Hospitalization For Hematopoietic Stem Cell Transplantation Research Articles

Abstract 4137644: Association of Prolonged QTc with Development of Heart Failure after Hematopoietic Stem Cell Transplantation

Background: Use of hematopoietic stem cell transplantation (HSCT) continues to rise in the United States, particularly in older age groups; however, HSCT is associated with various cardiovascular complications including heart failure (HF). We sought to examine whether prolonged QTc prior to HSCT was associated with the risk of HF post-HSCT. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center (RUMC) between 2008-2019. In this analysis, only patients from the UMHS site were included (n=2,435). Baseline electrocardiogram (EKG) data were recorded prior to transplant (median (IQR) 14 (3, 30) days). QTc prolongation was defined per CTCAE grading criteria as Normal (<440ms), Grade 1 (440-480ms), and Grade ≥2 (>480ms). The primary outcome was new-onset HF defined as a diagnosis documented by health care providers after the date of hospitalization for HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT cardiovascular risk score. Results: Of the 2,435 patients (mean age at HSCT 55±13.4 years; 59.7% male; 90.5% White), 534 (21.9%) had long QTc pre-HSCT. Of those, 440 were Grade 1 and 94 were Grade ≥2. In all, 138 HF events occurred over median period of 2.3 (1.0-5.3) years. The 5-year cumulative incidence of HF was 5.0% in patients with normal QTc, 8.4% in patients with Grade 1 QTc prolongation, and 19.0% in patients with Grade ≥2 QTc prolongation (Figure). Patients with Grade 1 and Grade ≥2 prolongation had a 1.57 (95% CI: 1.05, 2.33) and 2.71 (95% CI: 1.51, 4.86) times higher risk of HF, respectively, compared to those with normal QTc. Conclusions: In this contemporary cohort of adult HSCT patients, those with QTc prolongation prior to HSCT had a higher incidence of HF compared to normal QTc, with greater degree of prolongation associated with higher risk. These findings highlight the importance of accounting for the QTc as part of the pre-transplant cardiovascular evaluation

A Peer Support Intervention in Patients With Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation (HSCT): The STEPP Proof-of-Concept Trial

Although peer support interventions are associated with improved patient-reported outcomes in diverse cancer populations, structured peer support programs tailored to the needs of patients undergoing hematopoietic stem cell transplantation (HSCT) are lacking. This single-arm, proof-of-concept trial aimed to refine the Supporting Transplant Experiences with Peer Program (STEPP), a structured, five-session, manualized, phone-delivered peer support intervention for patients undergoing HSCT, informed by qualitative feedback from patients. Adult patients with hematologic malignancies scheduled to undergo allogeneic or autologous HSCT were eligible to participate in the study approximately two weeks prior to their HSCT hospitalization. Participants received the STEPP intervention, which focused on providing informational, emotional, and practical support. To refine the intervention, we conducted semi-structured qualitative exit interviews to gather feedback on the content of STEPP and to identify facilitators and barriers to engagement. Transcribed interviews were analyzed using rapid analytic methods by two coders. Of the 37 eligible patients, 25 enrolled in the study, 20 completed all intervention sessions and 20 completed exit interviews. Participants highlighted that discussions with peer mentors/STEPP interventionists about the transplant journey and processing information provided by the clinical team were the most valuable aspects of STEPP. Positive experiences during the first intervention session facilitated patient engagement with the program. Potential barriers to engagement included logistical challenges in connecting with interventionists while experiencing physical symptoms during inpatient hospitalization and being paired with an interventionist who had a different cancer diagnosis and/or type of transplant. Patients undergoing HSCT reported positive experiences with the structured five-session, phone-delivered peer support intervention administered before and during the HSCT hospitalization. Patients’ descriptions of barriers and facilitators to engagement with the STEPP intervention underscore the importance of patient input and programmatic structure in peer support interventions for this population. Insights from this proof-of-concept trial will be incorporated into future trials of STEPP to improve outcomes in HSCT recipients.

