Adult Hematopoietic Cell Transplantation Survivors Research Articles

Symptom burden in adult survivors of allogeneic hematopoietic stem cell transplantation.

6557 Background: Progress in allogeneic hematopoietic cell transplantation (HCT) and supportive care has significantly improved transplant outcomes and expanded the number of HCT survivors. A growing responsibility exists to address long-term morbidity and symptom burden. We sought to investigate symptom burden in adult survivors of HCT using a set of validated tools. Methods: We analyzed adults aged 19 years or older with hematologic malignancies who were treated with allogenic HCT at our institution from June 2018 to November 2022. Patients required at least one visit to our survivorship clinic for inclusion. We assessed symptom burden using the National Comprehensive Cancer Network (NCCN) Survivorship Assessment Questionnaire, which is a 25-question survey designed to assesses symptoms related to the following domains: cardiac, mood, cognition, fatigue, lymphedema, hormonal, pain, sexual dysfunction, and sleep. The short physical performance battery (SPPB) and short blessed test were used to assess physical function and conduct cognitive screen, respectively. Finally, we compared scores between patients <60 and ≥60 years old to examine an association between age and post-transplant symptoms. Results: A total of 152 patients have a median age of 61 years (range 21-76); 59.2% were males, and 28.5% had a BMI ≥30. Median Hematopoietic Cell Transplantation-specific Comorbidity Index was 3. The most common indication for transplant was acute myeloid leukemia (48.0%), and the most common donor type was matched unrelated (57.2%). The median time from transplant to the first survivorship clinic visit was 99 days. The most common symptom domains affected, according to the NCCN questionnaire results, were fatigue (50.7%), sleep (45.3%), and cognition (42.0%) whereas the least affected domains were pain (29.5%), cardiac (26.2%), and sexual (19.4%). When we stratified patients by <60 years old and ≥60 years old, we saw similar rates of reported symptoms, particularly regarding sleep disorder (44.3% vs. 45.7%, respectively), mood disturbance (31.4% vs. 34.1%, respectively), and sexual dysfunction (17.9% vs. 20.5%, respectively). Older patients, however, had higher rates of physical impairment according to SPPB scores (50.0% vs. 15.7%, OR = 5.4 [95% CI = 2.2-14.3]). Blessed test showed impaired cognitive screen in 7.2% without a significant difference based on age. Conclusions: Adult survivors of allogeneic HCT at 3-month post-transplant commonly suffer from symptoms across a variety of domains, especially pertaining to fatigue, sleep, and cognition. These symptoms affect both younger and older patients, although older patients are more likely to have physical impairment. The NCCN Survivorship Assessment Questionnaire captures a number of symptoms related to quality of life and can be more widely utilized as a tool to evaluate survivorship symptoms in patients who undergo HCT.

Impact of Hematopoietic Cell Transplantation on Cardiovascular Risk Factors and Insulin Sensitivity

The use of hematopoietic cell transplantation (HCT) for treating malignant conditions in children has increased over the past five decades, leading to a growing population of long-term survivors.This population of childhood HCT survivors faces increased risks of adverse medical effects due to cancer treatments, including adverse cardiovascular disease (CVD) risk factors such as metabolic syndrome, insulin resistance. but the impact of exposure to HCT preparative conditioning regimen has not been clearly delineated. These risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance (IR), are significant contributors to premature cardiovascular disease and represent a leading cause of non-relapse deaths in childhood cancer and HCT survivors. This study aimed to assess the early development of CVD risk factors and their relationship to insulin resistance in a large population of pediatric and young adult HCT survivors of childhood hematologic malignancies. The study compared their cardiovascular risk profiles, insulin resistance (measured by euglycemic hyperinsulinemic clamp studies), and body composition (determined by dual X-ray absorptiometry - DXA) with a cohort of sibling controls. We enrolled 151 HCT recipients (26.36 ±0.90 years at study enrollment; time since HCT of 2.6-31.5 years) and 92 sibling controls to complete at cardiovascular risk assessment including insulin sensitivity by hyperinsulinemic euglycemic clamp, anthropometry, body composition by dual X-ray absorptiometry, blood pressure, and serum biomarkers. We used linear models to test for mean differences in all continuous outcomes between survivors and siblings, accounting for intra-family correlations with generalized estimating equations. Recipients of HCT were found to have lower insulin sensitivity and more likely to have adverse CVD risk factors in comparison to their healthy siblings. Significantly higher percent fat mass and visceral adipose tissue, and significantly lower lean body mass were noted in HCT recipients than sibling controls despite having a similar body mass index between the two groups. Total body irradiation in the conditioning regimen was one of the strongest factors associated with lower insulin sensitivity, dyslipidemia and abnormal body composition leading to sarcopenic obesity. This study reveals that pediatric and young adult HCT survivors are more insulin resistant and have a higher prevalence of adverse cardiovascular risk factors compared to sibling controls. The presence of cardiovascular risk factors at a relatively young age raises concerns about an escalating trajectory of cardiovascular disease in this population. Therefore, regular monitoring of HCT survivors for cardiometabolic risk factors and early intervention will be crucial for preventing cardiovascular-related complications in the future. The findings underscore the importance of survivorship care for pediatric and young adult HCT survivors, with a focus on managing cardiovascular risk factors and promoting a healthy lifestyle to mitigate long-term adverse effects. Early identification and targeted interventions can significantly improve the long-term health outcomes of this vulnerable population, reducing the burden of cardiovascular disease and related complications.

