Survivors Of Bone Marrow Transplantation Research Articles

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.

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<0.03). Frail/pre-frail versus non-frail survivors had a higher p16INK4a expression (p-value<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<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 > 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 >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.

Severe, life-threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood.

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

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.

Immature Testicular Tissue Engineered from Weaned Mice to Adults for Prepubertal Fertility Preservation-An In Vivo Translational Study.

Male pediatric survivors of cancers and bone marrow transplantation often require adjuvant chemoradiation therapy that may be gonadotoxic. The optimal methods to preserve fertility in these prepubertal males are still under investigation. This manuscript presents an in vivo experiment which involved transplantation of immature testicular tissues (ITT) from transgenic donor, to wild-type recipient mice. Donors and recipients were age-mismatched (from 20-week-old donors to 3-week-old recipients, and vice versa) and the transplantation sites involved the abdomen, skin of the head, back muscle, and scrotum. The application of poly-l-lactic acid (PLLA) scaffold was also evaluated in age-matched donors and recipients (both 3-weeks-old). To quantitively evaluate the process of spermatogenesis after ITT transplantation and scaffold application, bioluminescence imaging (BLI) was employed. Our result showed that ITT from 3-week-old mice had the best potential for spermatogenesis, and the optimal transplantation site was in the scrotum. Spermatogenesis was observed in recipient mice up to 51 days after transplantation, and up to the 85th day if scaffold was used. The peak of spermatogenesis occurred between the 42nd and 55th days in the scaffold group. This animal model may serve as a framework for further studies in prepubertal male fertility preservation.

Implementation of a clinic to facilitate the transition from pediatric to adult cancer survivorship care.

e13519 Background: Transitions from pediatric to adult care settings are challenging for adults with a history of complex childhood illness such as cancer. We developed a new clinical model to support young adult survivors of leukemia and bone marrow transplant (BMT) with transitioning from pediatric to adult focused survivorship care. Methods: We established the GREAT (Getting Regular Evaluations After Treatment) survivorship clinic as a collaboration between the adolescent/young adult (AYA) cancer program, pediatric oncologists, and specialists in adult hematologic malignancies. New patient appointments consist of two back-to-back visits: (1) a medical survivorship visit with a pediatric oncologist and an oncologist who specializes in hematologic malignancies/BMT to review the treatment history, medical issues, risk of late effects, and surveillance recommendations, and (2) an AYA-focused visit with a nurse practitioner to review fertility, education/career, and psychosocial concerns. Patients receive a treatment summary through the Passport for Care, based on pediatric survivorship guidelines. The clinic team then communicates with the patient’s primary care provider (PCP) or assists the patient with finding a PCP. Results: Since August 2020, we have seen 17 patients (12 telehealth, 5 in-person, 53% male, 47% non-Hispanic white, 41% Hispanic/Latino, 12% Asian). The median age at clinic visit was 28 years (range 24-39) and median time since treatment was 15 years (range 1-29). Patients were referred through the AYA cancer program: 8 had been regularly followed in the pediatric survivorship clinic, 2 had not been seen in pediatric oncology/survivorship for many years, 3 were treated as children but most recently seen by adult oncologists, and 4 were treated by adult oncologists and referred for AYA-specific survivorship care. Twelve (71%) patients had a PCP they see regularly, while 2 did not have a PCP and 3 were not sure. Communication with PCPs consisted of faxing the clinic note and calling the PCP’s office. All PCPs were receptive and expressed interest in receiving survivorship care recommendations; some preferred to order late effects surveillance imaging/labs, while others preferred the GREAT clinic team to do so, illustrating the value of two-way communication. Thirteen (76%) patients participated in post-clinic interviews. All stated they would recommend the clinic to others. Common themes from interviews included understanding more about their past treatment and having greater confidence managing their health. Conclusions: The model for facilitating care transitions was highly regarded by young adult cancer survivors and highlights opportunities for improving self-management and care coordination. Future directions include expanding to more cancer types, addressing barriers to primary care follow-up, and exploring shared care or co-management with PCPs.

