Functional Assessment Of Cancer Therapy-Bone Marrow Transplant Research Articles

Health-related quality of life with gilteritinib vs placebo posttransplant for FLT3-ITD+ acute myeloid leukemia

AbstractThe Blood and Marrow Transplant (BMT) Clinical Trials Network conducted a phase 3 randomized trial comparing gilteritinib with placebo after allogeneic hematopoietic cell transplantation (HCT) for FLT3-ITD+ acute myeloid leukemia (AML). The primary analysis demonstrated no statistically significant difference in relapse-free survival (RFS); however, patients with FLT3-ITD measurable residual disease (MRD) peri-HCT had significantly longer RFS with gilteritinib. This analysis investigates the effect of post-HCT gilteritinib vs placebo on health-related quality of life (HRQOL). HRQOL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (FACT-Leu), and EuroQOL-5 Dimensions (EQ-5D-5L) at post-HCT randomization; day 29; months 3, 6, 12, 18, 24; and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. HRQOL completion rate was acceptable (>70%) across all time points and measures. There were no differences in HRQOL scores at any time point between cohorts. Clinically meaningful and time to improvement in HRQOL were similar in both arms. Despite higher treatment-emergent adverse effects with gilteritinib, response to the question of being “bothered by side effects of treatment” did not differ between groups. Subgroup analysis of MRD-positive and negative patients demonstrated no differences in HRQOL between arms. For patients with FLT3-ITD+ AML undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. This trial was registered at www.ClinicalTrials.gov as #NCT02997202.

Patient-reported physical well-being predicts good long-term survival of hematopoietic stem cell transplantation.

This study aimed to explore the association between patient-reported items at different time points after hematopoietic stem cell transplantation (HSCT) and long-term survival. We conducted a study with 144 allogeneic HSCT patients, following them for 5 years post-transplantation. Data from the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire were collected before transplantation and at 1, 3, 6, 12, 18, 36, and 60 months after transplantation. Demographic characteristics and survival status were also assessed. Among the 144 cases, the 5-year overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease-free (GRFS) rates were 65%, 48%, 17%, and 36% respectively. Health-related quality of life (HRQOL) showed a fluctuating pattern over 5 years. Using a latent class mixed model, patients were classified into two groups based on their physical well-being (PWB) scores during the 60-month follow-up. Class 1 had initially lower PWB scores, which gradually increased over time. In contrast, Class 2 maintained higher PWB scores with slight increases over time. Kaplan-Meier survival analysis revealed that Class 1 had better OS (70.9% vs. 52.9%, p = 0.021), PFS (60.5% vs. 41.2%, p = 0.039), and GRFS (35.1% vs. 29.3%, p = 0.035) compared to Class 2. Patients who had higher initial PWB scores after HSCT demonstrated improved long-term survival outcomes. The PWB score could serve as a valuable predictor for the prognosis of HSCT.

Patient-Reported Outcomes and Mortality in Cutaneous Chronic Graft-vs-Host Disease

Chronic graft-vs-host disease (GVHD) is associated with impaired quality of life and symptom burden. The independent association of skin involvement with patient-reported outcomes (PROs) and their utility as a clinical prognostic marker remain unknown. Identification of patients with cutaneous chronic GVHD and impaired PROs could assist in initial risk stratification and treatment selection. To compare the association of sclerotic and epidermal-type chronic GVHD with longitudinal PROs and to evaluate whether PROs can identify patients with cutaneous chronic GVHD at high risk for death. This multicenter prospective cohort study involved patients from the Chronic GVHD Consortium of 9 US medical centers, enrolled between August 2007 and April 2012, and followed up until December 2020. Participants included adults 18 years and older with a diagnosis of chronic GVHD requiring systemic immunosuppression and with skin involvement during the study period. Patient-reported symptom burden was assessed using the Lee Symptom Scale (LSS) skin subscale with higher scores indicating worse outcomes. Quality of life was measured using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) instrument with lower scores indicating worse outcomes. Nonrelapse mortality, overall survival, and their association with PROs at diagnosis were also assessed. Among 436 patients with cutaneous chronic GVHD (median [IQR] age at transplant, 51 [41.5-56.6] years; 261 [59.9%] male), 229 patients had epidermal-type chronic GVHD (52.5%), followed by 131 with sclerotic chronic GVHD (30.0%), and 76 with combination disease (17.4%). After adjusting for confounders, patients with sclerotic chronic GVHD had mean FACT-BMT scores 6.1 points worse than those with epidermal disease (95% CI, 11.7-0.4; P = .04). Patients with combination disease had mean LSS skin subscale scores 9.0 points worse than those with epidermal disease (95% CI, 4.2-13.8; P < .001). Clinically meaningful differences were defined as at least 7 points lower for FACT-BMT and 11 points higher for LSS skin subscale. At diagnosis, clinically meaningful worsening in FACT-BMT score was associated with an adjusted odds of nonrelapse mortality increased by 9.1% (95% CI, 2.0%-16.7%; P = .01). Similarly, for clinically meaningful worsening in LSS skin subscale score, adjusted odds of nonrelapse mortality increased by 16.4% (95% CI, 5.4%-28.5%; P = .003). These associations held true after adjusting for clinical severity by the National Institutes of Health Skin Score. The results of this cohort study demonstrated that skin chronic GVHD was independently associated with long-term PRO impairment, with sclerotic and combination disease carrying the highest morbidity. The degree of impairment at skin chronic GVHD diagnosis was a prognostic marker for mortality. Therefore, PROs could be useful for risk stratification and treatment selection in clinical practice and clinical trials.

