Survivors Of Hematopoietic Stem Cell Transplantation Research Articles

Are cardio-metabolic late-effects modifiable through a low-fat diet in long-term survivors of pediatric allogeneic stem cell transplantation?

Rationale: Increasing survival rates in allogeneic hematopoietic stem cell transplantation (HSCT) has led to an increased focus on the late-effects of the treatment, including early onset metabolic syndrome (MetS). While lifestyle factors such as nutrition play a role in the development of MetS in the general population, total body irradiation (TBI) are a significant risk factor among HSCT-survivors. We have limited insights into the role of dietary factors in this group. The aim of this study was to describe the diet of long term survivors of pediatric HSCT and to explore associations with MetS.

Second Solid Cancers After Hematopoietic Stem Cell Transplantation: Active Surveillance During Long-term Follow-up.

Second Solid Cancers After Hematopoietic Stem Cell Transplantation: Active Surveillance During Long-term Follow-up.

Cardiovascular events among recipients of hematopoietic stem cell transplantation

Abstract Background Allogeneic and autologous hematopoietic stem cell transplantation (HSCT) are potential curative treatments for several hematological malignancies (1). Survival after HSCT has improved over the last decade, but survivors remain at risk for health issues after transplantation. Cardiovascular complications after HSCT are increasingly recognized (2). Cardiovascular diseases may be an important cause of mortality and morbidity in patients after HSCT owing to the toxicities of the cancer therapies; however, the incidence of cardiovascular events (CVEs) in this population has not been completely characterized. The objective of this systematic review is to summarize the evidence on the incidence of CVEs in HSCT recipients. Methods Medline and Embase were searched from inception to December 2020 without language restriction. Two authors independently screened the titles and abstracts. Inclusion criteria were: cohort studies and phase 3 randomized controlled trials that reported CVEs (i.e., heart failure, arrythmias, acute coronary syndrome, and stroke) or cardiovascular death among adults who underwent HSCT for a hematological malignancy. All-cause mortality, relapse-related mortality, and non-relapse-related mortality (NRM) were also collected. Studies in which the follow up period was not started immediately after HSCT were excluded due to the risk of immortal bias. Results Of 8151 nonduplicate articles, 30 studies including 14019 individuals post autologous HSCT, and 22 studies including 31049 individuals post allogeneic HSCT met the inclusion criteria. The cumulative incidence of CVEs in the first 100 days post autologous HSCT was 9% and arrhythmia (i.e., atrial fibrillation) was the most common CVE. In recipients of allogeneic HSCT, the 100-day cumulative incidence of CVEs was 3%, and heart failure (HF) was the most common reported CVE. In recipients of autologous and allogeneic HSCT, cardiovascular death was responsible for 43% and 10% of NRM within 100 days, respectively (Table 1). The incidence of CVEs was 4.96 per 1000-person years (95% CI; 4.21–5.80) in long-term survivors (beyond 100-days) of autologous HSCT, and HF was the most common CVE in this population. In long-term survivors of allogeneic HSCT, the incidence of CVEs was 1.90 per 1000-person years (95% CI: 1.59–2.24). Cardiovascular death was the most frequently reported CVE in long-term survivors of allogeneic HSCT (Table 2). Conclusion CVEs remain a major cause of non relapse morbidity and mortality in recipients of HSCT, especially recipients of autologous HSCT within the first 100 days. Future studies are needed to identify the risk factors for CVEs that are specific to HSCT recipients. Funding Acknowledgement Type of funding sources: None.

Impact of chronic GVHD on QOL assessed by visual analogue scale in pediatric HSCT survivors and differences between raters: a cross-sectional observational study in Japan.

