Survivors Of Allogeneic Stem Cell Transplantation Research Articles

Vascular Aging Is Accelerated in Hematological Cancer Survivors Who Undergo Allogeneic Stem Cell Transplant.

Survivors of allogeneic stem cell transplant (SCT) receive intensive cancer treatments that are associated with cardiovascular dysfunction. Markers of vascular age can indicate early signs of adverse (cardio)vascular changes; however, the impact of SCT on these makers is unknown. We aimed to determine the short (3 months) and longer-term (≥2 years) effect of SCT on markers of vascular age in hematologic cancer survivors compared with an age-matched noncancer control group. The short-term effects of SCT, markers of vascular age (aortic compliance, arterial elastance, and ventricular-vascular coupling) were assessed via cardiac magnetic resonance imaging (cardiac and aortic volumes) before and ≈3 months post-SCT in 13 short-term survivors and compared with 11 controls. The longer-term impact was assessed by comparing 14 long-term survivors (6.5 [2-20] years post-SCT) to the short-term survivors (post-SCT) and controls (n=16). The groups were similar for age and body mass index. In the short-term survivors, no significant group-by-time interactions were observed for any markers of vascular aging from pretransplant to posttransplant (net difference for change in compliance between groups -0.07 [95% CI, -1.49 to 1.35]). For the time-course analysis, aortic compliance was significantly lower in both SCT groups (overall P=0.007) compared with controls, whereas ventricular-vascular coupling was higher in both survivor groups as was arterial elastance in long-term SCT survivors (ie, worse; P<0.01 for all). This study provides evidence of an accelerated vascular aging phenotype in allogeneic SCT survivors and provides insight into the increased burden of cardiovascular disease among hematologic cancer survivors.

Reduced cardiovascular reserve capacity in long-term allogeneic stem cell transplant survivors

Premature cardiovascular mortality is increased in long-term allogeneic stem cell transplant (allo-SCT) survivors, but little information exists regarding subclinical cardiovascular dysfunction in this population. We compared peak oxygen uptake ({{dot{mathrm V}}}O2peak), a prognostic cardiovascular marker, and its determinants between long-term allo-SCT survivors and non-cancer controls. Fourteen allo-SCT survivors (mean ± SD, 44 ± 15 years, 50% male, median time since allo-SCT: 6.5 years [range 2–20]) and 14 age- and sex-matched controls (46 ± 13 years, 50% male) underwent cardiopulmonary exercise testing to quantify {{dot{mathrm V}}}O2peak. Resting echocardiography (left-ventricular ejection fraction and strain), exercise cardiac MRI (peak cardiac and stroke volume index [CIpeak, SVIpeak]), biochemistry (hemoglobin, troponin-I, B-natriuretic peptide), dual-energy x-ray absorptiometry (lean [LM] and fat [FM] mass, percent body fat [%BF]) and Fick-principal calculation (arteriovenous oxygen difference) were also performed. Survivors exhibited impaired {{dot{mathrm V}}}O2peak as compared with controls (25.9 ± 5.1 vs. 33.7 ± 6.5 ml kg−1 min−1, p = 0.002), which coincided with reduced CIpeak (6.6 ± 0.8 vs. 8.6 ± 1.9 L min−1 m−2; p = 0.001) secondary to reduced SVIpeak (48 ± 4 vs. 61 ± 8 ml m−2; p < 0.001) rather than chronotropic impairment, and higher %BF (difference, 7.9%, p = 0.007) due to greater FM (5.8 kg; p = 0.069) and lower LM (4.3 kg, p = 0.25). All other measures were similar between groups. Despite comparable resting cardiac function and biomarker profiles, survivors exhibited reduced {{dot{mathrm V}}}O2peak and exercise cardiac function and increased %BF relative to controls. These results highlight potential therapeutic avenues and the utility of exercise-based cardiovascular assessment in unmasking cardiovascular dysfunction in allo-SCT survivors.