Hematopoietic Stem Cell Transplantation Impact on Patients' Perceived Quality of Life: A Longitudinal Study.

The aim of this paper was to evaluate the quality of life of adult patients with onco-hematological disease treated with hematopoietic stem cell transplantation up to two years post-transplantation. A quantitative, observational, longitudinal, and analytical study was conducted with 121 participants diagnosed with onco-hematological cancer who underwent hematopoietic stem cell transplantation between October 2017 and September 2019, with a 2-year post-transplantation follow-up, of whom only 39 completed the study. The Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire and its subscales, Functional Assessment of Cancer Therapy-General (FACT-BMT) and Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI), developed by the Functional Assessment of Chronic Illness Therapy (FACIT) and validated for Spain, were used to assess quality of life. The average age for hematopoietic stem cell transplantation was 54 years, with a majority of male participants. The evaluation of quality of life showed a decrease at the time of hospital discharge, followed by a progressive improvement up to one year after the transplantation. There was a significant difference in the quality of life questionnaire scores between both sexes during all stages of the research, with higher scores in male participants. The length of hospital stay significantly affected patients' physical and functional well-being, and marital status was related to differences in the perception of quality of life. Despite the initial decrease in quality of life for patients undergoing hematopoietic stem cell transplantation, levels of quality of life similar to baseline are regained one year after the transplantation. Sociodemographic variables are related to how these patients perceive their quality of life. However, further studies with a larger sample size are needed for more precise results.

Title: The Impact of Recent Vaso-Occlusive Crisis on Health-Related Quality of Life in Adults with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is characterized by vaso-occlusive crises (VOCs) and a progressive clinical course, often leading to end organ damage and mortality. Individuals living with SCD with recurrent VOCs experience daily life disruptions due to recurrent pain crises, debilitating chronic pain and fatigue, which substantially impair health-related quality of life (HRQoL). The impact of a recent VOC on HRQoL has not been quantified. We investigated HRQoL impacts in adults with SCD who experienced a recent VOC (&amp;lt; 1 week) in comparison to overall adults with SCD with recurrent VOCs. Methods: A mixed-methods study was conducted to quantify the HRQoL, work impacts, and perceived health inequalities of individuals with SCD with recurrent VOCs. The study consisted of qualitative interviews and an online longitudinal survey administered at 3 timepoints (month 0, 3, and 6) in the US, UK, France, Germany, and Italy. Patient advocacy groups used multi-channel outreach to invite participants, who were required to meet the eligibility criteria and provide consent. Key eligibility criteria included recurrent VOCs defined as ≥ 2 VOCs/year in each of the 2 years prior to enrollment requiring a medical facility interaction and administration of pain medication or red blood cell transfusion. The survey included multiple patient-reported outcome (PROs) measures: the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) inclusive of the FACT-General (FACT-G), EuroQol- 5 Dimension 5-Level (EQ-5D-5L), 11-point pain numerical rating scale (NRS), Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), and the Work Productivity and Activity Impairment (WPAI) questionnaire. In this post-hoc analysis study participants with a current or recent VOC (&amp;lt; 1 week ago) were identified based on ASCQ-Me responses (herein referred to as recent VOC). The HRQoL impact of a recent VOC was assessed by descriptively comparing PRO scores between those with a recent VOC and the overall population of adults with SCD with recurrent VOCs (herein referred to as overall population). Results: The survey was completed by 142 participants with SCD (≥ 18 years) with 139 providing time since last VOC living in the US (n=82) and UK, Germany, France, and Italy (n=57). Fifty-six (40.3%) reported a recent VOC and had a similar mean age (35.7 vs. 35.3 years) and hydroxyurea use in the past month (58.9% vs. 61.9%) compared with the overall population. A higher proportion of those with a recent VOC were unemployed or unable to work due to SCD (76.8% vs. 64.7%). The mean EQ-5D VAS (0-100 scale, 100=best health) among those with a recent VOC was 49.2 (SD: 14.2), which was 16.2% and 38.8% lower relative to the overall study population (58.7 [SD: 19.4]) and the US general population (80.4 [SD: 15.6]), respectively. The overall mean EQ-5D health utility US index score (0.59 [SD: 0.27]) was much lower than the US general population (0.85 [SD: 0.21]) and further reduced among those with a recent VOC by 0.11 (0.48 [SD: 0.25]). The FACT-G total mean score was 53.6 (SD: 14.3) (0-108 scale, 108=best HRQoL) among those with a recent VOC representing a clinically meaningful reduction compared with the overall population (62.5 [SD:18.1]); with all FACT-G domain scores negatively impacted by a recent VOC. Based on the WPAI, those employed with a recent VOC (n=15) reported a mean of 35.4% (SD: 35.8%) absenteeism and 62.5% (SD: 21.8%) presenteeism, which were higher than the overall study population (24.7% [SD: 27.1%] and 42.0% [SD: 27.8%)], respectively). In the past 12 months, those with a recent VOC had a greater mean number of emergency room visits (9.6 [SD: 12.6] vs 6.2 [SD: 8.8]), hospitalizations with overnight stays (6.0 [SD: 5.7] vs. 4.0 [SD: 4.5]), and days overnight in the hospital (21.8 days [SD: 32.9] vs. 14.7 [SD: 24.7]) compared to the overall population. Conclusions: Despite current treatments, nearly 40% of adults with SCD in the surveyed population experienced a recent VOC (&amp;lt; 1 week), which has significant negative impacts on HRQoL and functional status, including the ability to work. These results demonstrate the substantial humanistic burden of those living with SCD with recurrent VOCs and the additional impairment of a recent VOC. Novel treatments that reduce or eliminate VOCs may provide an opportunity to improve health inequalities, HRQoL, and address unmet needs in this patient population.

Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis

AbstractPatient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.

Randomized Controlled Trial of Isha Kriya versus Observation to Improve Quality of Life in Hematopoietic Cell Transplantation Recipients

Hematopoietic cell transplantation (HCT) impacts its recipients' quality of life (QoL). Few mindfulness-based interventions (MBI) in HCT recipients have shown feasibility, but heterogeneous practices and outcome measures have questioned the real benefit. We hypothesize that a self-guided meditation as a mobile app will improve QoL in the acute HCT setting. This single-center, open-label, randomized controlled trial was conducted in 2021-2022. The study was cleared by Institutional Ethics Committee and registered at the Clinical Trial Registry of India. Recipients were included after obtaining written informed consent. Recipients without access to smartphones or regular practitioners of yoga, meditation, or other mind-body practice were excluded. Autologous + allogeneic HCT recipients of age ≥ 18 years were included in the study. Recipients were randomized to the control arm or Isha kriya arm in a 1:1 ratio stratified by type of transplant. Patients in the Isha kriya arm were recommended to perform the kriya twice daily from pre-HCT to day+30 post-HCT. Isha Kriya is 12-minute guided meditation based on the principles of yoga, focussing on breath, awareness, and thought. The primary endpoint was the QoL summary scores assessed by the Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) and the Patient-Reported Outcomes Measurement Information System–Global Health (PROMIS-GH) questionnaires. The secondary endpoints were the difference in QoL domain scores. The validated questionnaires were self-administered before the intervention, day +30, and day +100 after HCT. The analysis of endpoints was done on an intention-to-treat basis. Domain and summary scores were calculated for each instrument as recommended by the developers. A p-value <0.05 was used for statistical significance, and cohen's d effect size determined clinical significance. A total of 72 HCT recipients were randomized to the Isha kriya and the control arm. Patients in both arms were matched for age, gender, diagnosis, and type of HCT. Both arms had no difference in the pre-HCT QoL domain, summary, and global scores. Post-HCT at day+30, there was no difference in the mean FACT-BMT total scores (112.9 ± 16.8 vs.101.2 ± 13.9, p = 0.2) and the mean global health scores (Global mental health 45.1 ± 8.6 vs. 42.5 ± 7.2, p = 0.5, global physical health 44.1 ± 6.3 vs. 44.1 ± 8.3, p = 0.4) in the two groups. There was similarly no difference in the physical, social, emotional, and functional domain scores. However, the mean BMT-subscale scores, which addresses BMT-specific quality-of-life concerns, were statistically and clinically significantly higher in the Isha kriya arm than the control arm (27.9 ± 5.1 vs. 24.4 ± 9.2, p = 0.03, Cohen's d 0.5, medium effect size). This effect was transient as the day+100 scores showed no difference (28.3 ± 5.9 vs. 26.2 ± 9.4, p = 0.3). Isha kriya did not improve the FACT-BMT total and global health scores in the acute HCT setting. However, practicing Isha kriya for a month did show a transient improvement in the FACT-BMT subscale scores on day +30 but not on day +100 post-HCT.

Evaluation of the quality of life of adult patients admitted to the bone marrow transplantation unit.

The complexity of treatment and extended therapy duration associated with bone marrow transplantation directly affect the psychological well-being of the patients, create anxiety, and reduce their quality of life. The aim of our study was to evaluate the quality of life of patients admitted to the bone marrow transplantation unit. This prospective and descriptive study was conducted between January and June 2021 in an adult BMT unit in Turkey. The sociodemographic characteristics of the patients were recorded. The patient's quality of life was measured twice using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) scale at the beginning of the study and 30 days later. SPSS 15 was used for the analysis. A total of 40 patients were included in the study. The mean age was 46 years. Most of the patients were diagnosed with multiple myeloma and 58% had at least one comorbid disease. Most of the patients (78%) were receiving myeloablative therapy. High dose melphalan regimen was the most commonly applied regimen (25%). Thrombocytopenia was the most common side effect (14%). Although there was no change in the quality of life, it was found that the social/family well-being scores increased (p < 0.05). In our study, it was observed that the number of comorbid diseases was higher in patients with bone marrow transplantation. The incidence of side effects may be high in these patients. We believe that clinical pharmacists have an important role in monitoring adverse effects and improving the quality of life in bone marrow transplantation units.