A nationwide cross-sectional survey was conducted in long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT) in childhood to investigate the effect of chronic graft-versus-host disease (cGVHD) on quality of life (QOL) and differences in QOL assessments between raters. QOL was evaluated by a visual analogue scale (VAS). Assessments were compared between the survivor, guardian, and attending pediatrician for those aged 15years or younger, and between the survivor and attending pediatrician for those aged 16years or older. For cGVHD, severity scores were obtained by organ and their association with the VAS score was analyzed. The average pediatrician-rated VAS score was higher than that of other raters for both patient age groups (< 15years and > 16years). By organ, involvement of the skin, digestive organs, and joints in GVHD affected the VAS scores. A high joint score was associated with a low VAS score, and conversely, a high lung score was associated with a low pediatrician-rated VAS score. Our results indicate that differences between raters must be considered when evaluating QOL of HSCT survivors, because patients appeared to experience grater inconvenience and difficulties due to joint GVHD than their pediatricians perceived.

A SMART approach to optimizing delivery of an mHealth intervention among cancer survivors with posttraumatic stress symptoms

Background/aimsMany cancer survivors who received intensive treatment such as hematopoietic stem cell transplantation (HCT) experience posttraumatic stress disorder (PTSD) symptoms. PTSD is associated with lower quality of life and other symptoms that require clinical treatment. The iterative treatment decisions that happen in clinical practice are not adequately represented in traditional randomized controlled trials (RCT) of PTSD treatments. The proposed stepped-care SMART design allows for evaluation of initial response to the Cancer Distress Coach mobile app; adaptive stepped-care interventions; and precision treatment strategies that tailor treatment selection to patient characteristics. Methods/designHCT survivors (N = 400) reporting PTSD symptoms are being recruited at two cancer centers and randomly assigned to: 1) Cancer Distress Coach app or 2) Usual Care. The app includes educational and cognitive behavioral therapy (CBT)-based activities. Four weeks post-randomization, participants re-rate their PTSD symptoms and, based on intervention response, non-responders are re-randomized to receive video-conferenced sessions with a therapist: 3) coaching sessions in using the mobile app; or 4) CBT specific to HCT survivors. Participants complete outcome measures of PTSD, depression, and anxiety after Months 1, 3, and 6. Participant characteristics moderating intervention responses will be examined. ConclusionsThis novel adaptive trial design will afford evidence that furthers knowledge about optimizing PTSD interventions for HCT survivors. To our knowledge, this study is the first SMART design evaluating PTSD symptom management in cancer survivors. If successful, it could be used to optimize treatment among a range of cancer and other trauma survivors.

Barriers and facilitators to the use of survivorship care plans by hematopoietic stem cell transplant survivors and clinicians.

Survivors of hematopoietic stem cell transplants (HSCT) have complex care needs for the remainder of their lives, known as the survivorship period. Survivorship care plans (SCPs) have been proposed to improve care coordination and ultimately survivorship outcomes. We explored the barriers and facilitators of SCP use among HSCT survivors and their clinicians in order to develop more useful SCPs for the HSCT context. Analogous surveys regarding perceived barriers to and facilitators of SCP use based on a sample SCP for a female allogenic HSCT survivor were administered to HSCT survivors and non-transplant oncology and primary care clinicians. Twenty-seven HSCT survivors and 18 clinicians completed the survey. The main barriers to SCP use were lack of awareness of SCP existence, uncertainty regarding where to find SCP, unclear roles and responsibilities among healthcare teams, length of SCP, and difficultly understanding SCPs. The facilitators of SCP use were increased understanding of survivorship care needs, clarified roles and responsibilities of survivors and clinicians, SCPs that are readily available and searchable in electronic health record, increased awareness of SCP existence and provision to all survivors, and if the SCP is survivor-specific and up-to-date. Much of the work regarding SCPs has looked at barriers to creation and provision; however, our study examines factors influencing use of SCPs. By determining the barriers and facilitators surrounding SCP use for HSCT survivors and their clinicians, we can create SCP templates and clinical workflows to optimize SCP use, ideally leading to better outcomes for HSCT survivors.

Assessment of cellular response to mitogens in long-term allogeneic hematopoietic stem cell transplantation survivors.