Multi-Site Randomized Trial of Inpatient Palliative Care for Hospitalized Patients Undergoing Hematopoietic Stem Cell Transplantation

Background: Patients with hematologic malignancies experience a substantial decline in their quality of life (QOL) and psychological health during their hospitalization for hematopoietic stem cell transplantation (HSCT). Early single center studies established the feasibility and promising preliminary efficacy of integrating palliative care during the HSCT hospitalization. However, data to test the efficacy of this care model across diverse care settings are lacking. Methods: We conducted a multi-site randomized trial among 360 adults with hematologic malignancies undergoing autologous or allogeneic HSCT at three academic institutions. Patients were randomly assigned to an inpatient palliative care intervention (n= 180) versus usual care (n=180), stratified by study site and type of HSCT. Intervention participants met with a palliative care clinician at least twice weekly during the HSCT hospitalization to address their physical and psychological symptoms. Patients assigned to usual care received all supportive care measures provided by the HSCT team and could be seen by palliative care upon request. We assessed patient QOL (Functional Assessment of Cancer Therapy (FACT) - Bone Marrow Transplant), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), post-traumatic stress (PTSD) symptoms (PTSD Checklist), symptom burden (Edmonton Symptom Assessment Scale-Revised), and fatigue (FACT-Fatigue, higher scores indicate lower fatigue) at baseline and week-2 during hospitalization. The primary endpoint was QOL at week-2 during the HSCT hospitalization when patients typically experience their QOL nadir during HSCT. We used analysis of covariance, adjusting for baseline scores, to evaluate the effect of the intervention on patient-reported outcomes at week-2. Results: We enrolled 69.5% (360/518) of eligible patients (mean age = 55.4 (SD=12.5), 61.9% male, 76.6% White, 23.4% racial minorities, 8.7% Hispanic ethnicity, and 50.2% underwent allogeneic HSCT) between October 2018 and July 2022. Compared to those receiving usual care, participants receiving the inpatient palliative care intervention reported better QOL (95.5 vs. 89.3, P<0.001), and lower depression (5.9 vs. 6.9, P=0.041) and PTSD symptoms (26.0 vs. 28.2, P = 0.022) at week-2. Intervention participants also reported lower symptom burden (35.3 vs. 40.1, P=0.018) and better fatigue scores (28.6 vs. 25.6, p=0.014) compared to those assigned to usual care at week-2 during HSCT hospitalization. Anxiety symptoms (HADS-A) did not demonstrate a measurable difference between the two groups at week-2 during HSCT. Conclusions: In this multi-site randomized clinical trial, inpatient palliative care led to substantial improvements in patients' QOL, depression and PTSD symptoms, symptom burden, and fatigue during HSCT hospitalization compared to usual care. Integrated palliative care should be considered a new standard of care for patients hospitalized for HSCT.

Quality of Life, Physical Functioning, and Psychological Distress of Older Adults Undergoing Hematopoietic Stem Cell Transplantation

With advances in therapies for hematologic cancers, older adults increasingly undergo hematopoietic stem cell transplantation (HSCT). Older adults may potentially experience an exaggerated burden of toxicity from HSCT. Studies examining the quality of life (QOL), physical functioning, and psychological symptom trajectory for older adults undergoing HSCT are limited. Our primary aim was to describe the trajectory of QOL, physical functioning, and psychological distress of older adults undergoing HSCT. Secondarily, we aimed to compare the trajectory of QOL, physical functioning, and psychological distress of older and younger adults undergoing HSCT and to evaluate factors associated with QOL trajectory in older adults undergoing HSCT. We conducted secondary analyses of two prospective studies conducted at Massachusetts General Hospital. From 2011 to 2016, we enrolled 250 adults undergoing allogeneic or autologous HSCT. Older age was defined as age ≥65 years. We collected patient-reported outcomes (PROs) within 72 hours of admission for HSCT, at hematologic nadir (2 weeks), and at 6 months after HSCT. To assess QOL, physical functioning, and psychological symptoms, we used the Functional Assessment of Cancer Therapy (FACT)–Bone Marrow Transplant, FACT-Trial Outcome Index, and Patient Health Questionnaire–9, respectively. We used the post-traumatic stress disorder (PTSD) Checklist–Civilian Version to assess PTSD symptoms. We fit linear mixed effects models to characterize trajectories of changes in PROs across timepoints and to evaluate baseline factors associated with QOL trajectories in older adults. Overall 30.4% (76/250) of our cohort was 65 years or older. All older adults undergoing allogeneic HSCT received a reduced intensity conditioning regimen. At 2 weeks after HSCT, older patients experienced a decline in QOL (Δ = −16.6, P < .001), physical functioning (Δ = −15.4, P < .001) and an increase in depression symptoms (Δ = 3.8, P < .001). At 6 months after HSCT, QOL (Δ = 1.4, P = .7), physical functioning (Δ = 1.7, P = .5), and depression symptoms (Δ = 0.4, P = .6) recovered to baseline values. At 6 months after HSCT, the proportion of older patients with PTSD symptoms increased from 5.3% (4/76) at baseline to 13.2% (10/76). There was no significant difference in slopes or trajectories of PROs between older and younger patients. In older adults, baseline psychological distress was associated with significantly worse QOL trajectory (Δ= −21.6, P ≤ .001). Older adults experienced a sharp decline in QOL and physical functioning and an increase in depression symptoms within 2 weeks of HSCT hospitalization. Baseline psychological distress was associated with a pronounced worsening in post-HSCT QOL trajectory. These findings underscore the need for supportive care interventions to improve the experience of older adults undergoing HSCT.