Late cognitive outcomes among allogeneic stem cell transplant survivors: follow-up data from a 6-year longitudinal study

Survivors of allogeneic hematopoietic stem cell transplantation (alloHCT) may experience cognitive impairment over time post-treatment, but early identification of these individuals is limited. We previously reported a prospective evaluation of cognitive functioning over the first 6 months of alloHCT. Here, we report an extension of this study, with specific aims to (1) evaluate the trajectory of cognitive outcomes over the first 6 years post-alloHCT, and (2) determine the extent to which late cognitive impairment is predicted by earlier impairment. Participants completed objective and subjective cognitive measures before alloHCT, and at 100 days, 6 months, and 6 years post-alloHCT. Outcome trajectories were determined using linear mixed effects models. Relationships between early and late cognitive impairment were assessed using logistic regression and receiver operator curves. This analysis is based on longitudinal data from 59 participants, of whom 20 provided data at 6-year follow-up. Longitudinal models revealed an overall stability of cognitive outcomes over time, except for psychomotor efficiency/processing speed performance, which significantly improved (p = .049). However, poor learning/memory and cognitive complaints were persistently observed. At 6 years, 40% of relapse-free survivors met the impairment criteria. Impairment at 100 days was associated with impairment 6 years (OR = 20.00, p = .028) and demonstrated good accuracy in classifying those who were impaired and not impaired at 6 years (AUC = .79; 95% CI = .56-1.00). Poor cognitive outcomes among long-term alloHCT survivors are associated with cognitive functioning during the early post-treatment period. Early identification of survivors likely to experience poor cognitive outcomes may be possible, enabling timely intervention to mitigate long-term negative impacts.

The Association between Physical Functioning, Symptom Burden, and Coping Strategies with Quality of Life (QOL) in Patients with Chronic Graft-Versus-Host Disease (cGVHD)

Background Allogeneic stem cell transplant survivors with cGVHD experience significant psychological distress and substantial impairments in their QOL. However, the relationship between patients' physical functioning, symptom burden, coping strategies, and QOL over time is currently unknown. Methods We conducted a longitudinal study of patients with moderate to severe cGVHD recruited from a single institution. We assessed patient-reported psychological distress (Hospital Anxiety and Depression Scale), QOL (Functional Assessment of Cancer Therapy- General), physical functioning (Human Activity Profile), cGVHD symptom burden (Lee Symptom Scale), and coping (Coping Inventory for Stressful Situations) at baseline, 3 months, and 6 months. Using mixed linear effects models, we longitudinally examined the relationship between patients' QOL and their physical functioning, cGVHD symptoms, and coping strategies. Results We enrolled 53 patients with moderate (71.7%, 38/53) or severe (28.3%, 15/53) cGVHD. The rate of clinically significant depression and anxiety symptoms at baseline was 32.1% (17/53) and 30.2% (16/33), respectively. Depression and anxiety symptoms did not change substantially over time. Patients reported impaired QOL at baseline [FACT-G: mean=70.33, SD=18.96] which did not change significantly over time [β=-0.66, SE=1.11, P=0.550]. Higher physical functioning was associated with better QOL [β=0.17, SE=0.05, P=0.001] over time, while higher symptom burden was associated with worse QOL [β=-0.38, SE=0.06, P Conclusion Patients with moderate or severe cGVHD report substantial psychological distress and persistently impaired QOL over time. Higher physical function and lower symptom burden are associated with improvement in patients' QOL over time. The use of certain coping strategies was associated with changes in QOL. These data underscore the need for supportive care interventions to promote effective coping and enhance physical functioning in patients with cGVHD.

The association between physical functioning, symptom burden, and coping strategies with quality of life (QOL) in patients with chronic graft-versus-host disease (cGVHD).