Infection is one of the major causes of death in hematopoietic stem cell transplantation (HSCT) survivors. Precise assessments of immune function after HSCT will be critical in establishing appropriate treatment and prophylaxis, such as re-vaccination. Although several surrogate markers for prediction of clinical outcomes after HSCT have been proposed, definitive markers of immune reconstitution and data on those markers in long-term survivors are lacking. In this study, cellular response to mitogens was assessed and clinical features associated with a poor response to mitogens were investigated in long-term allogeneic HSCT survivors. Age at transplantation and age at the time of mitogen stimulation test were each identified as significant risk factors for poor response to phytohemagglutinin and concanavalin A, respectively (P < 0.001 each). However, time elapsed since transplantation was not found to be correlated with responsiveness to mitogens in this study. Prospective, in-depth studies on immune reconstitution are needed to establish appropriate prophylaxis against infections after HSCT and a schedule for re-vaccination.

Neurocognitive Impairment After Hematopoietic Stem Cell Transplant for Hematologic Malignancies: Phenotype and Mechanisms

Hematopoietic stem cell transplant (HSCT) plays a central role in the treatment of hematologic cancers. With the increasing survival of patients after HSCT, survivorship issues experienced by this population have become an important outcome. Cognitive impairment is an established sequela of HSCT, with studies to date establishing its presence, associated risk factors, and clinical phenotype. There are multiple potential contributors to cognitive impairment after HSCT. Efforts are ongoing to further characterize its clinical phenotype, associated biomarkers, and biologic underpinnings. A fundamental knowledge of post-HSCT cognitive impairment is of value for all clinicians who interface with this population, and further academic efforts are needed to more fully understand the impact of this cancer treatment on brain health. IMPLICATIONS FOR PRACTICE: As survival outcomes after hematopoietic stem cell transplant (HSCT) improve, an awareness of the post-treatment challenges faced by this population has become central to its care. HSCT can have a sustained and broad impact on brain health, causing cognitive dysfunction, fatigue, disturbed mood, and sleep. In affected patients, autonomy, return to work, relationships, and quality of life may all be affected. A fundamental fluency in this area is important for clinicians interfacing with HSCT survivors, facilitating the identification and management of cognitive dysfunction and concurrent symptom clusters, and stimulating interest in these sequelae as areas for future clinical research.

Metabolic Syndrome in Male Survivors of Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Impact of Total Body Irradiation, Low-Grade Inflammation, and Hypogonadism

Metabolic syndrome (MetS) is a growing concern in survivors of pediatric hematopoietic stem cell transplantation (HSCT), but little is known about the underlying mechanisms. This study aimed to determine the prevalence and clinical presentation of MetS in male long-term survivors of pediatric HSCT and to investigate predisposing factors, including low-grade inflammation, altered fat distribution, and low testosterone levels. We included 98 survivors age 19 to 47 years at a median follow-up of 18 years (range, 8 to 35 years) after pediatric HSCT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence and clinical manifestations of MetS were compared between our cohort and a control group of males from the background population (n=4767). Fat distribution was assessed by android/gynoid ratio from a whole-body dual-energy X-ray absorptiometry scan. Systemic inflammation was evaluated by IL-6 and high-sensitivity C-reactive protein (hsCRP). Serum testosterone levels were measured in morning samples. The prevalence of MetS was 30%, corresponding to the prevalence in the 50- to 80-year-old males from the background population. In individuals with MetS, hyperglycemia was more frequent in the HSCT survivors compared with age-matched controls with MetS (76% versus 20%; P < .001), whereas hypertension was more dominant in the control group with MetS (69% versus 93%; P=.01). In addition, normal or low body mass index was more commonly observed among HSCT survivors with MetS compared with age-matched controls with MetS (41% versus 11%; P=.002). MetS was more often associated with total body irradiation (TBI) compared with chemotherapy regimens (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.2 to 24.4; P=.02), lower testosterone levels (OR, 5.4; 95% CI, 1.3 to 23.6; P=.02), higher IL-6 levels (OR, 1.8; 95% CI, 1.2 to 2.8; P=.004), and higher hsCRP levels (OR, 1.8; 95% CI, 1.3 to 2.6; P < .001) (estimates per 2-fold increase). In addition, an increased android/gynoid (AG) fat ratio was strongly associated with MetS (OR, 2.1; 95% CI, 1.5 to 2.9; P < .001), even though only 7% of patients met the criteria for increased abdominal circumference. Our results indicate an increased risk of MetS in early adulthood after pediatric HSCT. The clinical manifestations differed from those seen in age-matched controls with MetS, indicating different pathophysiology driven by hyperglycemia, altered fat distribution (despite no clinical abdominal obesity), and low-grade inflammation. Risk factors included TBI-based conditioning and low testosterone levels. These results underline the importance of continuous clinical assessment of the cardiometabolic risk profile and stress the presence of important dissimilarities in the pathophysiology of MetS in HSCT survivors compared with the background population.