Fatigue as Mediator Factor in PTSD-Symptoms after Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a valid treatment for hematological oncological or metabolic diseases. Despite its therapeutic efficacy, it is an aggressive treatment that impacts negatively on quality of life (QoL) and may result in Post-Traumatic Stress Disorder (PTSD) symptoms. The aim of this study is to explore rates and risk factors for PTSD symptoms, and fatigue in post-HSCT patients with hematological malignancies. A total of 123 patients after HSCT were evaluated for PTSD symptoms, QoL and fatigue. PTSD symptoms were assessed with the Impact of Event Scale- Revised (IES-R), QoL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) and fatigue symptoms were assessed with Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). A total of 58.54% of the sample developed PTSD symptoms after transplant. Patients with PTSD symptoms reported significantly lower QoL total scores and significantly higher fatigue than those without PTSD symptoms (p < 0.001). The SEM analysis showed that worse QoL and fatigue affected PTSD symptomatology along different pathways. Fatigue was found as a major influencing factor of PTSD symptoms directly (β = 0.31 **), while QoL only through the mediation of fatigue at a lesser extent. (β = 0.33 *). Our findings indicate that QoL is a concurrent causative factor to the development of PTSD symptomatology through the mediating role of fatigue. Innovative interventions before transplantation to prevent PTSD symptoms should be investigated to improve survival and QoL in patients.

Frailty in Patients with Chronic Graft-versus-Host Disease

Frailty is an increasingly recognized clinical diagnosis associated with high risk of disability and mortality. Frailty in patients after hematopoietic cell transplantation (HCT) is associated with increased nonrelapse mortality (NRM) and decreased overall survival (OS). Frailty has not been studied extensively in patients with chronic graft-versus-host disease (cGVHD). The objectives of the present study were to assess the prevalence and clinical correlates of frailty and the association of frailty with NRM and OS in patients enrolled in the Chronic GVHD Consortium. Patients were characterized as frail if they met the Fried definition of ≥3 of the following criteria at enrollment: unintentional weight loss, exhaustion, slow walking speed, low physical activity, and weakness. Frailty was assessed retrospectively using surrogate measures for the 5 domains of frailty. Frailty, cGVHD organ scores, and patient-reported outcomes were measured at the time of enrollment. The study included 399 patients from 9 centers in the United States, with 32% characterized as frail and 68% as not frail. The median duration of follow-up from enrollment was 9 years (interquartile range, 7 to 11 years). Frail patients were more likely to be older (P=.004), to have a lower Karnofsky Performance Status (P < .001), to have severe cGVHD (P < .001), and to have gastrointestinal (P < .001), liver (P=.04), or lung cGVHD (P=.002). In a multivariable analysis, older age, increased cGVHD global severity, and thrombocytopenia were statistically significantly associated with frailty when cGVHD organ involvement was excluded. A separate analysis excluding cGVHD severity and including organ involvement showed that lung and liver cGVHD and older age were associated with frailty. Neither corticosteroid use at the time of enrollment nor the maximum recorded dose of corticosteroids before enrollment was associated with frailty. Frail patients had higher NRM than nonfrail patients (P < .001), with a 10-year cumulative incidence of 41% (95% confidence interval [CI], 32% to 49%) versus 22% (95% CI, 17% to 28%). Reciprocally, frailty also was associated with a significantly lower OS (P < .001), with a 10-year OS of 43% (95% CI, 35% to 53%) in frail patients versus 63% (95% CI, 57% to 69%) in nonfrail patients. In multivariable analysis that included the individual domains of frailty, weakness, low physical activity, and slow walking speed were associated with survival. Frail patients also had worse scores on various measures of patient-reported outcomes, including the Short Form (SF)-36, the Lee Symptom Scale, and the trial outcome of the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) index score. Frail patients with cGVHD have significantly worse outcomes than nonfrail patients. Such clinical features as older age and lung and liver cGVHD are associated with frailty. Earlier clinical recognition of frailty in patients with cGVHD may prompt interventions to counteract frailty that could be beneficial for this population.

Health-Related Quality of Life and Disease Impacts in Adults with Transfusion-Dependent β-Thalassemia: Preliminary Results from the Global Longitudinal Survey

Introduction: Transfusion-dependent β-thalassemia (TDT) is a chronic inherited blood disorder requiring frequent red blood cell transfusions and daily iron chelation therapy. Health-related quality of life (HRQoL) of individuals with TDT is impacted by a multitude of factors, including iron overload-related morbidity, substantial time required to manage TDT, and work and activity impairments. Nonetheless, the HRQoL impact of TDT is not well quantified. Here, we report the preliminary findings from a prospective longitudinal study evaluating the HRQoL and work productivity impacts among adult participants with TDT. Methods: A mixed-methods study was conducted to quantify the symptoms, HRQoL, and work and education impacts of adults with TDT. The study consisted of qualitative interviews and an online longitudinal survey administered at 3 timepoints (time 0, 3 months, 6 months) in the US, the UK, France, Germany, and Italy. The survey aimed to quantify the HRQoL impacts using multiple patient-reported outcomes measures (PROMs): the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), composed of the Functional Assessment of Cancer Therapy-General (FACT-G) and a BMT subscale (BMTS); EuroQol 5-Dimension 5-Level (EQ-5D-5L); Transfusion-dependent Quality of Life (TranQoL); and Work Productivity and Activity Impairment (WPAI) questionnaire. Symptoms, comorbidities, treatment experiences, out-of-pocket costs, and time spent managing TDT were also collected and evaluated. Survey invitations were sent to patient communities via patient advocacy groups. Participants were required to meet the eligibility criteria and provide consent. Eligibility criteria included receiving ≥8 blood transfusions/year in each of the 2 years prior to enrollment. Descriptive analyses were conducted for participant characteristics and PROMs based on survey findings at time 0. Results: The survey was completed by 155 adult participants with TDT (aged ≥18 years) living in the US (n=83) and the UK, Germany, France, and Italy (n=72). Overall, 65.8% (n=102) were female, the mean age was 38.5 years (standard deviation [SD]: 10.8 years), and 32.9% (n=51) had full-time employment (32 hours/week). Participants reported a mean of 18.7 (SD: 8.2) transfusions in the previous 12 months. The mean FACT-G score was 70.1 (SD: 19.0) (0-108 scale; 108=best HRQoL), which is lower than the US general population mean of 80.1 (SD: 18.1). The largest HRQoL impact was observed on the emotional well-being domain of the FACT-G (-21.9% relative change) (mean: 14.7 [SD: 4.4] compared with the US general population (mean: 9.9 [SD: 4.8]) (0-24 scale; 24=best HRQoL). Participants reported a mean EQ-5D-5L visual analog scale score of 67.1 (SD: 20.4), with 73.2% reporting pain/discomfort, 60.8% anxiety/depression, 46.4% mobility impairment, and 24.8% self-care impairment. The mean TranQoL total score was 53.9 (SD: 18.5) (100-point scale; 100=best HRQoL). Forty percent of the participants felt that TDT limited their career opportunities "often” or "always.” Participants reported spending substantial time managing their condition in the last month, with 62.4% spending >6 hours at medical appointments and 36.1% needing >6 hours of care from family members/caregivers to manage their condition. Among those employed (n=84), 34.4% (SD: 30.9%) reported work impairment (presenteeism), 19.5% (SD: 25.5%) absenteeism, and 41.7% (SD: 32.4%) work productivity loss on the WPAI. Among all respondents (n=151), the mean activity impairment was 44.2% (SD: 31.0%). Results were consistent in a subset of 18-to-35-year-old participants. Conclusions: Adults with TDT currently receiving treatment experience significant HRQoL impacts and impaired work productivity and spend considerable time managing their disease, indicating significant humanistic burden and unmet needs in this patient population.