178 Background: Allogeneic stem cell transplant survivors with cGVHD experience substantial psychological distress and impairments in QOL. However, the relationship between patients’ physical functioning, symptom burden, coping strategies, and QOL over time is unknown. Methods: We conducted a longitudinal study of patients with moderate-severe cGVHD. We assessed patient-reported psychological distress (Hospital Anxiety and Depression Scale), QOL (Functional Assessment of Cancer Therapy-General), physical functioning (Human Activity Profile), cGVHD symptom burden (Lee Symptom Scale), and coping (Coping Inventory for Stressful Situations) at baseline, 3 months, and 6 months. Using mixed linear effects models, we examined the longitudinal relationship between QOL and physical functioning, cGVHD symptoms, and coping strategies. Results: We enrolled 53 patients with moderate (71.7%, 38/53) or severe (28.3%, 15/53) cGVHD. The rate of clinically significant depression and anxiety symptoms at baseline was 32.1% (17/53) and 30.2% (16/33), respectively, and did not change over time. Patients reported low QOL at baseline [M = 70.33, SD = 18.96], which did not change significantly over time [β = -0.66, SE = 1.11, P = 0.550]. Over time, higher physical functioning was associated with better QOL [β = 0.17, SE = 0.05, P = 0.001], while greater symptom burden was associated with worse QOL [β = -0.38, SE = 0.06, P &lt; 0.001]. While the use of emotion-oriented coping was associated with lower QOL over time [β = -0.70, SE = 0.14, P &lt; 0.001], the use of avoidance-oriented coping was associated with higher QOL over time [β = 0.38, SE = 0.10, P &lt; 0.001]. Task-oriented coping was not associated with psychological distress or QOL. Conclusions: Patients with moderate-severe cGVHD report substantial psychological distress and persistently impaired QOL over time. Higher physical function and lower symptom burden are associated with improved QOL. The use of certain coping strategies was associated with changes in QOL. These data underscore the need for supportive care interventions to promote effective coping and enhance physical functioning in patients with cGVHD.

Adhering to Recommended Lifestyle Changes and Medications 9 Months to 3 Years after Hematopoietic Stem Cell Transplant: Self-Reported Adherence and the Practical, Psychological, and Social Correlates of Adherence

▪Survivors of hematopoietic stem cell transplantation (SCT) must adhere to various lifestyle changes and medication regimens to protect their health and recovery, often for an extended time. Little evidence describes adherence after SCT or correlates of adherence, although evidence from other populations strongly suggests that adherence will be suboptimal for many survivors. To explore these research questions, we conducted secondary analyses on self-reported data from 255 survivors participating in a larger intervention trial. All had undergone stem cell transplant (SCT) (55% autologous, 45% allogeneic) 9 months to 3 years prior to enrollment for a hematologic cancer. After completing baseline measures, they were randomized to one of 4 study arms that varied the writing instructions they were provided as they completed 4 brief writing assignments (1 per week over 4 weeks) in which they wrote about their SCT experience. The 2x2 factorial design crossed whether they used evidence-based instructions for emotionally expressive writing (yes/no) and whether they were told their writing was to be shared with other patients as a form of peer support (yes/no). Writing instructions were not associated with outcomes in the present analyses and are not further described (see Rini et al, 2014). Participants completed a follow-up assessment 3 weeks after the intervention. Collapsing across study arms, we examined participants' self-reports about whether their medical team currently recommended changes to their diet and social activities (e.g., avoiding crowds or ill people), and whether they were currently supposed to be taking medications related to their SCT; because this was not a primary goal of the research, we did not assess what medications they were prescribed. Survivors who reported a recommendation to engage in each behavior also reported the extent to which they were following recommendations on a scale from 1=not at all to 5=completely. A substantial minority of participants reported that their medical team currently recommended changes to their diet (14.2%) and social activities (18.3%), and that they needed to take SCT-related medications (46.5%). Participants who had undergone SCT more recently (fewer weeks since SCT) were more likely to report recommendations to change their social activities (r = -.18, p = .005). Also, compared to autologous SCT survivors, allogeneic SCT survivors were more likely to report recommendations to change their diet (p = .03) and social activities (p = .004), and the need to take medications (p < .001). Only 55.2% of participants who reported being informed of the need to make dietary changes said they were quite a bit or completely adherent (4 or 5 on the response scale). A greater, but still suboptimal, proportion (74.0%) were quite a bit or completely adherent with recommended social activity changes, and 95.8% were quite a bit or completely adherent with medication use (83.9% completely and 11.9% quite a bit). Depending on the medication in question and survivors' definition of being completely versus quite a bit adherent, these findings may indicate cause for concern. Research on solid organ transplant suggests that even small deviations from recommended dosages can influence graft loss or rejection (Dobbels et al., 2010). With respect to correlates of adherence, better physical functioning (SF-36 physical component scores; r = -.33, p = .04) was associated with lower adherence with dietary changes. For social activity changes, having a higher quality relationship with a partner and having more years of education were associated with greater adherence (r = .41, p = .02, and r = .40, p = .01, respectively) whereas having children was associated with lower adherence (r = -.31, p = .03). For medications, better physical functioning was associated with lower adherence (r=-.19, p =.045). Findings suggest that practical, psychological, and social factors may influence adherence to important lifestyle and medication regimens after SCT. They also provide a rationale for larger scale studies using rigorous measures. Using digital platforms/devices to track adherence would provide needed rigor while enabling development of digital coaching interventions to promote sustained behavior change. In the era of consumerization of medicine, it is important to provide evidence to patients that consumerization also means sustained self-engagement to optimize their outcome. DisclosuresMunshi:Kite: Speakers Bureau.