Social Support Source and Effectiveness Are Associated with Distress Among Hematopoietic Stem Cell Transplant Survivors Experiencing Stress Due to Negative Life Events after Treatment

Hematopoietic stem cell transplant (HSCT) survivors face a variety of stressful challenges in the months and years after treatment including risk for disease relapse, transplant failure, and late effects of treatment; chronic symptoms and complications; and the need to adhere to continuing medical management. Layered on treatment-related challenges are treatment- and non-treatment-related financial, family, work, or other psychosocial strains. Research suggests that these kinds of “life event stressors” can cause psychological distress, which in turn may influence survivors' health behaviors and clinical outcomes. Receiving effective social support from a caregiver has been associated with lower distress (main effects), and the effectiveness of caregiver support could also be an important determinant of whether the support mitigates or “buffers” adverse effects of life event stressors. We applied our Social Support Effectiveness framework to investigate whether: (1) the effectiveness of social support from a partner or non-partner caregiver was associated with survivor distress (main effect); (2) the effectiveness of caregiver support was associated with the association between life event stress and distress among survivors (buffering); and (3) whether buffering effects depended on the source of support (partners versus non-partner caregivers).As part of a larger study, 264 adults who had undergone HSCT 9 months to 3 years previously completed measures of caregiver social support effectiveness (SSE), distress, life event stress, and sociodemographic and medical variables. Life event stress was a count of negative life events experienced in the prior 6 months, measured with a validated scale and scored using recommended procedures. The SSE measure assesses survivors' appraisals of the extent to which social support they receive from their partner or non-partner caregiver generally approximates their needs in terms of its quantity (i.e., it is not too much nor too little) and quality (i.e., it is the right “type” of support, provided skillfully, is not hard to get or is provided without having to ask for it, and does not cause the survivor to feel bad for needing or getting it). SSE is theorized to be a stable feature of support in dyadic relationships (such as those with a partner or family member), with little change over time. Survivors in a committed romantic relationship reported the effectiveness of support received from their partner and those not in a committed relationship reported the effectiveness of support received from their most important transplant caregiver. Hierarchal linear regression was used to evaluate a three-way interaction between life event stress, caregiver SSE, and source of support (partner versus non-partner caregiver) on distress in these cross-sectional data.In models controlling for covariates, main effects revealed that having greater life event stress (B=0.04; 95% CI 0.04, 0.05; p <0.001) and receiving less effective caregiver support (B=-0.01; 95% CI -0.01, -0.003; p <0.001) were independently associated with greater survivor distress. These main effects were qualified by a 3-way interaction of life event stress, caregiver SSE, and source of support (B=-0.003; CI:-0.004, -0.002; p <0.001). When support was provided by a partner caregiver, higher life event stress was associated with greater distress when partner SSE was low (B=0.03, SE=0.01, p=0.02). There was no association between life event stress and distress when partner SSE was average (B=0.04, SE=0.01, p=0.26) or high (B=-0.003, SE=0.01, p=0.87). Among non-partnered cancer survivors, there was a positive association between life event stress and distress regardless of non-partner caregiver SSE. Thus, effective support from a partner caregiver buffered adverse effects of life event stress on survivor distress, but this salutary effect was not observed for non-partner caregivers.Our findings are consistent with evidence showing that the effectiveness of caregiver support is an important correlate of distress after HSCT. They extend that work by showing that effective support from a partner caregiver (but not a non-partner caregiver) can mitigate or “buffer” adverse effects of negative life events experienced after HSCT. Findings highlight a need for additional research among HSCT recipients who rely on caregivers other than a partner. DisclosuresNo relevant conflicts of interest to declare.