Survivors of allogeneic bone marrow transplants in childhood report no significant long-term respiratory symptoms: A single-center analysis over 20years.

Pulmonary toxicity is documented in long-term survivors of allogeneic BMT. No studies have specifically evaluated late pulmonary symptomatology in these patients. 85 long-term pediatric survivors were sent a validated questionnaire of pulmonary symptomatology. Demographic and clinical data were retrospectively collected from the respondents medical records. Response rate was 52.9%. Mean follow-up post-BMT of those who responded was 12.3years. Mean pulmonary symptom scores were low (0.78). There was no significant difference in symptoms between patients who underwent MA conditioning with or without TBI. These results are reassuring that long-term survivors of pediatric BMT have few respiratory symptoms which do not impact on activities of daily living.

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.

Senolytic drugs: from discovery to translation.

Senolytics are a class of drugs that selectively clear senescent cells (SC). The first senolytic drugs Dasatinib, Quercetin, Fisetin and Navitoclax were discovered using a hypothesis‐driven approach. SC accumulate with ageing and at causal sites of multiple chronic disorders, including diseases accounting for the bulk of morbidity, mortality and health expenditures. The most deleterious SC are resistant to apoptosis and have up‐regulation of anti‐apoptotic pathways which defend SC against their own inflammatory senescence‐associated secretory phenotype (SASP), allowing them to survive, despite killing neighbouring cells. Senolytics transiently disable these SCAPs, causing apoptosis of those SC with a tissue‐destructive SASP. Because SC take weeks to reaccumulate, senolytics can be administered intermittently – a ‘hit‐and‐run’ approach. In preclinical models, senolytics delay, prevent or alleviate frailty, cancers and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, haematological, metabolic and skin disorders as well as complications of organ transplantation, radiation and cancer treatment. As anticipated for agents targeting the fundamental ageing mechanisms that are ‘root cause’ contributors to multiple disorders, potential uses of senolytics are protean, potentially alleviating over 40 conditions in preclinical studies, opening a new route for treating age‐related dysfunction and diseases. Early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation and alleviate frailty in humans. Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer’s disease, COVID‐19, osteoarthritis, osteoporosis, eye diseases and bone marrow transplant and childhood cancer survivors are underway or beginning. Until such studies are done, it is too early for senolytics to be used outside of clinical trials.

Primary care utilization and barriers among pediatric cancer and bone marrow transplant survivors.

e22523 Background: The Institute of Medicine (IOM) report on childhood cancer survivorship specified the need to create and evaluate standards and alternative models of care delivery, including collaborative practices between oncologists and primary care physicians (PCP).1 We aimed to examine the utilization of primary care physicians by childhood cancer and bone marrow transplant (BMT) survivors, as well as identify barriers to non-oncology follow-up care. Methods: Survivors and caregivers were recruited from a cancer and bone marrow transplant survivorship clinic at a large Midwestern pediatric hospital. Participants completed a demographic survey and an 8-item semi-structured interview in clinic or online. Results: A total of 472 participants (211 survivors, 259 caregivers, 2 left unanswered) completed the survey (Survivors Mage= 26.11, SD= 7.32). Most participants were Caucasian (89%) and female (58%). Only 57 (12.3%) survivors received a BMT. There were no significant differences in PCP utilization between BMT survivors and those who did not receive a BMT, t(448) = -.519, p = .604. In addition, there were no significant group differences in PCP utilization between oncological and hematologic survivors, t(387) = 1.144, p = .253. Most survivors (87%) had a PCP, but 43% sought care for ill visits only. Survivors most commonly chose their PCP through referral from family or friends (45%), with only 4% obtaining a recommendation from their oncology provider. Top reasons for not having a PCP included being unsure who to see (52%), lack of insurance (20%), and not perceiving a need for a PCP (18%). In a logistic regression, greater annual family income ( β= .209, p&lt; .001) and having health insurance ( β= .161, p&lt; .01) were predictive of having a PCP. The frequency of PCP visits was also positively correlated with annual family income ( r= .13, p= .014). Conclusions: While most survivors had a PCP, higher income and insurance coverage were important predictors of having a PCP. There is a clear need for education and formal transition programs to primary care, as survivors and their family identified the need for guidance in choosing a PCP. Stronger partnerships between oncology and primary care providers may improve surveillance and outcomes for these survivors. 1. Blaauwbrock R, Zwart, N., Bouma, M., Meyboom-de Jung, B., Kamps, W., &amp; A. Postma. The willingness of general practitioners to be involved in the follow up of adult survivors of childhood cancer. Journal of Cancer Survivors. 2007;1:292-297.