Health-Related Quality of Life, Disease Impacts, and Health Equity Concerns in Adults with Sickle Cell Disease with Recurrent Vaso-Occlusive Crises: Preliminary Results from a Global Longitudinal Survey

Introduction: Sickle cell disease (SCD) is characterized by vaso-occlusive crises (VOCs) and a progressive clinical course, often leading to end-organ damage and accelerated mortality. Individuals with SCD with recurrent VOCs experience disruptions to daily life due to recurrent pain crises and debilitating chronic pain and fatigue, which affect their ability to work and substantially impair their health-related quality of life (HRQoL). Nonetheless, HRQoL and disease impacts in this population are not well quantified. Here, we report preliminary findings from a prospective longitudinal study evaluating the HRQoL, work productivity impacts, and health equity concerns among adult participants with SCD with recurrent VOCs. Methods: A mixed-methods study was conducted to quantify the symptoms, HRQoL, and work impacts of adults with SCD with recurrent VOCs. The study consisted of qualitative interviews and an online longitudinal survey administered at 3 timepoints (time 0, 3 months, and 6 months) in the US, the UK, France, Germany, and Italy. The survey included multiple patient-reported outcomes measures (PROMs): the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), composed of the Functional Assessment of Cancer Therapy-General (FACT-G) and a BMT subscale (BMTS); EuroQol 5-Dimension 5-Level (EQ-5D-5L); 11-point pain Numerical Rating Scale (NRS); Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me); and Work Productivity and Activity Impairment (WPAI) questionnaire. Symptoms, comorbidities, treatment experiences, out-of-pocket costs, time spent managing SCD, and participants' health equity concerns were also collected and evaluated. Survey invitations were sent to patient communities via patient advocacy groups. Participants were required to meet the eligibility criteria and provide consent. Eligibility criteria included experiencing ≥2 VOCs/year, in each of the 2 years before study enrollment, that required interaction with a healthcare provider and administration of pain medication or a red blood cell transfusion. Descriptive analyses were conducted for participant characteristics and PROMs based on survey findings at time 0. Data are reported as mean (standard deviation [SD]), unless noted. Results: The survey was completed by 142 participants with SCD (aged ≥18 years) living in the US (n=85) and the UK, Germany, France, and Italy (n=57) at time 0. Overall, 71.8% were female (n=102), the mean age was 35.5 years (10.4), and 15.5% (n=22) had full-time employment (≥32 hours/week). In the prior 12 months, participants reported a mean of 5.9 (4.8) VOCs that required interaction with a healthcare provider and pain medication and spent a mean of 14.6 (24.7) days in the hospital. In the past month, 62.0% (n=88) were taking hydroxyurea to manage their condition. The mean FACT-G total score was 62.2 (18.5) (0-108 scale; 108=best HRQoL), which is lower than in the US general population (80.1 [18.1]). The largest impacts were observed on the physical (-23.9% relative difference) and emotional well-being domains (-16.3% relative difference) vs the US general population. Participants reported a mean EQ-5D-5L visual analog scale score of 58.7 (19.4), with 89.9% reporting pain/discomfort, 74.1% anxiety/depression, 71.2% mobility impairment, and 46.8% self-care impairment. Significant HRQoL impairments were also observed on the ASCQ-Me vs the SCD reference population, with the largest differences observed on the pain (41.5 [9.0]), stiffness (41.1 [8.2]), and emotional (43.5 [7.6]) impact domains. Among those employed (n=47), 42.0% (27.8%) reported work impairment (presenteeism), 24.7% (27.1%) absenteeism, and 53.4% (27.5%) work productivity loss on the WPAI. Among all respondents (n=137), the mean activity impairment was 52.6% (26.0%). On healthcare equity concerns, 68.3% (n=97) felt that they had been treated unfairly while seeking care, with most attributing the unfair treatment to their race/ethnic background (67.0%) and/or requesting more pain medicine (64.9%). Results were consistent in a subset of 18-to-35-year-old participants. Conclusions: Adults with SCD with recurrent VOCs currently receiving treatment experience significant HRQoL impact, impaired work productivity, and health equity concerns, indicating substantial humanistic burden and unmet needs in this patient population.