Patient Interest in and Feasibility of a Mobile Health App to Support Patients Undergoing Hematopoietic Stem Cell Transplantation

Introduction: Mobile health applications (mHealth apps) have the potential to enhance patient-provider communication and assessment through active and passive evaluation and tracking. Early detection may lead to earlier interventions and better outcomes for complex medical conditions. Hematopoietic stem cell transplantation (HCT) is a prime example of a complex medical treatment that causes significant symptom burdens for patients. We developed a mHealth app for HCT patients to allow for daily evaluation of patient health and symptoms. We conducted a survey to evaluate interest and usability in a group of HCT survivors and piloted this app with allogeneic HCT patients in a phase 1 clinical trial.Methods: In collaboration with Sicklesoft Inc., we developed a mHealth app, Technology Recordings to better Understand BMT (TRU-BMT), to facilitate wellness tracking and symptom reporting. Patients can enter their food intake, exercise, sleep habits, general health, mood, and daily symptoms (Figure 1). The app provided automatic reports to patients with information about trends over time. To gain feedback and gauge interest, we surveyed transplant survivors at the 2017 BMT InfoNet Symposium in Raleigh, North Carolina. Participants explored the app on iPads and then answered a user experience survey developed with the Behavioral Health and Survey Research Core to evaluate both usability as well as perceived helpfulness. To test real-world usability and feasibility of daily data entry, we also enrolled patients actively undergoing allogeneic HCT in a phase 1 trial. Patients were given Apple devices (iPad Mini, iPad Air) containing the TRU-BMT app to use at the start of transplant. Patients were taught how to use the app and received follow up visits to ensure that they were not struggling to enter data and that no technical difficulties were occurring with the devices.Results: A total of 31 surveys were collected at the BMT InfoNet Symposium. The median age was 62 (range 26-76), 55% were male. 76% of respondents thought TRU-BMT was easy to use; 67% felt confident in its use after only a few minutes of testing; and 80% thought most people could learn to use the app quickly. 83% thought daily symptom input would be useful. 76% would use the app at least 4 times per week, with 44% would use it daily. While there was a correlation between how helpful a participant perceived TRU-BMT and the number of days per week they could see themselves using the app, there was no correlation between age and any of the above responses.Nine patients have been enrolled on the phase I study to determine feasibility (Table 1). Four patients used TRU-BMT nearly every day throughout their transplant, one used TRU-BMT 2-3 times per week throughout transplant, and two are ongoing. One patient enrolled but never started using the app due to multiple medical complications surrounding conditioning chemotherapy. One patient used TRU-BMT for three days but then developed a medical complication, felt overwhelmed, and stopped. Patients have self-reported that in addition to filling out the app themselves, their caregivers also assisted in this process.Discussion: To our knowledge, TRU-BMT is the first mobile health app that specifically addresses symptom reporting and general wellness in the HCT patient population. Patients think such an app is useful, and they will use it daily for up to 90 days during transplant. One of the main concerns in using mHealth apps is making it accessible to patients of all ages. However, according to feedback from survey participants as well as patients using the app, age does not seem to impact a patient's desire or ability to use the app or wearable device. The biggest barrier to consistent use appears to be the health of the patient, as those who had the lowest number of entries or shortest duration of use had complicated transplants, during which symptom management and rest took precedence over data entry. We aim to continue evaluating this app in the setting of long-term follow up and surveillance of symptoms and early detection of complications such as chronic graft-versus-host disease. Given that our most significant challenge in adherence was the medical status of the patient, we predict that patients who have been successfully discharged from transplant will have an easier time complying. Our goal is to facilitate communication between the patient and the healthcare team, permitting closer follow up leading to improved outcomes. [Display omitted] DisclosuresSung:Merck: Research Funding; Novartis: Research Funding; Cellective: Research Funding. Shah:Alexion: Other: Speaker; Novartis: Other: Speaker.

Cardiorespiratory fitness and physical performance after childhood hematopoietic stem cell transplantation: a systematic review and meta-analysis.