Severity of Chronic Graft-versus-Host Disease and Late Effects Following Allogeneic Hematopoietic Cell Transplantation for Adults with Hematologic Malignancy

The study aimed to determine the association of chronic graft-versus-host disease (cGVHD) diagnosis and severity with the development of subsequent neoplasms (SN) and nonmalignant late effects (NM-LE) in 2-year disease-free adult survivors following hematopoietic cell transplantation (HCT) for a hematologic malignancy. To do so, we conducted a retrospective analysis of 3884 survivors of HCT for hematologic malignancy in the Center of International Blood and Marrow Transplant Research database. We conducted a landmark analysis at the 2-year post-transplantation date, comparing first SN and NM-LE in survivors with and without cGVHD. The cumulative incidence (CuI) of SN and NM-LE were estimated through 10 years post-HCT in both groups, with death or disease relapse as a competing risk. Cox proportional hazards models were used to evaluate the associations of cGVHD and its related characteristics with the development of SN and NM-LE. The estimated 10-year CuI of SN in patients with GVHD (n=2669) and patients without cGVHD (n=1215) was 15% (95% confidence interval [CI], 14% to 17%) versus 9% (7.2% to 11%) (P < .001). cGVHD by 2 years post-HCT was independently associated with SN (hazard ratio [HR], 1.94; 95% CI, 1.53 to 2.46; P < .0001) with a standardized incidence ratio of 3.2 (95% CI, 2.9 to 3.5; P < .0001). Increasing severity of cGVHD was associated with an increased risk of SN. The estimated 10-year CuI of first NM-LE in patients with and without cGVHD was 28 (95% CI, 26% to 30%) versus 13% (95% CI, 11% to 15%) (P < .001). cGVHD by 2 years post-HCT was independently associated with NM-LE (HR, 2.23; 95% CI, 1.81 to 2.76; P < .0001). Multivariate analysis of cGVHD-related factors showed that increasing severity of cGVHD, extensive grade, having both mucocutaneous and visceral involvement, and receiving cGVHD treatment for >12 months were associated with the greatest magnitude of risk for NM-LE. cGVHD was closely associated with both SN and NM-LE in adult survivors of HCT for hematologic malignancy. Patients identified as having more severe involvement and both mucocutaneous and visceral organ involvement may warrant enhanced monitoring and screening for SNs and NM-LEs. However, caution is warranted when interpreting these results, as patients with cGVHD may have more vigilant post-transplantation health care and surveillance for late effects.

Association of Self-Reported COVID-19 Vaccination Status with COVID-19 Infection among Adult Long-Term Hematopoietic Cell Transplantation Survivors

Hematopoietic cell transplantation (HCT) recipients experience significant morbidity and mortality from coronavirus disease 19 (COVID-19) infection. Data are limited regarding long-term HCT survivors' uptake of and experiences with COVID-19 vaccination and infection. This study aimed to characterize COVID-19 vaccination uptake, use of other prevention measures, and COVID-19 infection outcomes in adult HCT recipients at our institution. Between July 1, 2021, and June 30, 2022, long-term adult HCT survivors were surveyed regarding overall health, chronic graft-versus-host (cGVHD) status, and experiences with COVID-19 vaccinations, prevention measures, and infections. Patients reported COVID-19 vaccination status, vaccine-related adverse effects, use of nonpharmaceutical prevention measures, and infections. Comparisons by response and vaccination status were performed using the chi-square test and Fisher exact test for categorical variables and the Kruskal-Wallis test for continuous variables. Of 4758 adult HCT survivors who underwent HCT between 1971 and 2021 and consented to participate in annual surveys, 1719 (36%) completed the COVID-19 module, and 1598 of 1705 (94%) reported receiving ≥1 dose of COVID-19 vaccine. Severe vaccine-related adverse effects were infrequent (5%). Among respondents receiving an mRNA vaccine, completion of doses according to the Centers for Disease Control and Prevention's vaccine recommendations at the time of survey return was 2 doses in 675 of 759 (89%), 3 doses in 610 of 778 (78%), and 4 doses in 26 of 55 (47%). Two hundred fifty respondents (15%) reported COVID-19 infection; 25 (10%) required hospitalization. Vaccinated respondents reported significantly higher uptake of household vaccination (1284 of 1404 [91%] versus 18 of 88 [20%]; P < .001) and the use of nonpharmaceutical interventions (P < .001). Among those vaccinated prior to infection, vaccinated respondents were significantly less likely to have contracted COVID-19 (85 of 1480 [6%] versus 130 of 190 [68%]; P < .001), as were their household members (149 of 1451 [10%] versus 85 of 185 [46%]; P < .001). Receipt of additional COVID-19 vaccine doses beyond the first dose was associated with a reduced risk of COVID-19 infection (odds ratio, .63; 95% confidence interval, .47 to .85; P = .002). Vaccination was well tolerated and associated with a lower risk of COVID-19 infection among HCT survivors and their household contacts. Vaccination and booster doses should be encouraged as part of a multifaceted approach in this high-risk population.