High-dose Chemotherapy Impairs Cardiac Autonomic Control of Hospitalized Cancer Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Autologous hematopoietic stem cell transplantation (HSCT) patients have intermediary and late cardiac autonomic dysfunction, which is an independent mortality predictor. However, it is unknown when this HSCT-related autonomic dysfunction begins during hospitalization for HSCT and whether cardiac autonomic control (CAC) is related to cardiotoxicity in these patients. CAC was assessed in 36 autologous-HSCT inpatients (HSCT group) and 23 cancer-free outpatients (CON group) using heart rate variability analysis. The HSCT group was assessed at five time-points from admission to hospital discharge during hospitalization period. The CON group was assessed once. The severity of cardiotoxicity (CTCAE 5.0) and cardiac troponin I were recorded. The CAC was significantly reduced after high-dose chemotherapy (HDC) (reduction of MNN, SDNN, RMSSD, LFms2 and HFnu, and increase of LFnu and LF/HF; P<0.05). At the onset of neutropenia, pNN50 and HFms2 were also reduced (P<0.05) compared to the admission ones. Although both groups were similar regarding CAC at hospital admission, the HSCT patients showed impaired CAC at hospital discharge (P<0.05). The LF/HF was positively associated with cardiac troponin I and RMSSD was inversely associated with the severity of cardiotoxicity (P≤0.05). CAC worsened during hospitalization for autologous-HSCT, mainly after HDC. In addition, it seems associated to early signs of cardiotoxicity in these patients.

G-CSF Improves Stable Engraftment in Adults with Sickle Cell Disease Undergoing Nonmyeloablative Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative in patients with sickle cell disease (SCD). HSCT using nonmyeloablative conditioning leads to a mixed chimerism that improves the SCD phenotype but may be complicated by the continued need for immunosuppression and graft loss. Granulocyte colony stimulating factor (G-CSF) may stimulate progenitor cells and is used post-HSCT to reduce the duration of neutropenia and the risk of neutropenic fever. G-CSF has been generally avoided in patients with SCD due to its risk of promoting vaso-occlusion (PMID 19513902). Starting in 7/2016, our institution administered G-CSF after day +5 post-HSCT on the days when the ANC was < 500 x103/µL. In this study, we evaluated whether G-CSF is safe and can improve the duration of neutropenia, infection risk, and donor chimerisms in adults with SCD undergoing non-myeloablative HSCT. We included 34 adults with SCD that underwent allogeneic HSCT from an HLA-matched sibling donor in our institution and were conditioned with alemtuzumab and total body irradiation (TBI) (PMID 33534948) between 11/2011 and 8/2021. Medical records were individually reviewed for data extraction. Linear and categorical outcomes were compared by G-CSF use with the Kruskal-Wallis and chi-square test, respectively. We also compared the Kaplan-Meier curves for discontinuation of immunosuppression with the log-rank method. Median and interquartile range (IQR) are provided. The median age of our cohort was 33 years (IQR, 26 - 45 years), 18 (53%) patients were female, and 30 (88%) had hemoglobin SS genotype. We did not observe statistically significant differences in baseline characteristics between the SCD patients that received G-CSF versus did not receive G-CSF for median age (37 years vs. 32 years), female gender (69% vs. 43%), hemoglobin SS genotype (85% vs. 90%) or median CD34+ dose (8.6 vs. 8.1 x 106/kg), respectively. In the 13 SCD patients that received G-CSF, the median day when it was initiated was day +10 (IQR, 7 - 17) and for a median of 3 days (IQR, 2 - 7 days). The maximum pain score during hospitalization was not significantly different in the SCD group that received G-CSF (median 8, IQR, 7 - 10) compared to those that did not receive G-CSF (median 10, IQR, 9 - 10). Median time to neutrophil engraftment (G-CSF: day 16 vs. no G-CSF: day 22) and duration of neutropenia (G-CSF: 7 days vs. no G-CSF: 9 days) were relatively similar between the 2 groups, while the incidence of neutropenic fevers trended lower with G-CSF treatment (8% vs. 29%, respectively, P=0.1). Whole blood or myeloid chimerism values were significantly higher in the SCD patients that received G-CSF at day +30, +90, +180, and 1 year post-HSCT (Figure 1A). Secondary graft loss was not observed after we implemented G-CSF while 4 out of 21 (19%) of patients experienced secondary graft failure who did not receive post-HSCT G-CSF. Furthermore, in those patients with stable engraftment, we observed a trend for more patients who received G-CSF being successfully tapered off immunosuppression (11/13, 85%) versus those that did not receive G-CSF (10/17, 59%) (Figure 1B). In conclusion, administration of G-CSF to patients with SCD undergoing HSCT conditioned with alemtuzumab/TBI was associated with significantly higher whole blood or myeloid donor chimerism values. This benefit was achieved without a significant increase in pain scores during the hospitalization for HSCT and was associated with trends for a greater proportion of patients discontinuing immunosuppression and less secondary graft loss. Future studies investigating the effects of G-CSF on donor myeloid progenitor cells and on T-cell clearance may guide strategies to improve outcomes for curative therapies in adults with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Exercise Interventions During Hospitalization for Stem Cell Transplantation: An Integrative Review.