The effects of childhood hematopoietic stem cell transplantation (HSCT) on key organs can impair cardiorespiratory fitness, muscle strength, and physical performance. We aimed to provide an overview of childhood HSCT survivors' status on these parameters compared with healthy controls and discuss current insights into clinical risk factors. We performed a systematic search in six scientific databases, including studies published before April 2019 and performed a meta-analysison cardiorespiratory fitness. Muscle strength and physical performance status were presented narratively. We included ten studies embodying 517 childhood HSCT survivors (mean 17.8 years at follow-up). The meta-analysis (n = 4 studies) showed that childhood HSCT survivors have lower cardiorespiratory fitness compared with healthy controls (Standard mean difference (SMD) -1.32 [95% CI -1-58 to -1.07]; I2 2%, p < 0.00001). Collectively, the studies indicated that childhood HSCT survivors have lower muscle strength (n = 4 studies) and physical performance (n = 3 studies) compared with healthy controls. Childhood HSCT survivors have impaired cardiorespiratory fitness years after ended treatment. Muscle strength and physical performance seem to be impaired, although these measures are insufficiently investigated. Associations between HSCT-specific clinical risk factors and cardiorespiratory fitness, muscle strength, and physical performance are required.

Chronic kidney disease ten years after pediatric allogeneic hematopoietic stem cell transplantation

Chronic kidney disease (CKD) is an important sequela of hematopoietic stem cell transplantation (HSCT), but data regarding CKD after pediatric HSCT are limited. In this single center cohort study, we evaluated the estimated glomerular filtration rate (eGFR) dynamics, proteinuria and hypertension in the first decade after HSCT and assessed risk factors for CKD in 216 pediatric HSCT survivors, transplanted 2002-2012. The eGFR decreased from a median of 148 to 116 ml/min/1.73 m2 between pre-HSCT to ten years post-HSCT. CKD (KDIGO stages G2 or A2 or more; eGFR under 90 ml/min/1.73m2 and/or albuminuria) occurred in 17% of patients. In multivariate analysis, severe prolonged stage 2 or more acute kidney injury (AKI), with an eGFR under 60ml/min/1.73m2 and duration of 28 days or more, was the main risk factor for CKD (hazard ratio 9.5, 95% confidence interval 3.4-27). Stage 2 or more AKI with an eGFR of 60ml/min/1.73m2 or more and KDIGO stage 2 or more AKI with eGFR under 60ml/min/1.73m2 but recovery within 28 days were not associated with CKD. Furthermore, hematological malignancy as HSCT indication was an independent risk factor for CKD. One third of patients had both CKD criteria, one third had isolated eGFR reduction and one third only had albuminuria. Hypertension occurred in 27% of patients with CKD compared to 4.4% of patients without. Tubular proteinuria was present in 7% of a subgroup of 71 patients with available β2-microglobulinuria. Thus, a significant proportion of pediatric HSCT recipients developed CKD within ten years. Our data stress the importance of structural long-term monitoring of eGFR, urine and blood pressure after HSCT to identify patients with incipient CKD who can benefit from nephroprotective interventions.

MO452CHRONIC KIDNEY DISEASE TEN YEARS AFTER PEDIATRIC ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Abstract Background and Aims Chronic kidney disease (CKD) is an important sequela of hematopoietic stem cell transplantation (HSCT), but data regarding CKD after pediatric HSCT are limited. Method In this single center cohort study, we evaluated eGFR dynamics, proteinuria and hypertension in the first decade after HSCT and assessed risk factors for chronic kidney disease in 216 pediatric long term HSCT survivors, transplanted between 2002 and 2012. Results The eGFR decreased from median 148 to 116 ml/min/1.73m2 between pre-HSCT and ten years after HSCT. CKD, defined as an eGFR &amp;lt;90 ml/min/1.73m2 and/or proteinuria (KDIGO stage ≥G2 or ≥A2) occurred in 21% of patients. In multivariate analysis, hematological malignancy as HSCT indication (HR 5.5, 95% CI 1.2-25) and cytomegalovirus reactivation (HR 2.4, 95% CI 1.1-5.4) were independent risk factors for CKD. One third of patients with CKD had both an eGFR &amp;lt;90 ml/min/1.73m2 as well as proteinuria, one third had isolated eGFR reduction and one third only had proteinuria. Hypertension was observed in 27% of patients with CKD compared to 4.4% of patients without CKD. Tubular proteinuria was present in 7% of the subgroup of patients (n=71) in which β2-microglobulinuria was measured. Conclusion In conclusion, a significant proportion of pediatric HSCT recipients developed chronic kidney disease within ten years after HSCT. Our data stress the importance of structural long term monitoring of eGFR, urine and blood pressure after HSCT to identify patients with beginning CKD who could benefit most from nephroprotective interventions.