Health-Related Quality of Life Outcomes in Older Hematopoietic Cell Transplantation Survivors

The use of hematopoietic cell transplantation (HCT) has been increasing in older patients. However, the levels if distress, psychosocial functioning, and health-related quality of life (HRQOL) among older HCT survivors remains largely unknown. In this secondary analysis using data from 2 randomized controlled trials, we analyzed baseline Cancer and Treatment Distress (CTXD) and Confidence In Survivorship Information (CSI) surveys of HCT survivors who were age ≥60 years at the time of transplantation and alive and disease-free ≥1 year post-autologous or -allogeneic HCT. We analyzed associations of these parameters with the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the 12-Item Short Form Survey (SF-12) and a healthcare adherence (HCA) scale, after adjusting for transplantation and patient demographic factors. A total of 567 patients were included. The median patient age at HCT was 65 years, and 68% of the patients underwent autologous HCT. The median CTXD score was .7 (mild), and the greatest distress was reported in the "health burden" subscale. The median CSI score was 1.4 (moderate-high), with the lowest confidence reported in the "late effects" subscale. We found negative Spearman correlations between CTXD score and SF-12 PCS (P=-.59) and MCS (P=-.54) and positive Spearman correlations between CSI score and SF-12 PCS (P=.23) and MCS (P=.30). The median HCA scale score was high at .8. Male sex, autologous HCT, increased distress level, and worse CSI score were associated with lower use of preventive care. Older survivors experienced a low level of distress and moderate-high level of CSI at ≥1 year post-HCT. As lower distress and higher CSI were associated with improved HRQOL and optimized preventive HCA, CTXD/CSI measures can be used to individualize the care of older adult HCT survivors.

Self-Reported Experiences of Adult Hematopoietic Cell Transplantation Survivors with COVID-19 Vaccination and Infection

BACKGROUND Hematopoietic cell transplantation (HCT) survivors are at an increased risk of COVID-19 infection and complications. There are scant data for HCT recipients regarding compliance and experiences with COVID-19 vaccination or uptake of other prevention strategies. COVID infection rate data by vaccination status are also lacking in this population. We surveyed a long-term HCT survivor population to characterize the use of COVID-19 vaccination, other precautionary measures, and COVID-19 outcomes. METHODS As part of Fred Hutchinson Cancer Center's follow up of HCT recipients, we administer an annual survey regarding health status, HCT follow up, and chronic GVHD (cGVHD) status including immunosuppressive treatment. We analyzed surveys sent to adults between 7/1/21 and 5/31/22 that included additional questions about COVID-19 infection, prevention measures, and vaccinations. Comparisons by response and vaccination status were performed using the Chi-square test and Fisher's exact test for categorical variables and the Kruskal-Wallis test for continuous variables. RESULTS Of 4758 survivors who underwent HCT from 1971-2020 and consented to receive annual surveys, 1939 (42%) answered the survey and 1572 (33%) answered the COVID-19 questions. Among 1559 respondents who reported their vaccination status, 1456 (93%) received ≥1 dose of COVID vaccine, the majority of whom (1358/1456, 93%) received only mRNA vaccine. Of 1442 patients who received ≥1 dose of vaccine and who provided vaccination information, 1363 (95%) received 2 doses, 808 (56%) received 3 doses, and 115 (8%) received 4 doses. In univariate analysis, older age (p < 0.001), work status (p = 0.005), and current cancer (p = 0.01) were significantly associated with being vaccinated (Table 1). 1254/1344 (93%) non-Hispanic White patients, 107/108 (99%) non-Hispanic/non-White patients, and 31/37 (84%) of Hispanic/Latino patients reported receipt of ≥1 dose of vaccine. Presence of cGVHD, chronic medical conditions, autologous vs. allogeneic transplant, sex, and time since transplant were not associated with vaccination status. Severe adverse effects after vaccination were reported by 66 (4%) respondents (Figure 1). Among 108 vaccinated patients with cGVHD, 96 (89%) did not report any changes in their cGVHD symptoms after vaccination; 12 (11%) reported worsening symptoms. The most common reasons for declining vaccination in unvaccinated patients (n = 103) were the rapidity of vaccine development (70%), side effects (70%), and lack of testing in HCT recipients (53%) as the most common reasons for declining vaccination. Among survey respondents, 212/1564 (14%) reported having a COVID infection, with 55% (114/206) reporting moderate or severe symptoms and 10% (21/204) requiring hospitalization; 10% (20/204) reported "long-COVID." Of 142 vaccinated patients who developed a COVID infection and whose vaccination and infection dates were available, 56% (n = 79) received their first doses of COVID vaccine after COVID infection. Vaccinated patients (5% vs. 68%, p < 0.001) and their household members (10% vs. 45%, p < 0.001) were significantly less likely to have contracted COVID. Higher number of vaccination doses was significantly associated with reduced risk of COVID infection (p < 0.001) but not disease severity. Among the patients who had COVID, there were no significant differences in disease severity, duration, or hospitalization between those who were and were not vaccinated prior to COVID infection. Vaccinated patients took significantly more precautions against COVID than unvaccinated patients (n = 103) both during (7/1/21-2/28/22: median of 5 vs. 2, p < 0.001) and after (3/1/22-5/31/22: median of 4 vs. 1, p < 0.001) the CDC mask mandate was in effect. Vaccination of household contacts was more frequently reported by vaccinated than unvaccinated patients (82% vs. 45%, p < 0.001). CONCLUSION The majority of survey respondents received ≥1 dose of COVID vaccine, and most reported minimal to no adverse effects. The majority of patients with cGVHD did not experience any worsening symptoms. COVID infection was reported by 14% of respondents and was more common in unvaccinated recipient households than vaccinated households. Vaccinated patients reported greater use of precautionary measures, including household vaccination. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence and Determinants of Return to Work as a Patient-Centered Outcome in Survivors of Hematopoietic Cell Transplantation.