Exercise interventions may influence adverse effects experienced during hospitalization for hematopoietic stem cell transplantation (HSCT). Adherence to exercise interventions is challenging. This review aimed to synthesize the literature to identify exercise interventions implemented during hospitalization for HSCT, including intervention characteristics, adherence, barriers and facilitators, and behavior change techniques using the behavior change technique taxonomy. A review of PubMed, CINAHL, PsycINFO, and Embase was completed. The sample included 19 studies. Exercise interventions demonstrated heterogeneity in prescription components, definitions, measures, and reporting of adherence. Barriers and facilitators of adherence to exercise were reported infrequently. Behavior change techniques most frequently used in studies reporting adherence rates of ≥75% included instruction on how to perform the behavior, graded tasks, and adding objects to the environment. The heterogeneity in definitions and measures of adherence limit forming conclusions to identify barriers and facilitators and determine which behavior change techniques increase adherence to exercise during HSCT.

Peer support in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT): a qualitative study.

Peer support, a distinctive form of social support in which patients share emotional, social, and practical help based on their own lived experience of illness and treatment, positively impacts patient-reported outcomes in cancer populations. However, data on peer support experiences among hematopoietic stem cell transplant (HSCT) recipients are limited. We conducted semi-structured qualitative interviews among 12 allogeneic HSCT recipients who were ≤6 months post transplant without any complications and 13 allogeneic HSCT recipients >6 months post transplant and living with chronic graft-versus-host disease. Interviews explored patients’ experiences with peer support and their preferences for a peer support intervention tailored to the needs of HSCT recipients. While the majority (70%) of participants reported no formal experience with peer support, most (83%) articulated themes of potential benefits of peer support (e.g., managing expectations and uncertainty that accompany HSCT). Most participants (60%) reported a preference for a peer support intervention prior to the HSCT hospitalization. Despite the limited data on peer support interventions among HSCT recipients and lack of formal peer support experience in most of our cohort, our study shows that HSCT recipients clearly acknowledge the potential benefits of a peer support intervention, and they prefer that it start prior to transplantation.

Economic Burden of Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Acute Lymphoblastic Leukemia (ALL) in the US

