Survivors Of Marrow Transplantation Research Articles

Body composition and late-occurring chronic health conditions after autologous stem cell transplantation for lymphoma.

Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late-onset CHCs and nonrelapse mortality after aPBSCT. Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre-aPBSCT body composition and new-onset grade 3-5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011-2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex-specific z-scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non-Hispanic Whites and 81% with non-Hodgkin lymphoma. The 5-year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%-56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI,0.50-0.96). The 10-year cumulative incidence of NRM was 16% (95% CI, 10-22). No body composition measure was associated with NRM. The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT.

Assessment of Risk Factors for Developing Iron Overload in Patients with Pediatric Cancer and Bone Marrow Transplant Survivors: A Single Center Retrospective Chart Review

Background: Pediatric cancer survivors and those with chronic hematologic disorders are at risk for iron overload secondary to frequent transfusion therapy. As this patient population increases in number due to improvement of therapies, it is essential to identify risk factors associated with the development of iron overload. Classifying these risk factors will help improve screening methods and assist in decreasing side effects from iron overload, such as iron deposition resulting in organ damage. Objective: Assessment of risk factors associated with the development of iron overload in pediatric cancer survivors and those who underwent bone marrow transplant. Methods: Retrospective chart review of patients who completed therapy for pediatric malignancy or underwent bone marrow transplant and were screened for iron overload utilizing magnetic resonance imaging (MRI). Iron overload was defined as T2* liver MRI with iron levels of >5mg/g dry weight. Individuals determined to screen positive for iron overload were evaluated for additional demographic and treatment variables, such as race, age at diagnosis, and total transfused blood volume, to assess for risk factors associated with the development of iron overload. Statistical analyses were performed via univariate and multivariate regression models of the variables collected. Results: We report a large cohort of patients with a mean age of 10.6 years who underwent screening T2* liver MRIs. Of 71 patients who underwent liver MRI screening, 89% met criteria for moderately severe iron overload. Blood volume administered (ml) and Non-White Race were found to be statistically significant in association with higher iron content. Mean iron content was 12.9 mg/g in the Non-White group versus 8.8 mg/g in the White group (p=0.0185). For every 100ml/kg increase in the cumulative blood volume transfused, the predicted iron content increased approximately 1 mg/g (p=0.0227); mean transfused blood volume was 340ml/kg among those who met criteria for iron overload versus 224ml/kg among those who did not (p=0.1858). We did not find any correlation between iron content and age at diagnosis, primary diagnosis, BMI at diagnosis, or gender. Conclusions: Iron overload continues to be a risk for pediatric cancer survivors and those who receive chronic transfusions. Our study revealed a statistically significant correlation between increased amount of blood transfusions and development of iron overload; however, no specific quantity of cumulative transfused blood volume was determined to be the threshold for risk. Our study also revealed a statistically significant correlation between Non-White race and the development of iron overload independent of cumulative transfused blood volume. It is possible there are race-based differences in iron metabolism that result in this increased risk. Further studies regarding specific quantities of blood transfusions, assessing physiologic characteristics of the Non-White patient population, and development of iron overload are needed. These findings indicate the importance of continuing to research the development of iron overload in the pediatric cancer and bone marrow transplant population, as well as provide guidance for understanding the risk each unique patient has for developing this complication.

Health care utilization by long-term survivors of blood or marrow transplantation-A Bone Marrow Transplant Survivor Study report.

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. 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 ≥2years 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. 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. 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.

Gene-Level Analysis of Anthracycline-Induced Cardiomyopathy in Cancer Survivors: A Report From COG-ALTE03N1, BMTSS, and CCSS

BackgroundAnthracyclines are highly effective in treating cancer, albeit with increased cardiomyopathy risk. Although risk is attributed to associations with single nucleotide polymorphisms (SNPs), multiple SNPs on a gene and their interactions remain unexamined. ObjectivesThis study examined gene-level associations with cardiomyopathy among cancer survivors using whole-exome sequencing data. MethodsFor discovery, 278 childhood cancer survivors (129 cases; 149 matched control subjects) from the COG (Children’s Oncology Group) study ALTE03N1 were included. Logic regression (machine learning) was used to identify gene-level SNP combinations for 7,212 genes and ordinal logistic regression to estimate gene-level associations with cardiomyopathy. Models were adjusted for primary cancer, age at cancer diagnosis, sex, race/ethnicity, cumulative anthracycline dose, chest radiation, cardiovascular risk factors, and 3 principal components. Statistical significance threshold of 6.93 × 10−6 accounted for multiple testing. Three independent cancer survivor populations (COG study, BMTSS [Blood or Marrow Transplant Survivor Study] and CCSS [Childhood Cancer Survivor Study]) were used to replicate gene-level associations and examine SNP-level associations from discovery genes using ordinal logistic, conditional logistic, and Cox regression models, respectively. ResultsMedian age at cancer diagnosis for discovery cases and control subjects was 6 years and 8 years, respectively. Gene-level association for P2RX7 (OR: 0.10; 95% CI: 0.04-0.27; P = 2.19 × 10−6) was successfully replicated (HR: 0.65; 95% CI: 0.47-0.90; P = 0.009) in the CCSS cohort. Additional signals were identified on TNIK, LRRK2, MEFV, NOBOX, and FBN3. Individual SNPs across all discovery genes, except FBN3, were replicated. ConclusionsIn our study, SNP sets having 1 or no copies of P2RX7 variant alleles were associated with reduced risk of cardiomyopathy, presenting a potential therapeutic target to mitigate cardiac outcomes in cancer survivors.