Association between Patient-Reported Social Determinant of Health Outcomes and a Social Genomics Profile in Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis

Introduction Patient-reported outcomes (PROs) capture the subjective experience of a patient's social and environmental context, providing a firsthand account of this and other social determinants of health (SDOH). An individual's socioenvironmental context is linked to a wide array of health outcomes, including for patients undergoing hematopoietic cell transplantation (HCT) [1, 2]. Social genomics, the study of socioenvironmental effects on human gene expression, offers a framework for understanding these complex biobehavioral relationships [3]. The conserved transcriptional response to adversity (CTRA) is a genomic biomarker characterized by increased expression of pro-inflammatory genes and decreased innate anti-viral gene expression [4]. The CTRA profile has been associated with psychosocial adversity and is predictive of clinical outcomes in HCT, and thus may be a means to map the biologic sequelae of social hardship [2, 4]. The objective of this study was to examine the association of pre-transplant CTRA profile with psychosocial PROs in allogeneic HCT recipients. Methods A cross-sectional analysis of data from a subset of participants enrolled on a prior CIBMTR study testing the feasibility of centralized collection of PROs in allogeneic HCT [5] was completed. For the present analysis, eligible patients from this larger cohort were those aged >18 years with baseline (pre-HCT) PRO measures and available pre-transplant banked biospecimens. PROs included the 36-Item Short Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). Descriptive analyses of patient-, disease-, and transplant-related characteristics were prepared. CTRA was derived from banked whole blood specimens using RNA sequencing. Transcript-per-million values of the 47 indicator genes were log2 transformed and analyzed using mixed effects linear regression models testing relative average gene expression levels to standardized PRO score controlling for age, sex, race, malignant versus non-malignant disease, and performance status. Results A total of n=140 patients representing 8 transplant centers in the United States were included. Patient characteristics are depicted in Table 1. The median age was 55 years (range 18-75y), 44% were female, and 90% identified as White. A majority (96%) of patients had a hematologic malignancy diagnosis, with acute myelogenous leukemia (AML) being most common (35%). There were statistically significant associations between lower CTRA gene expression and higher FACT-BMT total scores (β-coefficient -0.041 difference in log2 CTRA RNA abundance/SD PRO score, p-value=0.003) social well-being (β-coefficient -0.058 difference in log2 CTRA RNA abundance/SD PRO score, p-value=0.0001), physical well-being, (β-coefficient -0.031 difference in log2 CTRA RNA abundance/SD PRO score, p-value=0.031) and FACT-G scores (β-coefficient -0.042 difference in log2 CTRA RNA abundance/SD PRO score, p-value=0.003) as depicted in Figure 1. This corresponds to a 10.7%, 14.8%, 8.2%, and 11.1% difference, respectively, in CTRA gene expression per 4-SD range of variation in each PRO. Conclusions Patient reports of socioenvironmental experience were associated with the CTRA immunoregulatory pattern in adult allogeneic HCT recipients, with social well-being emerging as the most significant domain. This finding is consistent with prior literature and supports the importance of social well-being and community context in the setting of allogeneic HCT. Heightened CTRA expression could provide a potential molecular mechanism for social gradients in HCT outcomes, although this was not experimentally tested in this study. Further research and intervention that targets this pathway could support optimal multidimensional outcomes in this high-risk population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Health-Related Quality of Life Following Allogeneic Hematopoietic Cell Transplantation with Omidubicel versus Umbilical Cord Blood

Omidubicel is an advanced cell therapy derived from umbilical cord blood (UCB) for use in allogeneic hematopoietic cell transplantation (HCT). A recent randomized phase 3 clinical trial demonstrated faster engraftment, shorter length of hospital stays, and lower rates of infection with omidubicel compared with standard UCB transplantation in patients with high-risk hematologic malignancies. Despite the proven clinical benefits of omidubicel, its impact on health-related quality of life (HRQL) from the patient's perspective has not been described. This study analyzed patient-reported HRQL measures collected prospectively in the randomized phase 3 trial comparing omidubicel to standard UCB transplantation. A total of 108 patients at 33 international stem cell transplantation centers underwent myeloablative allogeneic HCT with either omidubicel or standard UCB. Patients completed serial HRQL questionnaires at screening and on days 42, 100, 180, and 365 post-transplantation. The HRQL surveys included the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), a 50-item cancer-specific questionnaire assessing physical, functional, emotional, social/family, and HCT-specific well-being, and the EuroQol 5-Dimension 3-Level, a 5-item generic HRQL survey. A mixed model with repeated measures was used to compare changes in HRQL from baseline in the 2 treatment arms. The average change in HRQL scores over time was compared by estimating the difference in the area under the curve (AUC) in each treatment group. Seventy-five patients (omidubicel arm, n=37; standard UCB arm, n=38) who completed the FACT-BMT at baseline and on 1 or more follow-up visits were included in this study. Baseline characteristics were similar in the 2 treatment arms. Over the first year post-transplantation, the AUCs of mean changes in physical, functional, and total FACT-BMT scores indicated significantly better HRQL with omidubicel (P < .05), with mean differences across time points ranging from 1.4 to 3.1 points, 1.6 to 3.2 points, and 7.2 to 11.0 points, respectively. The minimal clinically important difference was exceeded at 1 or more time points for each of these measures. The HRQL improvements with omidubicel were observed as early as 42 days post-transplantation and persisted at 1 year, indicating the potential long-term benefits of omidubicel on HRQL. Across all patients, adverse clinical outcomes, such as grade 3 viral infections and lower rates of neutrophil engraftment, were associated with worse HRQL scores. The observed improvements in HRQL measures may reflect the known clinical benefits of omidubicel. Compared with standard UCB, allogeneic HCT with omidubicel resulted in significant and clinically meaningful improvements in patient-reported HRQL measures.