Employment is an important indicator of health and functional recovery for hematopoietic cell transplantation (HCT) survivors and has significant social and economic impacts. Cancer survivors treated with conventional non-HCT therapy are known to be at a higher risk of unemployment or not returning to work after completion of therapy compared with the control population. However, the literature on return-to-work challenges among HCT survivors remains limited. Here we summarize the evidence on prevalence and determinants of return-to-work challenges among HCT survivors using previously published literature. Findings from previously published research show that return to work or unemployment is a major concern among HCT survivors, especially for allogeneic HCT recipients, and prior studies have identified several modifiable risk factors associated with it. Survivors' post-HCT employment status is significantly associated with quality of life, impacting physical, emotional, social, and financial aspects of their lives. We also highlight the gaps in current knowledge such as limited information on employment outcomes of childhood, adolescent, and young adult HCT survivors; work-related challenges among employed HCT survivors; consequences of work-related challenges; and interventions to improve return to work among HCT survivors. Findings highlighted in this review make a strong case of a multidisciplinary return-to-work support for HCT survivors to properly address their needs.

Exercise training and NR supplementation to improve muscle mass and fitness in adolescent and young adult hematopoietic cell transplant survivors: a randomized controlled trial {1}

BackgroundAdvances in hematopoietic cell transplantation (HCT) have led to marked improvements in survival. However, adolescents and young adults (AYAs) who undergo HCT are at high risk of developing sarcopenia (loss of skeletal muscle mass) due to the impact of HCT-related exposures on the developing musculoskeletal system. HCT survivors who have sarcopenia also have excess lifetime risk of non-relapse mortality. Therefore, interventions that increase skeletal muscle mass, metabolism, strength, and function are needed to improve health in AYA HCT survivors. Skeletal muscle is highly reliant on mitochondrial energy production, as reflected by oxidative phosphorylation (OXPHOS) capacity. Exercise is one approach to target skeletal muscle mitochondrial OXPHOS, and in turn improve muscle function and strength. Another approach is to use “exercise enhancers”, such as nicotinamide riboside (NR), a safe and well-tolerated precursor of nicotinamide adenine dinucleotide (NAD+), a cofactor that in turn impacts muscle energy production. Interventions combining exercise with exercise enhancers like NR hold promise, but have not yet been rigorously tested in AYA HCT survivors.Methods/designWe will perform a randomized controlled trial testing 16 weeks of in-home aerobic and resistance exercise and NR in AYA HCT survivors, with a primary outcome of muscle strength via dynamometry and a key secondary outcome of cardiovascular fitness via cardiopulmonary exercise testing. We will also test the effects of these interventions on i) muscle mass via dual energy x-ray absorptiometry; ii) muscle mitochondrial OXPHOS via an innovative non-invasive MRI-based technique, and iii) circulating correlates of NAD+ metabolism via metabolomics. Eighty AYAs (ages 15-30y) will be recruited 6–24 months post-HCT and randomized to 1 of 4 arms: exercise + NR, exercise alone, NR alone, or control. Outcomes will be collected at baseline and after the 16-week intervention.DiscussionWe expect that exercise with NR will produce larger changes than exercise alone in key outcomes, and that changes will be mediated by increases in muscle OXPHOS. We will apply the insights gained from this trial to develop individualized, evidence-supported precision initiatives that will reduce chronic disease burden in high-risk cancer survivors.Trial registrationClinicalTrials.gov, NCT05194397. Registered January 18, 2022, https://clinicaltrials.gov/ct2/show/NCT05194397 {2a}.