Psychological distress in patients with moderate to severe chronic graft-versus-host disease (cGVHD).

e22137Background: cGVHD is the leading causing of morbidity and mortality in allogeneic stem cell transplant survivors. However, studies assessing psychological distress in patients with cGVHD and ...

The relationship between coping strategies and quality of life (QOL) in patients with chronic graft-versus-host disease (cGVHD).

e19016Background: Allogeneic stem cell transplant survivors with moderate to severe cGVHD experience substantial impairment in their QOL. However, the impact of patients’ physical functioning, symp...

124 - Assessing Needs and Concerns of Autologous and Allogeneic Stem Cell Transplant Survivors at 1-5 Years: A Quality of Life Approach

124 - Assessing Needs and Concerns of Autologous and Allogeneic Stem Cell Transplant Survivors at 1-5 Years: A Quality of Life Approach

Factors influencing the late phase of recovery after bone mineral density loss in allogeneic stem cell transplantation survivors.

Accelerated bone mineral density loss (BMDL) occurs early after allogeneic stem cell transplantation (SCT) and is related to factors such as steroids and chronic GvHD. In order to understand the natural history of BMDL of SCT in the longer term, we evaluated a longitudinal cohort of 148 survivors with a median follow-up of 12 years (range 3-22 years). All women received hormone replacement therapy, and routine calcium/vitamin D supplementation was recommended but ∼50% of patients still had suboptimal vitamin D levels and bisphosphonates were rarely utilized. BMD significantly improved from 5 to 20+ years but the femoral neck and forearm remained vulnerable sites. Younger age, higher pretransplant body mass index (BMI) and increment in BMI post transplant were significantly associated with increased BMD and protected against osteopenia/osteoporosis. These findings support consideration of BMD loss in SCT survivors in two phases, an early phase of BMD loss (3-5 years) followed by a later phase of BMD recovery, with different protective and aggravating factors. Treatment- and transplant-related factors (such as steroids, immunosuppressives, chronic GvHD, vitamin D) are known to impact the early phase of BMD loss but age and BMI are more influential in the late phase of BMD recovery.

Symptom Distress Predicts Long-Term Health and Well-Being in Allogeneic Stem Cell Transplantation Survivors

The number of survivors after allogeneic hematopoietic stem cell transplantation (HSCT) continues to increase, yet their survivorship experience has not been fully characterized. This study examines the health status and health-related quality of life (HRQL) of HSCT survivors. The aims of the study were to: (1) explore the baseline and change over time in these health outcomes, and (2) characterize subgroups experiencing adverse outcomes. In this longitudinal study, adults who survived >3 years from date of allogeneic HSCT completed a series of patient-reported outcome measures annually, including measures of health status, HRQL, and symptoms. Data were analyzed using hierarchical linear modeling. Subjects (N = 171) were on average 44 (±13.5) years of age and primarily male (62.6%); 40% were Hispanic. Mean scores for physical and mental health and HRQL were preserved relative to population norms. Hierarchical linear modeling revealed no significant change in the mean trajectories of these outcomes, although significant between-individual variability was observed. When controlling for demographic and clinical factors, physical symptom distress negatively affected all outcomes. The impact of symptom distress on physical health varied based on time since HSCT; impairment in physical health was greatest in survivors experiencing high symptom distress and who were within the first decade post transplantation. Extended treatment with systemic immunosuppressive therapy also predicted inferior physical health. These findings suggest that patient-centered outcomes are preserved relative to normative values and are generally stable after allogeneic HSCT, although survivors with persistent symptoms and those receiving systemic immunosuppression experience impairments in health status and HRQL.