Risk of COVID-19 infection in long-term survivors of blood or marrow transplantation: a BMTSS report.

There is limited information regarding COVID-19 in long-term blood or marrow transplant (BMT) survivors. We leveraged the BMT Survivor Study (BMTSS) to address this gap. BMTSS included patients who underwent BMT at 1 of 3 sites in the United States between 1974 and 2014 and survived ≥2 years after BMT. A sibling cohort serves as a non-BMT comparison group. Participants (2430 BMT survivors; 780 non-BMT participants) completed the BMTSS survey between October 2020 and November 2021 about COVID-19 testing, risk mitigation behaviors, morbidity, and health care use. Median age at BMT was 46 years (range, 0-78 years) and median follow-up since BMT was 14 years (6-46 years); 76% were non-Hispanic White, 54% had received allogeneic BMT. The risk of COVID-19 infection was comparable for BMT survivors vs non-BMT participants (15-month cumulative incidence, 6.5% vs 8.1%; adjusted odd ratio [aOR]= 0.93; 95% confidence interval [CI], 0.65-1.33; P= .68). Among survivors, being unemployed (aOR 1.90; 95%CI, 1.12-3.23; P= .02; reference: retired) increased the odds of infection; always wearing a mask in public was protective (aOR= 0.49; 95%CI, 0.31-0.77; P= .002; reference: not always masking). When compared with COVID-positive non-BMT participants, COVID-positive BMT survivors had higher odds of hospitalization (aOR= 2.23; 95%CI, 0.99-5.05; P= .05); however, the odds of emergency department visits were comparable (aOR= 1.60; 95%CI= 0.71-3.58; P= .25). COVID-19 infection status did not increase the odds of hospitalization among BMT survivors (aOR=1.32; 95%CI= 0.89-1.95; P= .17) but did increase the odds of emergency department visits (aOR= 2.63; 95%CI, 1.74-3.98; P <.0001). These findings inform health care providers about the management of care for long-term BMT survivors during the ongoing pandemic.

Frailty and pre-frailty associated with physical functional performance and quality of life in breast cancer and bone marrow transplant survivors.

12064 Background: Frailty in cancer survivors poses a great challenge to health care providers. Frailty is associated with premature mortality, functional decline, and poor quality of life (QOL). We aimed to examine the associations of frailty and pre-frailty with physical functional performance and QOL in breast cancer survivors and bone marrow transplant (BMT) survivors. Methods: 43 breast cancer survivors and 55 BMT survivors who had received chemotherapy and did not have active cancer were recruited to the study. Based on Fried frailty phenotype, survivors were classified as frail if 3 or more criteria were present: unintentional weight loss, exhaustion, slow walking speed, low physical activity, and weakness. Pre-frail was classified if 1 or 2 criteria were present. Physical functional performance was assessed by Karnofsky performance scale (KPS) and continuous summary performance score (CSPS, comprises walking speed, standing balance, and repeated chair stands tests). p16INK4a, a marker for cellular senescence, was measured from survivors’ blood samples. QOL was measured using the 36-Item Short Form Survey. Groups were compared using chi-square test for categorical variables and rank-sum test for continuous variables. Results: Median age of survivors was 59 yrs (39% male). 13% of survivors (N = 13) were frail and 26% (N = 25) were pre-frail. Frail/pre-frail survivors tended to be older, male, and BMT survivors and had worse results for KPS, walking speed, repeated chair stands, and CSPS (p-values&lt;0.03). Frail/pre-frail versus non-frail survivors had a higher p16INK4a expression (p-value&lt;0.01). For QOL, frail/pre-frail survivors had lower median scores of physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, social functioning, bodily pain, and general health (p-values&lt;0.04), but the median scores of emotional well-being for frail/pre-frail and non-frail survivors were similar (p-value=0.06). Conclusions: Frailty and pre-frailty in a study of breast cancer and BMT survivors were associated with worse physical functional performance, higher p16INK4a expression, and lower quality of life. [Table: see text]

Cardiac iron overload in pediatric oncology and bone marrow transplant survivors.