Morbidity burden in survivors of multiple myeloma who underwent autologous transplantation: A Bone Marrow Transplantation Survivor Study.

Autologous blood or bone marrow transplantation (aBMT) is considered the standard of care for patients with multiple myeloma (MM). Significantly improved survival necessitates an understanding of the morbidity burden borne by the growing survivor population. The authors evaluated severe and/or life-threatening chronic health conditions (CHCs) and subsequent neoplasms (SNs) in patients with MM who were treated with aBMT using the Bone Marrow Transplant Survivor Study. A total of 630 study participants had undergone aBMT for MM at 1 of 3 BMT centers, had survived ≥2years after aBMT, and were aged ≥18years at the time of survey completion. Survivors of aBMT identified 289 nearest-age siblings to constitute an unaffected comparison group. Scoring of CHCs was based on version 5 of the National Cancer Institute Common Terminology Criteria for Adverse Events to determine severity (with grade 3 indicating serious and grade 4 indicating life-threatening). The 10-year cumulative incidence of any grade 3 to 4 CHC among survivors of aBMT was 57.6±3.2%. Survivors of MM were found to be at 40% higher odds of developing grade 3 to 4 CHCs when compared with siblings (95% confidence interval [95% CI], 1.0-1.9). Among SNs, 96% were solid tumors, yielding a 10-year cumulative incidence of 13.6%±2.5%. Pre-aBMT exposure to cyclophosphamide (hazard ratio [HR], 3.5; 95% CI, 1.5-8.1) and immunomodulatory drugs (HR, 3.9; 95% CI, 1.5-10.1) were associated with an increased risk of solid tumors. Melanoma (10-year cumulative incidence: 3.3%±1.2%) and squamous cell carcinoma (10-year cumulative incidence: 5.1%±1.8%), were the most common SNs. Pre-aBMT exposure to cyclophosphamide (HR, 6.02; 95% CI, 1.4-26.1) and immunomodulatory drugs (HR, 7.9; 95% CI, 0.9-68.5) was associated with an increased risk of melanoma. The 10-year cumulative incidence of severe and/or life-threatening CHCs was found to approach 60% in long-term survivors of MM, with solid SNs constituting a large morbidity burden. The current study has provided evidence supporting the close monitoring of survivors to manage morbidity.

Self‐endorsed cognitive problems versus objectively assessed cognitive impairment in blood or bone marrow transplantation recipients: A longitudinal study