Long-term patient-reported neurocognitive outcomes in adult survivors of hematopoietic cell transplant

AbstractSurvivors of hematopoietic cell transplant (HCT) are at risk for neurocognitive impairments, which can negatively affect quality of life. Given limited studies, we aimed to describe the neurocognitive outcomes in a cohort of long-term adult HCT survivors. Eligible survivors (age ≥21 years at HCT and alive ≥2 years following HCT) completed a 60-question survey of neurocognitive function and quality of life, which included the Neuro-Quality of Life Cognitive Function Short Form (Neuro-QoL) and the Childhood Cancer Survivor Study Neurocognitive Questionnaire (NCQ). Analyses of risk factors included univariate comparisons and multivariable logistic regression. Survivors (n = 1861, 47.7% female, 65.6% allogeneic HCT) were surveyed at a median age of 64.2 years (interquartile range [IQR], 56.8-70.5) and a median 12.0 years (IQR, 6.0-21.0) from HCT. Survivors reported average Neuro-QoL scores (50.0 allogeneic; 49.2 autologous survivors) compared with an expected mean of 50 in the general population. On the NCQ, 17.4% to 31.2% of survivors reported impairments (Z-score >1.28) in task efficiency, memory, emotional regulation, or organization, compared with an expected 10% in the general population (all P < .01). In multivariable regression analyses, impaired Neuro-QoL (T-score <40) was independently associated with hearing issues (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.46-3.10) and sleep impairment (OR, 4.41; 95% CI, 2.80-6.94) among allogeneic survivors, with comparable associations in autologous survivors. Overall, long-term adult HCT survivors reported average cognitive quality of life compared with the general population. Subsets of survivors with hearing issues and sleep impairments were more likely to report lower quality of life and impaired neurocognitive function, which may facilitate targeted monitoring or interventions following HCT.

Feasibility and acceptability of a home-based resistance training intervention in adolescent and young adult hematopoietic cell transplant survivors.

Adolescent and young adult (AYA) hematopoietic cell transplantation (HCT) survivors are at increased risk of metabolic syndrome and lean body mass (LBM) deficits. Resistance training (RT) is a potential intervention to improve LBM, metabolic fitness, and reduce risk of cardiovascular disease. Eligible participants ages 13-39years, 80-120days post-HCT, transfusion independent, and prednisone dose ≤1mg/kg/day were approached. Baseline assessments of body composition (DXA), anthropometrics, and strength testing were completed and participants were taught a 12-week, home-based RT intervention with weekly remote coaching. Follow-up assessments were at day +200 (FU1) and +365 post-HCT (FU2). Feasibility targets were (a) 60% enrollment of approached patients, (b) 80% completion of weekly phone calls, and (c) 80% completion of the RT intervention and FU1 assessments. Acceptability was based on positive responses in qualitative interviews. Twenty of 31 (65%) eligible AYAs enrolled. Three participants failed to complete baseline measurements (2=scheduling barriers, 1=passive refusal) and four participants who completed baseline assessments did not receive the intervention (1=medical reasons, 2=no longer interested). Of those who completed baseline assessments, 13 received the intervention, completed 88.5% of coaching calls, and 11 (65%) completed FU1. LBM (kg) increased or remained unchanged in nine of nine participants with complete body composition data at FU1 (mean 1.1kg; 95%CI: 0.4, 1.9). All participants who completed FU1 reported they would recommend the intervention to an AYA HCT survivor. A home-based RT intervention in AYA HCT survivors early post HCT is both feasible and acceptable and may maintain or increase LBM.

458 - Feasibility of a Home-Based Resistance Training Intervention in Adolescent and Young Adult Hematopoietic Cell Transplant Survivors

458 - Feasibility of a Home-Based Resistance Training Intervention in Adolescent and Young Adult Hematopoietic Cell Transplant Survivors

Yoga for Cancer-Related Fatigue in Survivors of Hematopoietic Cell Transplantation: A Feasibility Study