e22022 Background: Cardiovascular late effects are a leading cause of mortality and morbidity in childhood cancer and Bone Marrow Transplant (BMT) survivors. In patients receiving chronic red blood cell transfusions, excess iron may be deposited in the liver, heart, and pituitary gland. Iron overload cardiomyopathy is characterized as a restrictive physiology with early diastolic dysfunction ultimately progressing to end-stage dilated cardiomyopathy. Iron loading in the heart can also lead to arrhythmias and increase myocardial ischemia reperfusion injury due to increased formation of reactive oxygen species. It is not yet known whether high transfused packed red blood cell (PRBC) volumes in cancer and BMT patients leads to cardiac iron deposition, and whether iron-induced cardiac injury contributes to the known cardiovascular late effects in these patients. Methods: 83 childhood cancer and BMT survivors with elevated serum ferritin levels and subsequent liver Magnetic Resonance (MR) imaging were identified. 18 patients (21.7%) who had liver iron content of &gt; 12mg/g (mean 16.0 ± 7.36 mg/g) also underwent Cardiac MRI (CMR) to determine cardiac iron content. Results: Median transfused blood volume was 393 ml/kg [95% Confidence Interval (CI) 170-780 ml/kg]. All 18 patients had at least one echocardiogram showing normal ventricular ejection fractions [mean 65.1 ± Standard Deviation (SD) 3.53%] and normal shortening fractions (mean 35.4 ± 3.67%). All patients had myocardial iron content within normal ranges (T2* relaxation time mean 35.1 msec ± 7.1 [normal &gt;20 msec], mean ± SD iron content 0.63± 0.2 mg/g dry weight, range 0.5-1.1). There was no association of cardiac iron content with transfused blood volume, anthracycline dose (mg/m2) or liver iron content (Pearson Correlation Coefficients 0.27, 0.29 and 0.89 respectively). Conclusions: Childhood cancer and BMT patients receive multiple PRBC transfusions to treat symptomatic anemia. It is currently unknown whether excess iron deposition in the heart contributes to the cardiac effects of impaired diastolic function and ultimately systolic dysfunction. In this study, 11 of 18 patients (61.1%) with high levels of liver iron had at least 1 other risk factor for the development of future cardiac dysfunction (either anthracycline exposure, radiation to the chest or total body irradiation or both). Larger studies are needed to determine whether oncology patients with high levels of iron deposition in their liver are also at risk for clinically significant cardiac iron loading, and what risk factors may exist for elevated myocardial iron content.

Adherence and satisfaction with remote cognitive training in blood or marrow transplant (BMT) survivors: The cognitive training and attitudes towards genetics (cTAG) study.

7009 Background: Cognitive impairment is prevalent in hematologic cancer survivors treated with BMT. There is a need for remote, accessible, and engaging interventions in order to mitigate adverse cognitive outcomes following treatment. We report on feasibility, satisfaction and preliminary efficacy of a remote cognitive training intervention in BMT survivors. Methods: Participants enrolled in the cTAG study were randomized to either using the online brain games Lumosity program daily for 12 weeks, or the waitlist arm. Cognitive function was assessed using a comprehensive battery covering executive function, processing speed, attention, memory and learning domains, and PROMIS Short Form4a for cognitive complaints. Participants’ satisfaction was measured using an exit survey. Standardized T-scores (mean: 50; standard deviation: 10), were used for domain-specific outcomes. An intention-to-treat analysis was used to model the change in cognition at 12 weeks compared to baseline, between study arms, controlling for baseline cognitive reserve, age, sex and race/ethnicity to enhance estimate precision. Results: Feasibility: 150 eligible patients were approached, 88 (58.7%) consented and 71 (80.7%) were randomized. Fifty-five patients completed the study (28 on active and 27 on waitlist arm). Post-randomization attrition rate was 19.7%. Median age at time of test was 58y (range: 27-74); 60% males, 83.6% Non-Hispanic White and 16.4% non-Hispanic Black, and 49% with low cognitive reserve. There were no significant differences between study arms. Adherence on active arm: Median of 87.5% for 4.9 days/week and 10/12 weeks. Preliminary Efficacy: Compared to the waitlist arm, scores improved for the active arm in attention (2.14 points, SE=1.01, p-value=0.039) and memory domains (5.63, SE=2.40, p-value=0.02). There was no significant change on cognitive complaints between the two arms. Satisfaction: Overall 78.2% of patients had no prior experience with cognitive training, 58.7% felt it helped their recovery, 82.6% found time commitment reasonable, 87% found it easy to follow, fun, engaging and appropriately challenging. The intervention had a 91.3% satisfaction rate; 73.9% indicating they would continue training and 87% would recommend it to others. Participants’ perceived benefit from training was highest for attention (89.1%), memory (73.9%), and visual tasks (69.6%). Only 11% of participants perceived benefits for real word tasks. Conclusions: The intervention was feasible, favorably rated, and associated with both perceived and objective improvements in attention and memory domains. Remote cognitive training carries several advantages for BMT patients including early and convenient at home administration supporting its clinical utility and potential long-term adoption following treatment. Clinical trial information: NCT03094026 .

Misdiagnosis of 46, XY DSD in a childhood Bone Marrow Transplantation survivor

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Financial Burden in Blood or Marrow Transplantation Survivors During the COVID-19 Pandemic: A BMTSS Report.