Cognitive impairment in survivors of blood or bone marrow transplantation (BMT) is well documented. However, to the authors' knowledge, the clinical relevance of self-endorsed cognitive problems and their relation to objectively assessed cognitive impairment is not known. The authors assessed cognitive impairment in 378 BMT recipients (median age, 52.2years, 40% of whom were female and 68% of whom were non-Hispanic white) and 98 healthy controls at 5 predetermined time points: at baseline (before BMT) and at 6months, 1year, 2years, and 3years after BMT. Self-endorsed cognitive problems were evaluated using the Neuropsychological Impairment Scale (NIS) and correlated with a standardized 2-hour battery of objective cognitive testing at each time point. The authors examined the magnitude of difference in self-endorsed cognitive problems between BMT recipients and healthy controls, and the rate of change in scores over time. Multivariable analyses were used to identify clinical and/or demographic variables associated with self-endorsed cognitive problems. The authors also examined the association between cognitive impairment and returning to work after BMT. Compared with healthy controls, BMT recipients endorsed more cognitive problems (P<.001) at all time points, and the rate of change in NIS scores was found to be significantly greater in BMT recipients. Fatigue was associated with greater endorsement of cognitive problems at 1year after BMT (odds ratio, 4.23; 95% CI, 2.1-8.3 [P<.001]). Overall, there was a statistically significant, modest correlation noted between self-endorsed cognitive problems and objective cognitive impairment (range, 0.401-0.445 [P≤.01]). Higher self-endorsed cognitive problems were associated with a 3.7-fold (P=.02) higher odds of not returning to work at 3years after BMT. The results of the current study demonstrated that self-endorsed cognitive problems can help to identify vulnerable patient subpopulations for detailed cognitive assessment and possible cognitive remediation.

Ultrasound is superior to palpation for thyroid cancer detection in high-risk childhood cancer and BMT survivors

Thyroid cancer is a common subsequent malignant neoplasm in childhood cancer survivors (CCS). Patients who received radiotherapy (RT) to the head, neck, upper thorax, or total body irradiation (TBI) are considered to be at risk for subsequent thyroid cancer. Current Children's Oncology Group screening guidelines recommend annual neck palpation. Our objective was to determine if ultrasound (US) is more sensitive and specific than palpation to detect thyroid cancer in high-risk CCS and bone marrow transplant (BMT) survivors. Electronic medical records of patients followed in a longitudinal survivorship clinic from January 1, 2010 to December 31, 2017 were reviewed. Inclusion criteria included history of RT to the head, neck, upper thorax, or TBI for primary therapy or preparation for BMT prior to the age of 20years. Two hundred and twenty-five patients had documented palpation and 144 (64%) also had US evaluation. Mean radiation dose was 28.6Gy. Sixteen of 225 patients (7.1%) developed a subsequent thyroid cancer at a mean of 9.7years from the completion of RT. Sensitivity of US was 100% compared with 12.5% for palpation. US demonstrated higher accuracy, with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.87 versus 0.56 for palpation (P < 0.0001). Routine screening with US was more sensitive than palpation for detection of subsequent thyroid cancer after high-risk RT in CCS and BMT survivors. Screening US may lead to earlier detection of thyroid cancer in this population. Earlier diagnosis has the potential to decrease operative complexity, and earlier definitive therapy reduces the likelihood of metastatic disease.

Pain in older survivors of hematologic malignancies after blood or marrow transplantation: A BMTSS report.

Blood or marrow transplantation (BMT) is increasingly offered to older adults with hematologic malignancies; however, their risk for severe pain is poorly understood. Using the Bone Marrow Transplant Survivor Study, the current study investigated the prevalence and predictors of pain after BMT (allogeneic or autologous) as well as its association with physical performance impairments and frailty. The cohort included 736 patients with hematologic malignancies who underwent BMT at an age≥60years at 1 of 3 transplant centers between 1974 and 2014 and survived ≥2years after BMT; 183 unaffected siblings also participated. Study participants reported on 4 pain domains (nonminor everyday pain, moderate to severe bodily pain, prolonged pain, and moderate to extreme pain interference), and the presence of 1 or more domains was indicative of a severe and/or life-interfering pain composite variable. Overall, 39.4% of the BMT survivors reported severe pain with 2.6-fold greater odds of reporting pain in comparison with sibling controls. Among BMT recipients, those with less education, lower incomes, and active chronic graft-versus-host disease had higher odds of reporting pain. In multivariable analyses, BMT survivors with pain were more likely to have impaired physical performance and were more likely to meet the frailty criteria. BMT survivors reported higher use of pain medications (17.8% vs 9.3%) and opioid pain medications (6.5% vs 2.2%) in comparison with sibling controls. Nearly 40% of older BMT survivors who were followed for a median of 5years after BMT reported pain, and BMT survivors had 2.6-fold higher odds of reporting severe, nonminor or life-interfering pain in comparison with siblings.