IntroductionAcute lymphoblastic leukemia (ALL) is a rare disease that affects lymphoblasts derived from lymphoid stem cells and due to the acute nature of this cancer, it is rapidly fatal without treatment (National Cancer Institute, 2016). The average 5-year overall survival (OS) rate was 35% for adult ALL and over 90% of the relapsed or refractory patients eventually die with a median OS of 3-6 months (Kantarjian HM et al. 2010, Bassan and Hoelzer 2011, Forman and Rowe 2013). Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for patients with B-cell ALL. Previous studies find that HSCT is associated with high costs and healthcare resource use. However, there is no study examining the allogeneic HSCT costs specifically for the adult ALL patients.ObjectiveThe aim of this study is to quantify the economic burden of allogeneic HSCT for adult B-cell ALL patients and relapsed adult B-cell ALL patients in the US.MethodsThis was a retrospective cohort study using Truven Health MarketScan® Commercial and Medicare Supplemental Databases. Patients with ≥1 inpatient claims or ≥2 non-diagnostic outpatient claims at least 30 days apart for any ALL diagnosis (ICD-9-CM 204.00-204.02, ICD-10-CM C91.00-C91.02) during 4/1/2009 - 10/31/2016 were extracted. All patients were required to have ≥1 hospitalization with diagnosis-related group in 834-839 on or after the first ALL diagnosis, have ≥1 allogeneic HSCT hospitalization (index date is the admission date for the initial HSCT hospitalization), are ≥18 years old on index date, and have ≥6 months of continuous enrollment prior to index date. Patients with medications for T-Cell ALL during the study period were excluded. Relapsed ALL patients were required to have ≥1 inpatient claims or ≥2 non-diagnostic outpatient claims at least 30 days apart for relapsed ALL diagnosis (ICD9: 204.02, ICD10: C91.02). Patients were followed until the earliest of inpatient death, end of continuous enrollment, or end of the study period (10/31/2016). Outcomes included all-cause and HSCT-related costs and total hospital length of stay (LOS) observed during the index hospitalization, and during 100, 180, or 365 days post-index periods (for the subset of patients with at least 100, 180, or 365 days of continuous enrollment after index date or an inpatient death during that follow-up). The costs for the HSCT-related complications such as graft versus host disease (both acute and chronic), hepatic veno-occlusive disease (VOD), graft failure, serious infections, bronchiolitis obliterans, secondary malignancies, and inpatient death were included, as well as the costs for transplant conditioning regimens during the 14 days before HSCT. Costs were sum of the plan paid amount and out-of-pocket amount in 2016 dollars. All descriptive analyses were conducted for patients with ALL (including both frontline and relapsed ALL) and relapsed ALL, separately.ResultsA total of 692 ALL patients (mean age: 45.6; male: 56.1%; mean Charlson comorbidity index: 3.2) were identified. Among all the ALL patients, 123 had relapsed ALL. Among ALL patients, mean (SD; median) costs were $275,642 ($316,109; $212,742) and mean (SD) LOS was 31.1 (20.9) days during the initial HSCT hospitalization (Table 1). During the first year post index, mean (SD; median) all-cause and HSCT-related costs were $543,146 ($416,148; $455,245) and $394,069 ($378,893; $301,977), respectively, with all-cause and HSCT-related mean (SD) LOS of 52.5 (41.5) and 49.2 (40.3) days. Among relapsed ALL patients, mean (SD; median) costs were $319,643 ($310,479; $255,545) during the initial HSCT hospitalization (Table 2). Mean (SD; median) all-cause and HSCT-related costs were $680,503 ($651,399; $556,244) and $535,245 ($577,152; $395,031) during the first year post index. Mean (SD) LOS was 33.9 (18.0) days during the initial HSCT hospitalization and 61.5 (46.4) and 59.1 (45.8) days during the first year post index for all-cause and HSCT-related hospital stays, respectively. The initial HSCT hospitalization accounts for about 47% and 51% of the total costs in the first year after HSCT for ALL and relapsed ALL patients, respectively.ConclusionsAllogeneic HSCT in ALL is associated with substantial economic burden, especially among relapsed ALL patients. During the first year post HSCT, about half of the total costs occurred during the initial HSCT hospitalization. [Display omitted] DisclosuresZhang:Amgen Inc.: Employment, Equity Ownership. Cong:Amgen Inc.: Employment, Equity Ownership.

Post-Traumatic Stress Symptoms in Hematopoietic Stem Cell Transplant Recipients

Hematopoietic stem cell transplantation (HCT) is an intensive and potentially curative therapy for patients with hematologic malignancies. Patients admitted for HCT experience a prolonged, isolating hospitalization and endure substantial physical and psychological symptoms. However, there is a paucity of research on the impact of HCT on post-traumatic stress disorder (PTSD) symptoms in transplant recipients. This secondary analysis of 250 patients who underwent autologous and allogeneic HCT examined PTSD using the PTSD Checklist-Civilian measured at 6 months after HCT. We used the Functional Assessment of Cancer Therapy-Bone Marrow Transplant, and the Hospital Anxiety and Depression Scale to assess quality of life (QOL) and depression and anxiety symptoms at the time of admission for HCT, week 2 during hospitalization, and 6 months after HCT. We used multivariate regression models to assess factors associated with PTSD symptoms. Given collinearity between QOL, depression, and anxiety symptoms, we modeled these separately. The rate of clinically significant PTSD symptoms at 6 months after HCT was 18.9% (39/206). Participants with clinically significant PTSD symptoms experienced hypervigilance (92.3%), avoidance (92.3%), and intrusion (76.9%) symptoms. Among patients without clinically significant PTSD symptoms, 24.5% had clinically significant hypervigilance symptoms and 13.7% had clinically significant avoidance symptoms. Lower QOL at time of HCT admission (B=-0.04, P=.004) and being single (B=-3.35, P=.027) were associated with higher PTSD symptoms at 6 months after HCT. Higher anxiety at time of HCT admission (B=1.34, P <.001), change in anxiety during HCT hospitalization (B=0.59, P =.006), and being single (B=-3.50, P=.017) were associated with higher PTSD symptoms at 6 months. In a separate model using depression, younger age (B=-0.13, P=.017), being single (B=-3.58, P=.018), and higher baseline depression symptoms were also associated with higher PTSD symptoms at 6 months (B=0.97, P < .001). Approximately one fifth of patients undergoing HCT experience clinically significant PTSD symptoms at 6 months after transplantation. The prevalence of hypervigilance and avoidance symptoms are notable even among patients who do not have clinically significant PTSD symptoms. Interventions to prevent and treat PTSD symptoms in HCT recipients are clearly warranted.