ContextCancer-related fatigue (CRF) is one of the most common symptoms experienced by cancer patients after hematopoietic cell transplantation (HCT). Yoga is an approach with supportive evidence to improve CRF in different cancer populations, but to our knowledge, it has not been tested in an adult HCT population. ObjectivesThe aim of this study was to evaluate the feasibility of a yoga intervention offered to adult HCT survivors with moderate-to-severe CRF. MethodsThis feasibility study used a single-arm, pretest-posttest design. Adult HCT survivors were enrolled in a six-week restorative yoga intervention that consisted of a one-hour once-weekly class with twice-weekly home practice using a DVD. ResultsTwenty participants (13 women and seven men) enrolled in this study with a mean age of 51 years (SD = 12.5). The sample consisted of 19 allogeneic HCT survivors, seven of whom had a history of acute graft-vs.-host disease (GVHD), six with active, extensive chronic GVHD, and one autologous HCT survivor. The accrual acceptance rate was 23.2% (20/86 HCT survivors) and retention rate was 60% (12/20). Overall adherence was 45.4%. No adverse events were reported. ConclusionThe results of this study suggest that a restorative yoga intervention in adult HCT survivors is safe and feasible. The incidence of GVHD may have impacted adherence. Strategies to improve accrual acceptance, retention, and adherence are needed.

Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors: A Report from the Center for International Blood and Marrow Transplant Research.

Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.

Thyroid dysfunction in adult hematopoietic cell transplant survivors: risks and outcomes.

The incidence and risk factors for thyroid disorders among adult survivors of allogeneic hematopoietic stem cell transplantation (alloHCT) is not well known. This study evaluated incidence and risk factors of thyroid dysfunction in 259 adult alloHCT recipients who had survived for 2 years or more after transplant. Median follow-up was 4.6 years (range; 2.3 to 15.4 years). The 5-year cumulative incidence of thyroid dysfunction was 30.5% (79 of 259 patients). Majority of thyroid abnormalities were observed beyond 2 years after alloHCT. Subclinical hypothyroidism was the most common thyroid abnormalities accounting for 89% of cases (71 patients). Among these, treatment with thyroid replacement was eventually started in 44% (31 patients). Based on the multivariate analysis, thyroid abnormality was more likely in patients who received high-dose (≥12 Gy) total body irradiation (TBI)-based conditioning regimen compare to low-dose TBI-based (≤500 cGy) and non-TBI-conditioning regimen (p = 0.032). This risk was further augmented directly proportional with the time from alloHCT. These data identify high-dose TBI-conditioning regimen as a risk factor for thyroid dysfunction in adult recipients of alloHCT.

Religious/Spiritual Struggle in Young Adult Hematopoietic Cell Transplant Survivors.

This study describes the prevalence of religious and/or spiritual (R/S) struggle in long-term young adult (YA) survivors following hematopoietic cell transplantation (HCT) as well as existential concerns (EC), social support, and demographic, medical, and emotional correlates of R/S struggle. Data were collected as part of an annual survey of survivors of HCT aged 18-39 years at survey completion; age at HCT was 1-39 years. Study measures included measures of R/S struggle (defined as any non-zero response on the negative religious coping subscale from Brief RCOPE), quality of life (QOL), and depression. Factors associated with R/S struggle were identified using multivariable logistic regression models. Fifty-two of the 172 respondents (30%), who ranged from less than a year to 33 years after HCT, had some R/S struggle. In bivariate analysis, depression was associated with R/S struggle. In a multivariable logistic regression model, individuals with greater EC were nearly five times more likely to report R/S struggle. R/S struggle was not associated with age at transplant, time since transplant, gender, race, R/S self-identification, or medical variables. R/S struggle is common among YA HCT survivors, even many years after HCT. There is a strong correlation between EC and R/S struggle. Given the prevalence of R/S struggle and its associations with EC, survivors should be screened and referred to professionals with expertise in EC and R/S struggle as appropriate. Further study is needed to determine longitudinal trajectory, impact of struggle intensity, causal relationships, and effects of R/S struggle on health, mood, and QOL for YA HCT survivors.

PROMIS measures can be used to assess symptoms and function in long-term hematopoietic cell transplantation survivors.

Patient-reported outcomes for hematopoietic cell transplantation (HCT) survivors are well characterized with established measures; however, there is little experience with the new, freely available Patient-Reported Outcomes Measurement Information System (PROMIS) measures in this population. The aim of this study was to compare the performance of the PROMIS measures in the HCT setting with the performance of the commonly used 36-Item Short Form Health Survey (SF-36). Adult HCT survivors from the Fred Hutchinson Cancer Research Center (n = 4446) were mailed a survey that included the following as part of an annual follow-up survey: the Patient-Reported Outcomes Measurement Information System-Global Health (PROMIS-GH; 10 questions), the 29-Item Patient-Reported Outcomes Measurement Information System Profile (PROMIS-29), and the SF-36. Both the SF-36 and PROMIS measures were available for 1634 HCT recipients (503 autologous recipients and 1131 allogeneic recipients). The overall response rate was 46%. The median time after transplantation for allogeneic and autologous recipients was 12.0 years (range, 0.4-44.1 years) and 6.1 years (range, 0.4-30.1 years), respectively. With the SF-36 or PROMIS-GH, overall physical functioning was somewhat lower in comparison with the general population, but mental functioning was similar. Component and domain scores with similar contents were strongly correlated by Pearson correlation coefficients: the Global Health-Physical and SF-36 Physical Component Summary scores for autologous (r = 0.82) and allogeneic recipients (r = 0.83) and the PROMIS-29 and SF-36 physical function, pain, and vitality/fatigue scores for allogeneic (0.87, -0.82, and -0.82, respectively) and autologous recipients (0.84, -0.82, and -0.81, respectively). The correlation between the Global Health-Mental and SF-36 Mental Component Summary scores was lower (0.70 for autologous recipients and 0.72 for allogeneic recipients). Physical and mental symptoms and function in autologous and allogeneic HCT survivors can be adequately assessed with PROMIS-29 and PROMIS-GH. Cancer 2018;124:841-9. © 2017 American Cancer Society.