The financial burden experienced by blood or marrow transplant (BMT) survivors during the COVID-19 pandemic remains unstudied. We evaluated the risk for high out-of-pocket medical costs and associated financial burden experienced by BMT survivors and a sibling comparison group during the COVID-19 pandemic. This study included 2,370 BMT survivors and 750 siblings who completed the BMT Survivor Study survey during the pandemic. Participants reported employment status, out-of-pocket medical costs, and financial burden. Medical expenses ≥ 10% of the annual household income constituted high out-of-pocket medical costs. Logistic regression identified factors associated with high out-of-pocket medical costs and financial burden. BMT survivors were more likely to incur high out-of-pocket medical costs (11.3% v 3.1%; adjusted odds ratio [aOR], 2.88; 95% CI, 1.84 to 4.50) than the siblings. Survivor characteristics associated with high out-of-pocket medical costs included younger age at study (aORper_year_younger_age, 1.02; 95% CI, 1.00 to 1.03), lower prepandemic annual household income and/or education (< $50,000 US dollars and/or < college graduate: aOR, 1.96; 95% CI, 1.42 to 2.69; reference: ≥ $50,000 in US dollars and ≥ college graduate), > 1 chronic health condition (aOR, 2.82; 95% CI, 2.00 to 3.98), ≥ 1 hospitalization during the pandemic (aOR, 2.11; 95% CI, 1.53 to 2.89), and being unemployed during the pandemic (aOR, 1.52; 95% CI, 1.06 to 2.17). Among BMT survivors, high out-of-pocket medical costs were significantly associated with problems in paying medical bills (aOR, 10.57; 95% CI, 7.39 to 15.11), deferring medical care (aOR, 4.93; 95% CI, 3.71 to 6.55), taking a smaller dose of medication than prescribed (aOR, 4.99; 95% CI, 3.23 to 7.70), and considering filing for bankruptcy (aOR, 3.80; 95% CI, 2.14 to 6.73). BMT survivors report high out-of-pocket medical costs, which jeopardizes their health care and may affect health outcomes. Policies aimed at reducing financial burden in BMT survivors, such as expanding access to patient assistance programs, may mitigate the negative health consequences.

Potentially inappropriate medications in geriatric blood or marrow transplantation (BMT) survivors: A BMT Survivor Study report.

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. 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 ≥2years. 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. 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). 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.

Neighborhood disadvantage, health status, and health care utilization after blood or marrow transplant: BMTSS report

AbstractLiving in a disadvantaged neighborhood is associated with poor health outcomes. Blood or Marrow Transplant (BMT) survivors remain at risk of chronic health conditions requiring anticipatory management. We hypothesized that among BMT survivors, neighborhood disadvantage was associated with poor self-reported routine health care utilization and health. We leveraged data from BMTSS – a retrospective cohort study examining long-term outcomes among individuals surviving ≥2 y following BMT at three institutions between 1974 and 2014. Participants in this analysis completed the BMTSS survey (sociodemographics; chronic health conditions; time since routine check-up; self-reported health). The Area Deprivation Index (ADI) represented neighborhood disadvantage; this composite indicator of 17 census measures is a percentile rank (0 = least deprived to 100 = most deprived). Multivariable ordered logit regression adjusted for clinical factors and individual-level sociodemographics, modeling associations between ADI, time since routine check-up, and self-reported health. Among 2,857 survivors, median ADI was 24 (interquartile range: 10-46). Adjusting for self-reported individual-level socioeconomic indicators and chronic health conditions, patients in more disadvantaged neighborhoods had higher odds of reporting longer intervals since routine check-up (ORADI_continuous = 1.007, P < .001) and poorer health status (controlling for time since check-up; ORADI_continuous = 1.005, P = .003). Compared with patients living in the least disadvantaged neighborhood (ADI = 1), patients in the most disadvantaged neighborhood (ADI = 100), had twice the odds (ORADI = 1.007^99 = 2.06) of reporting no routine visits and 1.65-times the odds of reporting poor health (ORADI = 1.005^99 = 1.65). In BMT survivors, access to health care and health status are associated with area disadvantage. These findings may inform strategies to address long-term care coordination and retention for vulnerable survivors.

Pathological features of inflammatory myopathy as a manifestation of chronic graft‐versus‐host disease after allogeneic bone marrow transplantation

Chronic graft-versus-host disease (cGVHD) is the most important complication resulting in the death of bone marrow transplantation (BMT) survivors. It is also a relatively rare cause of inflammatory myopathy (IM). We report the case of a 46-year-old woman who developed severe cGVHD-related IM after BMT for myelodysplastic syndrome. She presented with severe muscle pain and weakness with cGVHD-related symptoms in other organs. Myopathological analysis showed moderate cell infiltration with remarkable necrotic and regenerative fibers. Sarcoplasm and capillaries expressed C5b9 and myxovirus resistance protein 1. Non-necrotic fibers in perifascicular regions expressed MHC-II. Steroid therapy did not sufficiently control cGVHD-related IM, and the patient was concurrently treated with an immunosuppressant. Our findings show that IM is a key manifestation of cGVHD and that the expression of interferon-inducible proteins in muscle pathology is useful for identifying cGVHD-related IM.