Tailored Exercise during Hematopoietic Stem Cell Transplantation Hospitalization in Children with Cancer: A Prospective Cohort Study.

Simple SummaryThe use of hematopoietic stem cell transplantation (HSCT), particularly among children, has increased over the last decades. However, it is frequently associated with a high risk of morbidity and mortality, and HSCT-related adverse effects can potentially impair survivors’ health status. We aimed to assess the effects on major clinical outcomes of a supervised exercise intervention performed by children with cancer during hospitalization for HSCT. The main finding of this prospective study in a quite large cohort of pediatric HSCT recipients (n = 118, aged 4–18 years) is that a moderate intensity supervised exercise program (aerobic + resistance exercises) performed from the beginning of the conditioning phase for HSCT until the end of the neutropenic phase is safe and well tolerated and tends to decrease risk of infections after allogeneic HSCT, as compared with not performing the program.We assessed the clinical effects of a supervised exercise (aerobic + resistance) intervention performed during inpatient hospitalization for pediatric hematopoietic stem cell transplantation (HSCT). Patients were placed in an exercise (n = 65 (47 and 18 with allogeneic (allo-) and autologous (auto-) HSCT, respectively)) or a control (n = 53 (39 and 14)) group. Exercise interventions were performed in isolated hospital patient rooms. Patients were followed-up from the beginning of the conditioning phase up to 6 years. We assessed survival, risk of graft-versus-host disease (GvHD) or graft failure (primary outcomes), and engraftment kinetics, supportive care, toxicity profile, and immune reconstitution for auto-HSCT and allo-HSCT. The exercise intervention was safe and did not affect the risk of mortality, acute/chronic GvHD, or graft failure (all p > 0.05). No between-group differences (p > 0.05) were found for the remainder of clinical endpoints, except for a reduced number of total and viral infections in the exercise group after allo-HSCT (unadjusted p = 0.005 for both total and viral infections, and adjusted p = 0.023 and 0.083, respectively). In conclusion, exercise performed during inpatient hospitalization for pediatric HSCT is safe and well tolerated during both auto and allo-HSCT and tends to decrease the risk of infection after allo-HSCT. These findings provide additional support to the notion that a multidisciplinary approach (i.e., including the work of exercise specialists) is suitable in the management of children undergoing HSCT. Further studies are needed to determine whether applying a different training stimulus (notably, higher exercise intensities) exerts positive effects on HSCT prognosis in these patients.

Reactivation of human herpesvirus 6 in pediatric allogeneic hematopoietic stem cell transplant recipients.

Reactivation of human herpesvirus 6 (HHV-6) occurs in 30%-50% of patients (pts) who receive allogeneic (allo) hematopoietic stem cell transplant (HCT). However, the recommendation for post-transplant HHV-6 monitoring and treatment in pediatric pts is not well established. HHV-6 incidence rates and the clinical outcomes were reported for 139 pediatric pts (≤18years) undergoing first allo-HCT at City of Hope from July 2011 to July 2017, for whom HHV-6 was monitored weekly throughout HCT hospitalization. For 57 pediatric pts, who underwent first HCT from January 2009 to July 2011, HHV-6 was tested as clinically indicated and only rates of HHV-6 viremia were collected. From July 2011 to July 2017, HHV-6 was detected in 88/139 pts (63%). The frequency of HHV-6 viremia was associated with malignant diagnoses, myeloablative conditioning, and cord blood HCT. Treatment with antiviral agents was offered to symptomatic pts with a higher viral load (VL), for whom the time to VL clearance was longer and the frequency of subsequent recurrences was higher. Pts with a lower VL cleared HHV-6 without treatment. HHV-6 viremia was associated with a higher frequency of grade II-IV acute graft-versus-host disease (GVHD) (P=.022), but did not affect overall survival (OS), disease-free survival (DFS), non-relapsed mortality (NRM), myeloid, or platelet (Plt) engraftment. HHV-6 weekly screening is not necessary for all HCT pts but may be considered for high-risk pts with malignant diagnoses undergoing cord blood HCT; otherwise, HHV-6 should be tested as clinically indicated. Only symptomatic pts (especially with a high VL>25000) could benefit from treatment. HHV-6 viremia at the time of initiation and administration of the conditioning regimen cleared promptly without the need to augment the transplant process.