Post-Transplant Pulmonary Function Abnormalities Nadir At Five Years and Then Fully Normalize by the Second Decade in Allogeneic Stem Cell Transplantation Survivors

Post-Transplant Pulmonary Function Abnormalities Nadir At Five Years and Then Fully Normalize by the Second Decade in Allogeneic Stem Cell Transplantation Survivors

A dedicated GvHD clinic may improve the quality of life for allogeneic stem cell transplant survivors

A dedicated <scp>GvHD</scp> clinic may improve the quality of life for allogeneic stem cell transplant survivors

Chronic Graft Versus Host Disease (GVHD) Does Not Impact Cardiovascular Risk Factors in Survivors of Allogeneic Hematopoietic Stem Cell Transplantation (SCT) up to the Second Decade Post-Transplant,

Abstract 4099Long term survivors of allogeneic SCT have increased risk factors for cardiovascular disease. The reason for this is unclear but chronic GVHD (cGVHD) has been implicated as a potential cause. We prospectively evaluated the impact of cGVHD on cardiovascular risk profiles in 109 allogeneic stem cell transplantation survivors. Transplants were performed at a single center between 1993 and 2006. Sixty-four survivors were informative at 5 years, 45 at > 10 years and 35 at both 5 and 10 years post-transplant. Median ages at transplant, 5 and 10 year follow-up were 34, 40 and 46 years, respectively. There were 62 male and 47 female survivors. Diagnoses at transplant included CML (56), acute leukemia (29), MDS (13), and others (9). Ninety-nine patients received 12–13Gy TBI-based conditioning followed by a 4-log T cell depleted SCT (15 marrow and 84 peripheral blood). Ten patients received non-myeloablative conditioning followed by unmanipulated peripheral blood stem cells. There were clinically relevant increases in prevalence of hypertension (p=<0.001), diabetes (p=0.018), C-reactive protein (CRP) (p<0.001) and Body Mass Index (BMI) (p=0.044) at follow-up compared to baseline (see Table). Dyslipidemias (defined by ATP III criteria) were found in 44% and 52% of 5 and 10 year post-transplant survivors, respectively. At follow-up, 6 of 19 pre-transplant smokers continued to smoke. There was no change in prevalence of any cardiovascular risk factor between the 5 and 10 year time-points. Despite this significant increase in risk factors, clinical cardiovascular events and mortality were uncommon. At the time of analysis, of 12 deaths, only one was due to a cardiovascular cause (cerebrovascular accident). In addition, 2 survivors required percutaneous coronary intervention and one had recurrent pulmonary emboli. Serial electrocardiograms revealed 6 survivors with new ischemic changes and 28 with new rhythm or conduction abnormalities. There was no significant change in left ventricular ejection fraction at follow-up in any survivor compared to their pre-transplant baseline. Of the survivors, 35 had no cGVHD, 18 had cGVHD lasting <3 years and 56 had prolonged cGVHD requiring >3 years of systemic immunosuppression. cGVHD did not exert significant influence on any cardiovascular risk factors at any time-point. This study demonstrates that post-transplant survivors have important and prolonged elevations in cardiovascular risk factors. Although elevations in CRP suggest a persistent chronic inflammatory state, cGVHD was not responsible for the heightened cardiovascular risk profile of these individuals.Percentage of increase in cardiovascular risk factors from pre-transplant baseline at follow-up5yrs (%)10yrs (%)Diabetes8101005Hypertension292563CRP (as a continuous variable)441721BMI (as a continuous variable)210 Disclosures:No relevant conflicts of interest to declare.

Health-related quality of life, symptom distress and sense of coherence in adult survivors of allogeneic stem-cell transplantation.

This is the first Swedish study to evaluate the health-related quality of life and sense of coherence in adult survivors of allogeneic, haematopoietic stem cell transplantation (HSCT). Twenty-five recipients completed three questionnaires 2-4 years after the transplantation. The questionnaires used were the Sickness Impact Profile (SIP), the Symptom Frequency Intensity and Distress (SFID-BMT) scale and the Sense of Coherence (SOC) scale measuring subjective functional status, symptom distress and coping ability. Impairments in functional status were found, as compared with a population norm. The most common impairments were found in the areas of social interaction and sleep and rest. Eye problems, dry mouth, cough, sexual problems, tiredness, anxiety and changes of taste were symptoms reported by more than half of the patients. Despite impaired functioning and a high incidence of symptoms, the general health was described as quite good or excellent by 80% (n = 20) of the patients. The majority (20/22) had also been able to return to work or to attend school. No difference in the sense of coherence was seen, as compared with the population norm. Functional impairments were significantly correlated to a lower degree of sense of coherence.