Association between Neighborhood Disadvantage and Health Status/Healthcare Utilization in Survivors of Blood or Marrow Transplantation (BMT) - a BMTSS Report

Background: Living in a disadvantaged neighborhood (reflecting neighborhood-level social determinants of health) is associated with poor health outcomes. BMT survivors remain at a high risk of long-term and late-occurring chronic health conditions that require anticipatory management. We hypothesized that neighborhood disadvantage would be associated with poor health status as reported by the BMT survivors, as well as poor utilization of the healthcare system.Methods: We leveraged data from BMTSS - a retrospective cohort study examining long-term outcomes among individuals who survived ≥2y following BMT performed at three institutions between 1974 and 2014. Participants in this analysis underwent a single BMT and completed the BMTSS survey, which captures sociodemographic characteristics and chronic health conditions. We graded chronic health conditions using CTCAE v5.0, and calculated a summative index that takes into account the number and grades of the conditions, where a higher score indicates more/worse conditions. The survey also captured self-reported health status (“In general would you say your health is: excellent, very good, good, fair or poor?”) and healthcare utilization (“When was your most recent routine check-up? <1y ago, 1-2y ago, 2-5y ago, ≥5y ago, never”). Neighborhood disadvantage was measured using the Area Deprivation Index (ADI), a validated composite indicator based on 17 US Census measures and percentiled as 0 (least deprived) to 100 (most deprived). BMT survivors were linked to ADI via census block group using home address at survey completion. Using multivariable ordered logit regression, we modeled the association between ADI and the odds of worse self-reported health or a longer time since a routine healthcare visit. Models were adjusted for available clinical factors (primary cancer diagnosis, donor source, conditioning intensity, chronic health conditions, chronic graft vs. host disease (GvHD), time from BMT) and individual-level sociodemographic characteristics (age at survey, sex, payor, race/ethnicity, education, income, marital status).Results: The cohort included 2,893 BMT survivors; median age at BMT was 47y (IQR: 30-58); median follow-up time was 9y (IQR: 5-16). Table 1 summarizes patient characteristics. Median ADI ranged from 14.0 in patients rating their health as excellent to 28.5 in those rating their health as poor, and from 21.0 in patients with visits <1y ago to 34.0 in patients reporting no visits [Fig 1]. In multivariable analyses, the odds of reporting worse health were higher for patients residing in more disadvantaged neighborhoods (OR per_unit_higher_ADI=1.005, p=0.003). Thus, for our cohort, a patient living in the most disadvantaged neighborhood (ADI=100) had 1.65 times the odds of reporting poor health compared to a patient living in the least disadvantaged neighborhood (ADI=1). Further, the odds of a longer time since the last routine physician visit were higher for patients living in more disadvantaged neighborhoods (OR per_unit_higher_ADI=1.007, p<0.001). Thus, a patient living in the most disadvantaged neighborhood had twice the odds (OR=2.06) of reporting no visits compared to a patient living in the least disadvantaged neighborhood.Conclusions: Conditional on surviving 2 or more years after BMT, living in a disadvantaged neighborhood was associated with poorer self-reported health and a longer time interval since a routine healthcare visit, after adjusting for self-reported individual socioeconomic indicators and chronic health conditions. The significant association between area deprivation and poorer self-reported health persisted after controlling for prior health care utilization. Our findings suggest that health status and access to healthcare are associated with characteristics of the built and social environment and deserve detailed examination in order to inform multi-level interventions that include policy. [Display omitted] DisclosuresArora: Syndax: Research Funding; Kadmom: Research Funding; Pharmacyclics: Research Funding.

Late-occurring venous thromboembolism in allogeneic blood or marrow transplant survivors: a BMTSS-HiGHS2 risk model

AbstractAllogeneic blood or marrow transplant (BMT) recipients are at risk for venous thromboembolism (VTE) because of high-intensity therapeutic exposures, comorbidities, and a proinflammatory state due to chronic graft-versus-host disease (GVHD). The long-term risk of VTE in allogeneic BMT survivors remains unstudied. Participants were drawn from the Blood or Marrow Transplant Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived ≥2 years after BMT. We analyzed the risk of VTE in 1554 2-year survivors of allogeneic BMT compared with 907 siblings. Using backward variable selection guided by minimizing Akaike information criterion, we created a prediction model for risk of late-occurring VTE. Allogeneic BMT survivors had a 7.3-fold higher risk of VTE compared with siblings (95% CI, 4.69-11.46; P < .0001). After a median follow-up of 11 years, conditional on surviving the first 2 years after BMT, the cumulative incidence of late-occurring VTE was 2.4% at 5 years, 4.9% at 10 years, and 7.1% at 20 years after BMT. The final model for VTE risk at 2 years post-BMT included History of stroke, chronic GVHD, Hypertension, Sex (male vs female) and Stem cell source (peripheral blood stem cells vs other) (“HiGHS2”) (corrected C-statistics: 0.73; 95% CI = 0.67-0.79). This model was able to classify patients at high and low VTE risk (10-year cumulative incidence, 9.3% vs 2.4% respectively; P < .0001). The BMTSS HiGHS2 risk model when applied at 2 years post-BMT can be used to inform targeted prevention strategies for patients at high risk for late-occurring VTE.