Karnofsky performance status and visual analogue scale scores are simple indicators for quality of life in long-term AYA survivors who received allogeneic hematopoietic stem cells transplantation in childhood

The purpose of this study was to investigate Karnofsky performance status (KPS) scores and visual analogue scale (VAS) scores to explain which domains in the standardized self-reported quality of life (QOL) are instrumental for long-term hematopoietic stem cell transplantation (HSCT) survivors. We conducted a nationwide cross-sectional questionnaire study on 221 survivors with allogeneic-HSCT in 28 pediatric centers. Patient-reported QOL was assessed at a single time point using the 36-item Short-Form Survey (SF-36), the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and VAS scores. KPS scores were significantly correlated with both physical and role component summary scores of the SF-36, while the VAS provided by the patient (VASpt) was significantly correlated with the mental component summary score of the SF-36 and many subscales of the FACT-BMT. The VAS provided by the participants' attending physician (VASdoc) was correlated well with KPS scores. A VASpt score more than 40% lower than KPS scores suggested mental health problems. In conclusion, KPS scores might be considered as an indicator for physical and role/social components and VASpt score as an indicator for mental components and HSCT-specific QOL.

Patterns and Predictors of Functional Decline after Allogeneic Hematopoietic Cell Transplantation in Older Adults

As allogeneic hematopoietic cell transplantation (alloHCT) is increasingly offered to older adults, geriatric assessment (GA) has been identified as a useful tool for predicting outcomes, particularly functional status. However, very few studies have examined the longitudinal change in GA measures in the post-alloHCT period. The objectives of this study were to describe the longitudinal change in GA and quality of life (QoL) measures after alloHCT and to identify predictors of greater functional decline post-transplantation. In this single-center prospective cohort study, patients age ≥50 years scheduled for alloHCT completed a cancer-specific GA and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) survey at baseline prior to alloHCT and then at 3, 6, and 12 months post-transplantation. Changes in GA and QoL measures at each post-transplantation time point (3, 6, and 12 months) compared to baseline were analyzed using paired t-tests. Exploration of potential predictors of greater post-transplantation functional decline, as measured by instrumental activities of daily living (IADL) and the Medical Outcomes Study Physical Health scale (MOS-PH), were examined using linear regression and the chi-square 2-sample test of proportions. Mean functional status generally exhibited a pattern of decline at 3 to 6 months post-alloHCT, with recovery to near baseline by 12 months. Mean mental health and emotional QoL were lowest at baseline and improved at all post-transplantation time points. Differences in baseline clinical characteristics were not associated with any differences in functional trajectories. Differences in baseline GA measures-patient-rated Karnofsky Performance Status, IADL, MOS-PH, Timed-Up-and-Go, Blessed Orientation-Memory-Concentration test, and Mental Health Inventory 5-also did not predict greater functional decline at 3 months. Patients whose IADL was improved or maintained at 3 months generally maintained their functional status at 6 and 12 months. Similarly, most patients who had an IADL decline at 3 months still had a functional decline at 6 months, although a proportion did have functional recovery by 12 months. Compared with patients who had improved/maintained IADL at 3 months, those with a decline in IADL at 3 months were significantly more likely to have persistent functional decline at 6 months (P < .0001) and 12 months (P=.02). In older alloHCT recipients, mean functional status declines short term after alloHCT with the possibility of recovery by 6 to 12 months, whereas mean mental and emotional health improve post-alloHCT. Functional decline at 3 months post-alloHCT is associated with persistent functional decline at 12 months.

Comparison of Quality of Life and Outcomes between Haploidentical and Matched Related/Unrelated Donor Allogeneic Hematopoietic Cell Transplantation

Haploidentical (haplo) donor grafts are a well-established alternative donor source for allogeneic hematopoietic cell transplantation (HCT); however, data comparing health-realted quality of life (HRQOL) measures between haplo-HCT and HCT using other donor sources are lacking. We hypothesized that post-transplantation HRQOL might not differ between haplo-HCT and HCT with other graft sources. We conducted a single-institution retrospective analysis comparing HRQOL of haplo-HCT with matched-related donor (MRD) HCT and matched unrelated donor (MUD) HCT for hematologic diseases. We included 90 haplo, 102 MRD, and 229 MUD adult first allogeneic HCTs performed between May 2014 and December 2019. HRQOL for haplo-HCT, MRD-HCT, and MUD-HCT were compared separately for myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC). HRQOL was assessed using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale pretransplantation and at days +100 and +180 post-transplantation. MAC haplo-HCT showed no difference in all domains of HRQOL and other transplantation outcomes, including overall survival, compared with MAC MRD/MUD-HCT, except for a higher incidence of non-cytomegalovirus infections (P=.003). RIC haplo-HCT was associated with significantly better emotional well-being (P=.008) and functional well-being (P=.011) compared with MUD-HCT. RIC haplo-HCT was associated with higher rates of non-cytomegalovirus infections (P < .001) and relapse mortality (P=.044) but a lower rate of nonrelapse mortality (P=.008) compared with RIC MUD-HCT. Haplo-HCT had comparable total HRQOL scores and overall survival to MRD/MUD-HCT in both the MAC and RIC cohorts. Interrogation of HRQOL among disease-specific groups may further elucidate the existence of any additional benefits with these different transplantation modalities.