Cardiovascular Issues in Hematopoietic Stem Cell Transplantation (HSCT).

Hematopoietic stem cell transplantation (HSCT) is considered, since 1957, a potentially curative therapeutic option for many hemopathies. Although it is an aggressive procedure, improvements in transplantation techniques and supportive strategies have markedly decreased treatment-related mortality, and the prevalence of HSCT survivors is expected to exceed half a million by 2030. At the same time, there is a growing awareness of the potentially negative effects of HSCT-related therapies on the cardiovascular (CV) system, and HSCT survivors constitute a population at high cardiovascular (CV) risk. Cardio-oncology has been proposed as a new approach to prevent cardiovascular toxicity during and after HSCT. The present article attempts to provide a multidisciplinary and practical approach to the prevention, monitoring, and management of the most common cardiovascular complications in patients undergoing hematopoietic stem cell transplantation.

Evaluation of fatigue and related factors in survivors of pediatric cancer and hematopoietic stem cell transplant.

This study sought to better understand specific factors contributing to fatigue in survivors of pediatric cancer and hematopoietic stem cell transplant (HSCT). As part of a larger study evaluating long-term psychosocial functioning of pediatric cancer survivors, N = 87 participants completed measures assessing fatigue and emotional and behavioral functioning. Chart abstraction was used to catalog diagnosis, treatments received, treatment intensity, and late effects. Results suggest clinically significant fatigue in n = 4 (4.6%) of survivors participating in this study. Fatigue was greater for participants with more recent diagnoses and who were more recently off treatment and was positively associated with parent and self-report of internalizing (emotional) and externalizing (behavioral) symptoms. Participants with more severe late effects suffered greater fatigue; however, fatigue was not associated with treatment intensity or therapy type. Fatigue is an important variable to consider in evaluating the social, emotional, behavioral, and physical well-being of cancer and HSCT survivors. Interventions are needed to address fatigue directly, while also addressing both contributing factors to fatigue and potential negative outcomes that result from fatigue in survivorship.

Gut Microbiota Dysbiosis Associated with Persistent Fatigue in Hematopoietic Cell Transplantation Survivors