High-Intensity Healthcare Utilization and Costs Among Older 10+y Survivors of Allogeneic Blood or Marrow Transplantation (BMT): A Report from the BMT Survivor Study-2 (BMTSS-2)

Background: BMT survivors carry an inordinately high burden of long-term morbidity - a burden that increases as the survivor population ages as well as with time from BMT. This high burden places the survivors at high risk for hospitalizations and emergency room (ER) visits - referred to here as high-intensity healthcare utilization. However, the prevalence and predictors of high-intensity healthcare utilization by older (≥65y) BMT survivors who are 10+y from BMT and the costs remain unstudied. We used a multi-institutional study (BMTSS-2) to address this gap.Methods: We ascertained self-reported high-intensity healthcare utilization in the 2y prior to study participation from allogeneic BMT survivors who were ≥65y at study participation and had survived 10+y from BMT (n=82). Using Poisson regression with robust variance estimator, we compared utilization from the older cohort with a younger cohort (40-64y at study) of 10+y allogeneic BMT survivors (n=177), as well as an older cohort (65+y at study) of non-BMT siblings (n=217). Finally, we compared the average costs of ER visits and hospitalizations per patient among the three cohorts, using national age-adjusted estimates from CDC.Results: The median age of the older BMT cohort at study was 68y (65.0-89.3); the median length of follow-up was 16.4y (11.0-36.5) from BMT. The median age of the younger BMT cohort was 56.3y (40.2-64.9), with a median follow-up of 17.7y (5.4-40.5) from BMT. The median age of the sibling comparison group was 69.3y (65.0-90.5). The 3 cohorts were comparable with respect to gender, race/ethnicity, education and income. The prevalence of high-intensity healthcare utilization was greatest in the older BMT cohort at 65%, followed by the younger BMT cohort at 44% and lowest among the siblings at 34%. Older BMT Survivors vs. Siblings : After adjusting for age, gender, race, education, income, health status, health concerns and insurance, older survivors were 1.47 times more likely to report a high-intensity visit (95%CI, 1.09-1.20, p=0.011) when compared with siblings. Older vs. Younger BMT Survivors : After adjusting for sociodemographic factors, as well as primary cancer diagnosis, years since BMT, chronic graft vs. host disease (GvHD), health status, health concerns, and number of chronic health conditions, older BMT survivors were 1.32 times more likely to report a high-intensity visit (95%CI, 0.99-1.75, p=0.06) when compared with the younger BMT cohort. Older BMT Survivors : Among older BMT survivors, significant risk factors included lower household income and impaired health status. Compared to survivors with income greater than $75,000, those with income less than $20,000 were marginally more likely to report high-intensity visits (PR=1.51, 95%CI, 0.99-2.30, p=0.057). Compared to survivors reporting excellent or very good health status, the prevalence of high-intensity visit were 1.9 times greater for those with good health status (95%CI, 1.01-3.70, p=0.05) and 2.2 times greater for those reporting fair/poor health status (95%CI, 1.14-4.11, p=0.018). Estimated Costs : Assuming that the patients had one high-intensity visit in the 2y prior to study, a conservative estimate of the average cost of high-intensity visits per person was at least $13,810 for the older BMT survivors, $7,498 for the younger BMT survivors and $5,696 for the siblings.Conclusion: Sixty-five percent of older allogeneic BMT survivors who are 10+y from BMT report high-intensity healthcare utilization; they are more likely to utilize high-intensity health care than younger survivors and same-age sibling controls. This high-intensity healthcare translates into a highly conservative 2.4-fold higher healthcare costs for the older BMT survivors when compared with a similarly-aged non-BMT comparison group. A coordinated effort among healthcare providers is necessary to ensure efficient and cost-effective anticipatory care for long-term BMT survivors to prevent high-intensity healthcare utilization several years after BMT. DisclosuresArora:Takeda Oncology: Consultancy.

Reduction in Late Mortality after Autologous Blood or Marrow Transplantation (autoBMT) in Childhood - a Report from the Blood or Marrow Transplant Survivor Study-2 (BMTSS-2)