Ascertainment of Unmet Needs and Participation in Health Maintenance and Screening of Adult Hematopoietic Cell Transplantation Survivors Followed in a Formal Survivorship Program

This study aimed to ascertain unmet needs in autologous and allogeneic hematopoietic cell transplantation (HCT) recipients actively followed in an established long-term survivorship clinic at Roswell Park Cancer Institute from 2006 to 2012. The Survivor Unmet Needs Survey (SUNS) was mailed to 209 eligible patients and returned by 110 (53% participation rate). SUNS includes 89 items covering 5 domains: Emotional Health, Access and Continuity of Care, Relationships, Financial Concerns, and Information. The top 5 specific unmet needs for autologous HCT patients were inability to set future goals/long-term plans, changes in appearance, bad memory/lacking focus, losing confidence in abilities, and paying household or other bills. For allogeneic HCT patients these 5 unmet needs were tied at 21% of respondents: ability to earn money, pay bills, feeling tired, feeling depressed, and dealing with others' expectations of “returning to normal.” The top 5 needs reported by females were all from the emotional health domain, whereas males reported financial domain unmet needs. Self-reported participation in health maintenance and screening tests varied greatly from 88% of patients having routine annual bloodwork to 13% of patients having an exercise stress test in the past year. Our findings demonstrate unmet needs in emotional health and financial burden in HCT survivors and variable compliance with survivorship screening.

Resilience, health, and quality of life among long-term survivors of hematopoietic cell transplantation.

Low patient-reported resilience is associated with an ongoing risk of poor health and psychosocial outcomes. Using a large cross-sectional sample of survivors of hematopoietic cell transplantation (HCT), this study explored associations between patient-reported resilience, psychological distress, posttraumatic growth, and health-related quality of life. Between July 1, 2013 and June 30, 2014, the annual Fred Hutchinson Cancer Research Center (FHCRC) posttransplant survivorship survey queried patient-reported health and functional status and included instruments assessing psychosocial outcomes: the 10-item Connor-Davidson Resilience Scale, the Posttraumatic Growth Inventory, the Cancer and Treatment Distress measure, and the 12-item Medical Outcomes Study Short Form quality-of-life scale. Multivariate linear and logistic regression models included demographic and health covariates extracted from the FHCRC research database. Among 4643 adult survivors of HCT, 1823 (39%) responded after a single mailing and subsequent reminder letter. The participants' median age was 59 years (interquartile range [IQR], 50-66 years); 52.5% were male, and most were non-Hispanic white. The median time since HCT was 9 years (IQR, 3-18 years). Lower patient-reported resilience was associated with chronic graft-versus-host disease of higher severity, lower performance scores, missing work because of health, and permanent disability (all P < .0001). After adjustments for demographic and health characteristics, patients reporting low resilience scores had higher odds of having psychological distress (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.1-4.3) and being in the lowest quartile for mental health-related quality of life (OR, 5.9; 95% CI, 4.4-8.0). Patient-reported resilience is independently associated with health and psychosocial outcomes. Future studies must determine whether interventions can bolster resilience and improve survivorship outcomes.

Factors Associated with Adherence to Preventive Care Practices among Hematopoietic Cell Transplantation Survivors

Preventive care guidelines are available for hematopoietic cell transplantation (HCT) survivors. We assessed adherence to these guidelines and examined factors associated with lower adherence. A questionnaire was mailed to adult HCT survivors to collect information regarding survivor health, adherence to recommended guidelines, and financial concerns. Multivariate models identified patient and transplant characteristics associated with lower adherence. Of the 3066 survivors at >2 years after HCT, 1549 (51%) responded. The median age of the respondents was 54.5 years, and the median adherence to recommended preventive care based on age- and sex-specific recommendations was 75%. Lower adherence was associated with autologous HCT, concerns about medical costs, non-white race, male sex, lower physical functioning, absence of chronic graft-versus-host disease, longer time since HCT, and poor knowledge of recommended tests. Although 98% of the respondents had medical insurance, 26% expressed concerns about medical costs and reported efforts to limit medical costs. A concern about medical costs was associated with female sex, age <65 years, absence of chronic graft-versus-host disease, and low physical and mental functional status. Future efforts to improve adherence should address concerns about medical costs and lack of knowledge, two major modifiable predictors of lower adherence to preventive care practices in HCT survivors.

