 years and median length of follow‐up was 7.9 years. Overall, 43.3% of the cohort was underweight/normal weight, 44.8% was overweight/obese, and 11.8% had extreme obesity. Cumulative incidence of relapse at 4 years from study enrollment was higher among those with extreme obesity (13.6% ± 4.5%) compared to those with underweight/normal weight (9.0% ± 2.1%). Multivariable analysis revealed that children with extreme obesity had a 2.4‐fold (95% confidence interval [CI], 1.1–5.0; p =.01) greater hazard of relapse compared to those who were underweight/normal weight. Overweight/obese patients were at comparable risk to those who were underweight/normal weight (hazard ratio, 0.8; 95% CI, 0.4–1.6). Erythrocyte thioguanine nucleotide (TGN) levels were significantly lower among children with extreme obesity compared to those with underweight/normal weight (141.6 vs. 168.8 pmol/8 × 108 erythrocytes; p =.0002), however, the difference in TGN levels did not explain the greater hazard of relapse among those with extreme obesity. Conclusions: Extreme obesity during maintenance therapy is associated with greater hazard of relapse in children with ALL. Underlying mechanisms of this association needs further investigation. Lay summary: Findings from this study demonstrate that extreme obesity during maintenance therapy is associated with a greater hazard of relapse among children with acute lymphoblastic leukemia.We show that children with obesity have lower levels of erythrocyte thioguanine nucleotides even after adjusting for adherence to oral chemotherapy.However, these lower levels do not explain the greater hazard of relapse, paving the way for future studies to explore this association. Extreme obesity during maintenance therapy for childhood acute lymphoblastic leukemia is associated with twofold greater risk of relapse. Erythrocyte thioguanine nucleotide levels decline as body mass index increases; lower levels do not explain greater relapse risk. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic cell transplantation (HCT) recipients have increased risk of developing glucose intolerance and diabetes mellitus (DM). The strongest risk factor for glucose intolerance is being overweight/obese, as determined by body mass index (BMI), which does not account for differences in body composition. We examined the association between body composition measures from pre-HCT CT and early-onset (=30 days) de novo glucose intolerance after HCT, and determined its impact on nonrelapse mortality (NRM). Methods: This study included 749 patients without pre-HCT DM. Skeletal muscle loss [abnormal skeletal muscle gauge (SMG)] and abnormal visceral adiposity (VA) were defined by sex-specific tertiles. Fine-Gray proportional subdistribution HR estimates and 95% confidence intervals (CI) were obtained to determine the association between muscle loss and VA and development of glucose intolerance. 1 year NRM was calculated for patients alive at day 30. Results: Median age at HCT was 50.2 years. By day 30, 8.1% of patients developed glucose intolerance and 731 remained alive. In multivariable analysis, abnormal SMG was associated with increased risk of glucose intolerance in nonoverweight (BMI < 25 kg/m2) patients (HR = 3.00; 95% CI, 1.15-7.81; P = 0.024); abnormal VA was associated with increased risk of glucose intolerance in overweight/obese patients (HR = 2.26; 95% CI, 1.24-4.12; P = 0.008). Glucose intolerance was independently associated with NRM (HR = 1.88; 95% CI, 1.05-3.39; P = 0.035). Conclusions: Abnormal SMG and VA were associated with glucose intolerance in nonoverweight and overweight/obese patients, respectively, which contributed to increased risk of 1 year NRM. Impact: This information may guide personalized interventions to decrease the risk of adverse outcomes after HCT. [ABSTRACT FROM AUTHOR]

Background Risk of nonrelapse mortality (NRM) after hematopoietic cell transplantation (HCT) is high. Patient-level clinical prediction models such as the HCT–comorbidity index (HCT-CI) help identify those at increased risk for NRM, but the independent contribution of social determinants of health on HCT outcomes is not well characterized. Methods This study included 1602 patients who underwent allogeneic HCT between 2013 and 2019 at City of Hope. Census tract–level social vulnerability was measured using the social vulnerability index (SVI). Fine-Gray multivariable regression evaluated the association between SVI and 1-year NRM. Subgroup analysis examined risk of NRM across combined SVI and HCT-CI categories and by race and ethnicity. Results Cumulative incidence of 1-year NRM after HCT was 15.3% (95% confidence interval [CI] = 13.6% to 17.1%). In multivariable analysis, patients in the highest SVI tertile (highest social vulnerability) had a 1.4-fold risk (subdistribution hazard ratio [sHR] = 1.36, 95% CI = 1.04 to 1.78) of NRM compared with individuals in the lower tertiles; patients in the highest SVI tertile who also had elevated (≥3) HCT-CI scores had the highest risk (sHR = 1.81, 95% CI = 1.26 to 2.58) of 1-year NRM (reference: lower SVI tertiles and HCT-CI < 3). High social vulnerability was associated with risk of 1-year NRM in Asian (sHR = 2.03, 95% CI = 1.09 to 3.78) and Hispanic (sHR = 1.63, 95% CI = 1.04 to 2.55) but not non-Hispanic White patients. Conclusions High social vulnerability independently associated with 1-year NRM after HCT, specifically among minority populations and those with a high comorbidity burden at HCT. These findings may inform targeted approaches for needs assessment during and after HCT, allowing for timely interventions to improve health outcomes in at-risk patients. [ABSTRACT FROM AUTHOR]