Background: AutoBMT is used with a curative intent for several types of childhood cancer. However, there is paucity of information regarding the long-term outcome after autoBMT performed in childhood, and whether mortality rates have changed over the past 4 decades. We address these gaps by examining all-cause, relapse-related [RRM] and non-relapse-related [NRM] mortality in patients undergoing autoBMT between 1980 and 2010 at City of Hope, University of Minnesota or University of Alabama at Birmingham. Methods: To be included in this analysis, patients had to have received a single autoBMT before age 22y, and survived ≥2y after transplantation. Vital status information was ascertained as of December 31, 2016, using medical records, the National Death Index (NDI), and Accurint databases. Information on the cause of death was obtained from the NDI Plus program and medical records. Using Kaplan-Meier techniques, we describe overall survival conditional on surviving 2y and 15y from autoBMT. We describe cumulative incidence of RRM and NRM using competing risk methods. We also describe trends in all-cause mortality over 3 time periods: <1990, 1990-1999 and 2000-2010. Standardized mortality ratio (SMR) was used to compare the mortality of this cohort to the age- sex-, and calendar-specific mortality of the US general population. Proportional subdistribution hazards model (Fine-Gray) for competing risks was used for identifying predictors of late mortality (demographics, primary disease, conditioning agents, and disease status at autoBMT). Results: In this cohort of 364 2+y survivors of autoBMT performed in childhood, the most common primary diagnoses were Hodgkin lymphoma (HL: 26%), neuroblastoma (23%), acute myeloid leukemia (AML: 13%), acute lymphoblastic leukemia (ALL: 12%), and non-Hodgkin lymphoma (NHL: 9%). The distribution of the cohort over the 3 time periods was: <1990 (20%); 1990-1999 (37%); 2000-2010 (43%). After a median follow-up of 14.2y, 104 deaths were observed in this 2+y survivor cohort. The leading causes of death included primary disease (49.5%), subsequent malignant neoplasms (21.0%) and infection (18.2%). The 10y cumulative incidence of RRM (13.6%) exceeded that of NRM (10.2%) (Fig 1). Overall, the cohort was at a 23-fold higher risk of late mortality (SMR 23.6, 95% CI 19.3-28.6), when compared with the general population. The SMR was significantly increased in all groups of primary diagnoses; ALL (SMR 27.0), AML (SMR 7.8), HL (SMR 15.1), NHL (SMR 13.5), and neuroblastoma (SMR 60.7). Conditional on surviving 2y, 5y, 10y and 15y, the overall survival was 81.9%, 91.4%, 95.6% and 99.4%, respectively. Mortality rates continued to remain higher than the general population among those who had survived at least 10y after autoBMT (SMR 12.4, 95% CI 4.9-25.1), but approached those of the general population among the 15+y survivors (SMR 3.0, 95%CI, 0.5-9.4). The all-cause 10y cumulative mortality rate declined over the 3 eras (<1990: 35.1%, 1990-1999: 24.4%; 2000-2010: 20.6%, p=0.02) (Fig 2). Adjusting for demographic and clinical variables, as well as preparative regimens, the hazard ratio (HR) of all-cause mortality declined in the more recent treatment eras (<1990 (referent group): HR=1.0; 1990-1999: HR=0.5, 95%CI, 0.3-0.9, p=0.02; 2000-2010: HR=0.4, 95%CI, 0.2-0.8, p=0.007). Conclusion: Taken together, these findings suggest that the mortality rates of autoBMT recipients are significantly higher than those of the general population. Relapse is the leading cause of death for the first 10y after autoBMT. Importantly, there has been a significant decline in all-cause mortality in children undergoing autoBMT over the past 4 decades. [Display omitted] DisclosuresArora:Takeda Oncology: Consultancy.

Reduction in Late Mortality Among Patients With Multiple Myeloma Treated With Autologous Peripheral Blood Stem Cell Transplantation—A Blood or Marrow Transplant Survivor Study Report

Therapeutic practices for multiple myeloma (MM) have evolved, such that novel-agent–based therapy and autologous peripheral blood stem cell transplantation (aPBSCT) is the current standard. Whether cause-specific mortality has changed with time remains unclear. We examined late cause-specific mortality among patients with MM receiving aPBSCT from 1989 to 2014. We conducted a prospective cohort study using participants enrolled in the enrolled in the Blood or Marrow Transplant Survivor Study. We created 3 eras to reflect changing MM therapy: <2000 (pre-thalidomide); 2000-2005 (thalidomide); 2006-2014 (lenalidomide). We used Kaplan-Meier techniques and Cox regression for examining all-cause mortality, and subdistribution hazards models for cause-specific mortality. In total, 1906 patients were followed up for a median of 9.2 years. Conditional on surviving 2 years, the 10-year overall survival was 45%. The 10-year cumulative incidence of myeloma- and non-myeloma-related mortality was 33% and 13%, respectively. Multivariable analysis showed declining MM-specific mortality (subdistribution hazard ratio [SHR]2000-2005 = 0.80, 95% confidence interval [CI], 0.60-1.07; SHR2006-2014 = 0.46, 95% CI, 0.34-0.62; referent group: <2000), infection-related mortality (SHR2000-2005 = 0.50, 95% CI, 0.29-0.85; SHR2006-2014 = 0.35, 95%CI 0.21-0.60; referent group: <2000) and cardiovascular disease-related mortality (SHR2000-2005 = 0.45, 95% CI 0.20-0.99; SHR2006-2014 = 0.41, 95% CI 0.18-0.93; referent group: <2000). Although primary disease remains the major cause of late mortality, we observed a significant temporal decline in myeloma-, infection-, and cardiac-related late mortality over the past 25 years.

Longitudinal trajectory of frailty in blood or marrow transplant survivors: Report from the Blood or Marrow Transplant Survivor Study.

Blood or bone marrow transplantation (BMT) survivors with frailty are at a higher risk of subsequent mortality. Longitudinal trends in the frailty state are not known and could help identify vulnerable subpopulations at risk of subsequent adverse events. This study included a cohort of 470 autologous and allogeneic BMT recipients who had survived ≥2 years after BMT and completed a baseline questionnaire (t1) at a median of 7.3 years after BMT and a follow-up questionnaire (t2) 13.2 years after t1. The main outcome was change in frailty state between t1 and t2. Frailty phenotype was defined as exhibiting ≥3 of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The following categories of change in frailty state were evaluated: worsened, improved, and stable. Of the 470 participants, 36.4% were aged ≥60 years at t1, and 50.6% were men. The prevalence of frailty increased from 4.8% at t1 to 9.6% at t2. Worsening was observed in 18.8% of patients, and improvement was reported in 9.7%. Pre-BMT exposure to vincristine (odds ratio [OR], 2.1; 95% CI, 1.3-3.39) was associated with worsening. Female sex (OR, 1.5; 95% CI, 0.93-2.4) was associated with a trend toward worsening. Pre-BMT exposure to vincristine (OR, 2.79; 95% CI, 1.44-5.43), a history of chronic graft-versus-host disease (OR, 2.58; 95% CI, 1.2-5.5), and grade 3 and 4 chronic health conditions at t1 (OR, 2.1; 95% CI, 1.08-4.33) were associated with frailty at t2. In a cohort of BMT survivors who were followed longitudinally for a median of 20.6 years from BMT, the frailty status worsened for approximately20% over a 13-year timespan. BMT survivors who are at risk for worsening frailty could benefit from targeted interventions.