Long-Term 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)

AbstractAbstract 217 Introduction:HCT is used with curative intent in children with cancer at risk for relapse. Improvements in transplantation strategies have contributed to increments in survival approximating 10% per decade. Adult HCT survivors are at increased risk for chronic health conditions (Sun, Blood 2010). The magnitude of risk of these conditions in childhood HCT survivors compared with the general population is not defined. Furthermore, while children treated with conventional therapy carry a substantial burden of morbidity (Oeffinger, N Engl J Med 2006), little data exists regarding the added impact of HCT-related conditioning and GvHD on the prevalence of chronic health conditions and functional status. Methods:Participants were drawn from two studies: BMTSS and CCSS. BMTSS examined long-term outcomes in individuals undergoing HCT between 1976 and 1998 at City of Hope or University of Minnesota. Participants were ≤21 years of age at diagnosis of AML, ALL, HL, and NHL, had survived at least 5 yrs from primary diagnosis and 2 yrs from myeloablative HCT. CCSS is a multi-institutional cohort of five-year survivors of childhood cancer diagnosed between 1970 and 1986, and their siblings. For the current study, participation was limited to those treated conventionally with the same diagnoses as BMTSS. Participants for both studies had completed a questionnaire covering the following areas: presence of physical health conditions (endocrinopathies; central nervous system compromise; cardiopulmonary dysfunction; gastrointestinal sequelae; musculoskeletal abnormalities; and subsequent malignancies); chronic GvHD (BMTSS); and sociodemographics. Responses obtained from BMTSS were compared to conventionally treated childhood cancer survivors and sibling controls enrolled in CCSS. Chronic physical health conditions were graded using CTCAE v 3.0 (grade 1–4, ranging from mild to life-threatening/ disabling). Relative risk regression was used to identify risk of health conditions (RR) and 95% confidence interval (CI). Results:The current study included 145 BMTSS participants, 4,020 siblings, and 7,207 CCSS cancer survivors. Median age at participation – BMTSS: 24 yrs; childhood cancer survivors: 24.6 yrs; siblings: 26.6; time from diagnosis – BMTSS: 11.9 yrs; CCSS: 15.6 yrs. 79.3% of BMTSS participants reported at least one condition (grades 1–4); 59.3% multiple (≥2); and 25.5% severe or life-threatening conditions (grade 3–4). Prevalence and severity of these conditions was significantly greater for BMTSS when compared with cancer survivors or siblings (Figure). BMTSS vs. Siblings: After adjustment for age at questionnaire, gender, and ethnicity, BMTSS participants were significantly more likely than sibling controls to report chronic health conditions: grades 1–4: RR=2.7 (95% CI, 2.4–3.0, p<0.01); grades 3–4: RR=6.4 (4.6-8.8, p<0.01); multiple conditions: RR=5.9 (5.0-7.0, p<0.01). In addition, BMTSS participants were significantly more likely to report compromised functional status: adverse general health: RR=3.4 (2.1-5.3, p<0.01); activity limitations: RR=6.8 (5.0-9.3, p<0.01); and functional impairment: RR=7.8 (5.1-12.0, p<0.01). BMTSS vs. CCSS cancer survivors: After adjustment for age, follow-up, gender, ethnicity/race, diagnosis, pre-HCT therapeutic exposures (dose-specific chemotherapy, radiation), and treatment era, BMTSS participants were 1.5 (1.3-1.7, p<0.01) times as likely as conventionally treated patients to report a chronic condition; 2.3 (1.5-3.5, p<0.01) times as likely to report severe/ life-threatening conditions; and 2.2 (1.7-2.8, p<0.01) times as likely to report multiple conditions. Allogeneic HCT recipients with a history of chronic GvHD were at a modestly higher risk of reporting multiple chronic health conditions (Table). [Display omitted] RR (95% CI) Grades 1-4RR (95% CI) Grade 3 or 4RR (95% CI) Multiple (≥2) ConditionsConventionally treated (CCSS)1.01.01.0Autologous HCT (BMTSS)1.3 (1.0–1.7)1.7 (0.7–3.9)1.5 (0.9–2.2)Allogeneic HCT, no GvHD (BMTSS)1.5 (1.2–1.7)2.5 (1.6–3.9)2.2 (1.7–2.8)Allogeneic HCT, GvHD (BMTSS)1.7 (1.4–2.0)2.7 (1.3–5.3)2.9 (2.1–3.9) Conclusions:Childhood HCT survivors carry a significantly higher burden of morbidity when compared with the general population, as well as children treated with conventional therapy, providing evidence for a critical need for close monitoring of this high-risk population. Disclosures:No relevant conflicts of interest to declare.