Design of a randomized placebo controlled trial of high dose intravenous thiamine for the prevention of delirium in allogeneic hematopoietic stem cell transplantation

BackgroundDelirium is a highly prevalent and preventable neuropsychiatric condition with major health consequences. Thiamine deficiency is a well-established cause of delirium in those with chronic, severe alcoholism, but there remains an underappreciation of its significance in non-alcoholic populations, including patients with cancer. Treatment of suspected thiamine-related mental status changes with high dose intravenous (IV) thiamine has preliminary evidence for improving a variety of cognitive symptoms in oncology inpatient settings but has never been studied for the prevention of delirium in any population. ObjectivesThe primary objective of this clinical trial is to determine if high dose IV thiamine can prevent delirium in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for treatment of cancer. Secondary objectives are to determine if thiamine status is predictive of delirium onset and if high dose IV thiamine can attenuate the deleterious impact of delirium on health-related quality of life (HRQOL), functional status, and long-term neuropsychiatric outcomes. MethodsIn this phase II study, we are recruiting 60 patients undergoing allogeneic HSCT, randomizing them to treatment with high dose IV thiamine (n = 30) versus placebo (n = 30), and systematically evaluating all participants for delirium and related comorbidities. We use the Delirium Rating Scale to measure the severity and duration of delirium during hospitalization for HSCT. We obtain thiamine levels weekly during the transplantation hospitalization. We assess HRQOL, functional status, depression, post-traumatic stress symptoms, and cognitive function prior to and at one, three, and six months after transplantation.

Post-traumatic stress symptoms in hematopoietic stem cell transplant (HCT) recipients.

7505 Background: Patients admitted for HCT, an intensive and potentially curative therapy for hematologic malignancies, experience a prolonged, isolating hospitalization and endure substantial physical and psychological symptom burden. However, data are limited regarding long-term post-traumatic stress (PTSD) in HCT survivors and its risk factors. Methods: We conducted a secondary analysis examining longitudinal data from 250 patients who underwent autologous and allogenic HCT. We used the Post-Traumatic Stress Checklist (PTSD-CL) to assess for PTSD symptoms at six months post-HCT. We used the Functional Assessment of Cancer Therapy—Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale to assess quality of life (QOL), depression, and anxiety symptoms at the time of admission for HCT, at week-2 during hospitalization, and at six months post-HCT. We used multivariate regression models to assess factors associated with PTSD symptoms, modeling QOL, depression, and anxiety symptoms separately given their collinearity. Results: The mean age was 56.3 (SD = 13.3). The rate of clinically significant PTSD symptoms at six months post-HCT was 18.9% and these patients experienced hypervigilance (92.3%), avoidance (92.3%), and intrusion (76.9%) symptoms. Among patients without clinically significant PTSD symptoms, 24.5% and 13.7% had clinically significant hypervigilance and avoidance symptoms, respectively. Lower QOL at time of HCT admission (B = -0.04, P = 0.004), and being single (B = -3.35, P = 0.027) were associated with higher PTSD symptoms at six months post-HCT. Higher anxiety at time of HCT admission (B = 1.34, P &lt; 0.001), change in anxiety during HCT hospitalization (B = 0.59, P = 0.006), and being single (B = -3.50, P = 0.017), were associated with higher PTSD symptoms at six months. In a separate model, younger age (B = -0.13, P = 0.017), being single (B = -3.58, P = 0.018), and higher baseline depression symptoms were also associated with higher PTSD symptoms at six months (B = 0.97, P &lt; 0.001). Conclusions: Approximately one fifth of patients undergoing HCT experienced clinically significant PTSD symptoms at six months post-transplant. Patients’ baseline QOL and psychological symptoms emerged as important predictors of their risk for PTSD at six months post-HCT. Thus, interventions to prevent and treat PTSD symptoms in HCT recipients are clearly warranted.

Microbiology and Risk Factors for Hospital-Associated Bloodstream Infections Among Pediatric Hematopoietic Stem Cell Transplant Recipients.