Fatigue is one of the most prevalent and distressing complications among hematopoietic stem cell transplantation (HCT) survivors, negatively affecting physical, social, and emotional domains of quality of life. Chronic systemic inflammation has been linked to alterations in nervous system activity and initiation of distressing symptoms, such as fatigue. Damage to gut mucosa due to alteration in gut microbiota (GM) composition and microbial translocation has been shown to increase systemic proinflammatory cytokines. The aim of this study was to evaluate the relationship between fatigue and GM by measuring the differences in GM composition in HCT survivors with and without persistent fatigue. This cross-sectional study included 30 adults who underwent HCT for a hematologic disease and were at least 1 year post-HCT. Patients with chronic graft-versus-host disease were excluded. Fatigue severity was assessed by the Brief Fatigue Inventory (BFI). Based on the BFI score, patients were grouped into 2 categories: 0 to 3 (without fatigue) and ≥4 (with fatigue). The V1 to V3 region of the 16S rRNA gene from fecal specimens was sequenced using the Illumina MiSeq. Sequencing reads were processed, denoised, and replicated, chimeras were filtered, amplicon sequence variants (ASVs) were generated, and taxonomy was assigned using DADA2. Beta diversity analysis through principal coordinate analysis was generated using the Bray-Curtis dissimilarity matrix, and the difference was tested using linear model with generalized least squares in R. An alpha diversity analysis was performed using Chao1. Linear discriminant analysis effect size (LEfSe) was used to find markers that differ between the 2 groups. Based on the BFI results, patients were categorized into 2 cohorts: with fatigue (n=14) and without fatigue (n=16). The 2 cohorts were similar in terms of demographics, disease, and transplant characteristics. Based on the GM analysis, there was a significant difference in GM composition (beta diversity) between the 2 cohorts (P=.001). Alpha diversity (richness) was also significantly lower in survivors with fatigue (P =.002). LEfSe analysis identified 46 discriminative features (P < .05; linear discriminant analysis score >2) whose relative abundance varied significantly among individuals with fatigue and those without fatigue. Ten ASVs were associated with the patients with fatigue, and 36 ASVs were associated with those without fatigue. Several ASVs enriched in survivors with fatigue included organisms such as Klebsiella and Enterococcus, which have been implicated in inflammatory bowel diseases. The ASVs enriched in the cohort without fatigue were members of the Ruminococcaceae family (Oscillospira spp) and the Lachnospiraceae family (Fusicatenibacter and Coprococcus spp), which are known to have the ability to ferment complex plant carbohydrates. These findings show an association between GM composition and fatigue and suggest a microbial contribution to clinically significant fatigue post-HCT, which may guide the development of new approaches to treating fatigue based on manipulation of the GM.

Predictors of quality of life in allogeneic hematopoietic stem cell transplantation survivors

Objectives To establish the demographic, medical, transplant, and lifestyle factors that impact Quality of Life (QoL) in long-term survivors of allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT). Design Cross-sectional study utilizing self-report measures. Sample/Methods In this cross-sectional study of 441 adult survivors of allo-HSCT, participants completed questionnaires assessing QoL, psychological, social, demographic, and clinical variables. Findings Factors associated with improved QoL post-allo-HSCT included time since transplant, female gender, attendance at outpatient appointments, health screening uptake, exercise, and resumption of travel. Factors significantly associated with impaired QoL included chronic morbidities (GVHD), taking psychotropic medication, failure to resume sexual activity (in men), male gender, psychological distress, low income or decline in work status, transition to non-physical work, and necessity for post-allo-HSCT care from various health professionals. Implications for Psychosocial Providers Identification of survivors more likely to experience a reduced QoL following allo-HSCT may enable the targeting of health services to the most vulnerable, and the development of interventions and resources. The data from this study led to the development of HSCT Long-Term Follow Up Clinical Guidelines in New South Wales.

A rationale to prioritise vaccination of HSCT patients against COVID-19

A rationale to prioritise vaccination of HSCT patients against COVID-19

Functional capacity, pulmonary function, and quality of life in hematopoietic stem cell transplantation survivors.

Hematopoietic stem cell transplantation (HSCT) is used as a treatment for several diseases. The objective was to evaluate the functional capacity, pulmonary function, and quality of life (QoL) in HSCT survivors. The patients were submitted to spirometry and six-minute walk test (6MWT) and evaluation of QoL (Functional Assessment of Cancer Therapy Bone Marrow Transplantation-FACT-BMT) and the level of physical activity (Human Activity Profile-HAP) in the post-HSCT outpatient ambulatory. The sample was composed of 103 individuals with a mean age of 42.1 ± 12 and a median HSCT time of 5 (2-11) years. The average distance walked in the 6MWT was 524.7 ± 73.5 m; the FACT-BMT score, 82 ± 8.7 points; FEV1, 76.8 ± 22.6%; and HAP, 71.9 ± 11.2 points. There was a significant difference between debilitated and physically active individuals for the variables: forced expiratory volume in the first second (FEV1) in liters (p = 0.008) and % of predicted (p = 0.017), FEV1/FVC (p = 0.032), distance on the 6MWT (p < 0.001), fatigue after the 6MWT (p < 0.001), and physical well-being (p = 0.005). HSCT survivors have long-term changes in functional capacity, pulmonary function, and QoL. Subjects more active had better results in pulmonary function and functional capacity.