Objective and subjective physical function in allogeneic hematopoietic stem cell transplant recipients.

We conducted a prospective study of adult allogeneic hematopoietic cell transplantation (HCT) recipients to assess pre- and post-HCT physical function. Baseline measurements included a wrist actigraphy, a 6 min walk test (6MWT), an international physical activity questionnaire (IPAQ), and a Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) as well as serial post-HCT assessments of 6MWT, IPAQ, and FACT-BMT. Forty-seven patients were evaluable for functionality assessments, with a median follow-up of 54.5 months for surviving recipients. No patients demonstrated vigorous or very vigorous activity at any time during monitoring by wrist actigraphy; patients spent a median of 6 h daily sedentary. Self-reported activity via the IPAQ showed 36%, 43%, and 21% of subjects reporting light, moderate, and vigorous activity prior to HCT, respectively. Post-HCT 6MWTs on day +30 demonstrated the greatest association with subsequent survival and non-relapse mortality. A decline in 6MWT distance over time also demonstrated worsened overall survival. This study shows the feasibility of fitness assessments and the ability to risk stratify for subsequent mortality, particularly using the 6MWT on the day +30 single time point assessment and change scores from baseline to day +30 post HCT. These pilot findings suggest important targets for future study.

Guided imagery relaxation in quality of life of patients undergoing hematopoietic stem cell transplantation: a quasi-experiment.

Objective:The aim of this study was to evaluate the effects of the relaxation technique with guided imagery by means of virtual reality on health-related quality of life in patients undergoing hematopoietic stem cell transplantation. Methods:A quasi-experiment conducted in a Bone Marrow Transplantation Service of a public hospital in southern Brazil. From October 2019 to October 2020, forty-two adult participants who underwent transplantation were included, 35 in the intervention group and seven in the control group. A guided imagery intervention, with audio guiding the relaxation associated with nature images in 360º, was performed during the hospitalization period. Data were collected on the first day of hospitalization, on the transplantation day, during the neutropenia stage, and at pre-hospital discharge. The Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and Functional Assessment of Cancer Therapy-Neutropenia (FACT-N) were used to assess health-related quality of life, fatigue and neutropenia. Data were analyzed using the Generalized Linear Mixed Model for the evolution of the health-related quality of life assessments over time, considering the groups and stages. Pearson’s correlation coefficient was adopted for the correlation analyses. Results:Allogeneic transplantation was predominant: 28 (80%) in the intervention group and 5 (71.43%) in the control group. There were improvements in the health-related quality of life scores, although not significant. A significant difference was found among the stages (p<0.050) and a significant positive correlation (p<0.000) among the variables on general quality of life, additional concerns, fatigue and neutropenia in all stages. Conclusion:Patients undergoing hematopoietic stem cell transplantation suffer changes in their quality of life. Interventions based on integrative practices emerge as an option to minimize them.

Validity and reliability of the Turkish version of the functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) quality of life questionnaire in patients undergoing bone marrow transplantation.

The Functional Assessment of Cancer Therapy-Bone Marrow Transplant Version 4 (FACT-BMT) is a widely used instrument to assess quality of life in individuals treated with bone marrow transplantation (BMT). Our aim was to determine the reliability and validity of the Turkish version of the FACT-BMT in patients undergoing BMT. Patients between the age of 20 and 65 years and who had undergone BMT at least 3 months before the study were included. Validity was determined using exploratory and confirmatory factor analysis. To determine convergent validity, the European Cancer Research and Treatment Organization Quality of Life Questionnaire-Cancer30 (EORTC QLQ-C30), the Brief Fatigue Inventory (BFI), and the Eastern Cooperative Oncology Group (ECOG) performance score were used. Cronbach's alpha, intra-class correlation coefficient (ICC), and item-total correlation (ITC) values were calculated to assess the reliability of the FACT-BMT. Totally, 114 patients (F/M: 47/67) treated with BMT (mean age: 49.50 ± 12.50 years) were included. Confirmatory and exploratory factor analysis revealed that the FACT-BMT and the Bone Marrow Transplantation Subscale (BMTS) had sufficient fit. The FACT-BMT was moderately to strongly correlated with the EORTC QLQ-C30, the BFI, and the ECOG performance score (p < 0.001). Cronbach's alpha and ICC values of the FACT-BMT were acceptable (0.925 and 0.956, respectively). The ITC values of each item of the FACT-BMT were also acceptable (ranged from 0.296 to 0.737). Patients undergoing autologous BMT had a significantly higher BMTS score than those undergoing allogeneic BMT (p < 0.05). The Turkish version of the FACT-BMT is valid, reliable, and sensitive to changes in quality of life in patients undergoing BMT.