Coronary Heart Disease Risk in Blood or Marrow Transplant Survivors

INTRODUCTION: Exposure to total body irradiation (TBI) increases the risk for cardiovascular risk factors (CVRFs) such as diabetes, hypertension and dyslipidemia in Blood or Marrow Transplant (BMT) survivors with the potential to increase the risk of post-BMT Coronary Heart Disease (CHD). Chest radiation is associated with accelerated atherosclerosis in conventionally treated patients. These factors, with or without additional factors such as smoking likely place BMT survivors at a high risk for CHD. Yet, a comprehensive evaluation of the risk of late-occurring CHD in BMT survivors is lacking. We addressed this gap using the resources offered by the BMT survivor study (BMTSS). METHODS: BMTSS includes patients transplanted between 1974 and 2014 at 3 US sites, and who had survived ≥2 years after BMT, and were alive and ≥18 years at BMTSS survey completion. The BMTSS survey asked participants to report chronic health conditions diagnosed by their healthcare provider (including CHD, diabetes, hypertension and dyslipidemia), along with age at diagnosis. The participants self-reported sociodemographics and health behaviors. Information regarding primary cancer diagnosis, therapeutic exposures, donor type, stem cell source, and history of chronic graft vs. host disease (GvHD; for allogeneic BMT recipients) was abstracted from medical records. A cohort of 1,131 siblings completed the BMTSS survey and served as a comparison group. We obtained informed consent from all participants. RESULTS: The study included 3,479 BMT survivors; 50.3% had received an allogeneic BMT, 54.8% were males, and 71.4% were non-Hispanic whites. Median age at study participation was 59 years (interquartile range [IQR]: 48-66 years) for BMT survivors and 57 years (IQR: 46-64 years) for siblings. BMT survivors were followed for a median of 9 years (range: 2-41 years) from BMT. CHD developed after BMT in 122 BMT survivors (52 allogeneic, 70 autologous). BMT recipients compared with siblings: After adjusting for sociodemographics and comorbidities, allogeneic BMT survivors were at a 7.2-fold higher odds (95%CI: 4.0-13.0, p&amp;lt;0.0001) and autologous BMT recipients at a 11.7-fold higher odds (95%CI: 6.8-20.2, p&amp;lt;0.0001) of reporting CHD as compared to siblings. Allogeneic BMT survivors: The 20 year cumulative incidence of CHD was 4.7% for allogeneic BMT recipients. Increasing age at BMT (HR=1.05/year, 95%CI: 1.02-1.07, p&amp;lt;0.0001), male sex (HR=2.09, 95%CI: 1.14-3.82, p=0.017), history of CVRFs (HR=3.6, 95%CI: 1.72-7.41, p=0.0006), and pre-BMT targeted chemotherapy such as tyrosine kinase inhibitors (HR=2.7, 95%CI: 1.10-6.77, p=0.030) were associated with increased CHD risk. The 20 year cumulative incidence of CHD among patients with CVRFs was 6.6% vs. 1.9% (p=0.005) among those who did not have CVRFs (Fig 1). Autologous BMT survivors: The 20 year cumulative incidence of CHD was 9.1% for autologous BMT recipients. The risk factors for CHD in autologous BMT survivors included: increasing age at BMT (HR=1.06/year, 95%CI: 1.03-1.09, p&amp;lt;0.0001), male sex (HR=2.3, 95%CI: 1.30-3.90, p=0.004), history of smoking (HR=1.66, 95%CI: 1.03-2.67, p=0.038), CVRFs (HR=1.77, 95%CI: 1.04-3.01, p=0.036), arrhythmia (HR=1.85, 95%CI: 1.01-3.42, p=0.048) and history of pre-BMT chest radiation (HR=4.56, 95%CI: 2.1-9.88, p=0.0001). For every 1 Gray increase in the dose of chest radiation, there was a 4% increase in the risk of CHD, p=0.0002. The 20 year cumulative incidence of CHD among patients with CVRFs was 10.2% vs. 7.4% among those who did not have CVRFs (p=0.04) (Fig 2). CONCLUSION: BMT survivors are at a 7-fold to 12-fold higher risk of CHD compared with a sibling comparison group. CVRFs are independent risk factors for CHD both among allogeneic and autologous BMT recipients. Pre-BMT chest radiation further increases this risk in autologous BMT recipients. These findings suggest a need for aggressive management of CVRFs in BMT recipients to prevent CHD-related morbidity. Disclosures Gangaraju: Sanofi Genzyme, Consultant for Cold Agglutinin Disease: Consultancy. Weisdorf:FATE Therapeutics: Consultancy; Incyte: Research Funding. Arora:Pharmacyclics: Research Funding; Kadmon: Research Funding; Syndax: Research Funding; Fate Therapeutics: Consultancy.