ARRHYTHMIA IN BONE MARROW TRANSPLANT: WHY WE SHOULD WORRY

The Bone Marrow Transplant Survivor Study indicates that two-thirds of hematopoietic stem cell transplantation (HSCT) survivors develop a chronic health condition. Arrhythmia has been identified as a complication of HSCT in single-institution reports, but conclusive data at the national level is

Improving Care Transitions in Healthcare: A Human Factors/Ergonomics (HFE) Approach

Delivering safe healthcare often involves multi-disciplinary teams working across multiple locations. Care transitions are required to provide continuity of care and are often fail due to this type of complexity. Care transitions occur in numerous settings, for example: during shift changes, transfer between wards, or during discharge to the patient’s home (WHO Collaborating Centre for Patient Safety Solutions 2007). The aim of the panel will be to discuss different types of care transitions and how HFE can assist in improving patient safety and efficiency of the process. The panel will discuss and share lessons learnt from a range of projects involving care transitions for pediatric trauma care (Woolridge), and barriers and facilitators to follow-up care for bone marrow transplant survivors (Sesto). In addition, the work system elements for care transitions for elective orthopedic patients (Carman), elderly patients after heart failure hospitalization (Holden) and risks to elderly patients’ safe medication management (Gurses) when transitioning from hospital to home will be discussed.

Leveraging the electronic health record (EHR) to support survivorship care planning for bone marrow transplant (BMT) survivors.

57 Background: BMT survivors are underrepresented in survivorship research, yet are at high risk for complications. Practice guidelines are vague, non-BMT clinicians are inadequately informed, and communication between BMT and non-BMT clinicians is inconsistent. Our objective is to develop EHR-integrated survivorship care planning that is user-centered, supports non-BMT clinician and survivor needs, but does not adversely impact clinical workflow. Methods: A multidisciplinary team of clinicians (primary care, oncology, BMT), engineers, and EHR analysts used a systems engineering approach to identify barriers and facilitators to BMT survivorship care planning. The team identified patient data categories to include in BMT survivorship care plan (SCP) templates, as well as examined tasks, technology, workflows and individual roles and responsibilities necessary to support care planning. Results: Facilitators include: potential for EHR to discretely capture individual diagnosis and treatment data to create accurate SCPs addressing survivor and primary care information needs. Barriers are: lack of EHR inter-operability which prevents sharing of patient data outside the BMT center’s EHR system, reliance on manual entry of critical data elements into the SCP (i.e. majority of the 88 patient data categories, identified by the team, are non-discrete in the EHR), inefficient or absent survivorship workflows, lack of resources (including time, dedicated clinical staff, space, SCP content), poorly defined roles and responsibilities for survivorship care provision, and lack of evidence-based BMT survivorship guidelines. Conclusions: Work system barriers impede use of the EHR to support survivorship care planning. Steps to overcome barriers: design discrete fields in the EHR to support patient-level data capture, re-engineer existing workflows to support survivorship care planning, obtain BMT program consensus on SCP content, and evaluate user-centeredness of SCPs. This research has the potential to improve feasibility and sustainability of survivorship care planning activities, resulting in improved communication and care coordination for BMT survivors.

退院後の骨髄移植者が抱える問題に関する基礎調査 : 性生活・社会復帰について

退院後の骨髄移植者が抱える問題に関する基礎調査 : 性生活・社会復帰について