BackgroundChildren undergoing hematopoietic stem cell transplantation (HSCT) are at high risk for hospital-associated bloodstream infections (HA-BSIs). This study aimed to describe the incidence, microbiology, and risk factors for HA-BSI in pediatric HSCT recipients.MethodsWe performed a single-center retrospective cohort study of children and adolescents (<18 years of age) who underwent HSCT over a 20-year period (1997–2016). We determined the incidence and case fatality rate of HA-BSI by causative organism. We used multivariable Poisson regression to identify risk factors for HA-BSI.ResultsOf 1294 patients, the majority (86%) received an allogeneic HSCT, most commonly with umbilical cord blood (63%). During the initial HSCT hospitalization, 334 HA-BSIs occurred among 261 (20%) patients. These were classified as gram-positive bacterial (46%), gram-negative bacterial (24%), fungal (12%), mycobacterial (<1%), or polymicrobial (19%). During the study period, there was a decline in the cumulative incidence of HA-BSI (P = .021) and, specifically, fungal HA-BSIs (P = .002). In multivariable analyses, older age (incidence rate ratio [IRR], 1.03; 95% confidence interval [CI], 1.01–1.06), umbilical cord blood donor source (vs bone marrow; IRR, 1.69; 95% CI, 1.19–2.40), and nonmyeloablative conditioning (vs myeloablative; IRR, 1.85; 95% CI, 1.21–2.82) were associated with a higher risk of HA-BSIs. The case fatality rate was higher for fungal HA-BSI than other HA-BSI categories (21% vs 6%; P = .002).ConclusionsOver the past 2 decades, the incidence of HA-BSIs has declined among pediatric HSCT recipients at our institution. Older age, umbilical cord blood donor source, and nonmyeloablative conditioning regimens are independent risk factors for HA-BSI among children undergoing HSCT.

The use of low doses of methotrexate during peri-cell infusion period may be a risk factor for acute kidney injury in patients subjected to hematopoietic stem cell transplantation.

Acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) is associated with high mortality rates. To determine the incidence and risk factors associated with AKI in patients undergoing HSCT during the infusion period, patients admitted for HSCT from 2012 to 2015 were studied. AKI was classified according to the KDIGO (Kidney Disease Improving Global Outcomes) criteria. We analyzed the main comorbidities, underlying conditions, types of transplant, preparative regimens, and use of potentially nephrotoxic drugs as risk factors for AKI. Among the 180 patients (median age 53years), 69 (36.5%) developed AKI (23 KDIGO 1, 28 KDIGO 2, and 18 KDIGO 3), 49 (50.0%) undergoing allogeneic and 20 (22.3%) autologous transplantation, and 18 (9.4%) required dialysis. The main comorbidities were hypertension (38; 19.8%), and diabetes (19; 9.9%). The median pre-transplant creatinine was 0.7mg/dl. Twenty-one patients died (10.9%). The risk factors for AKI in allogeneic HSCT were as follows: baseline estimated glomerular filtration rate (eGFR) (RR 1.12 (1.02-1.22), p = 0.019), use of vasopressors (RR 3.72 (2.20-6.29), p < 0.001), and use of methotrexate (RR 1.83 (1.08-3.11), p = 0.025). Male gender (RR 5.91 (1.65-21.16), p = 0.006), baseline eGFR (RR 1.22 (1.04-1.43), p = 0.011), and use of aminoglycosides (RR 3.92 (1.06-14.44), p = 0.041) were the risk factors for AKI associated with autologous HSCT. During hospitalization for HSCT, AKI was a common problem. The use of a low dose of methotrexate to prevent graft versus host disease was associated with its occurrence.

Morbidity, Mortality, and Healthcare Utilization in a National Cohort of Pediatric Patients with Hemophagocytic Lymphohistiocytosis Who Received Hematopoietic Stem Cell Transplant

Background Hemophagocytic lymphohistiocytosis (HLH) is a severe life threatening hyper-inflammatory syndrome of abnormal immune activation and dysregulation if untreated. The 5-year probability of survival (pSu) obtained from HLH registries and treatment protocols HLH-94 and HLH-2004 ranges from 21%-64%, with improved 5-year pSu of up to 70% following hematopoietic stem cell transplant (HSCT) (Arico et al., Trottestam et al., Bergsten et al.). Despite significant advances in the management of HLH over time, survival remains low and the extent of disease morbidity and healthcare utilization is poorly characterized. In this study, we sought to investigate morbidity, mortality, and the healthcare burden in children and adolescents with HLH who underwent HSCT. Methods Using the Pediatric Health Information System (PHIS) database, we identified patients under the age of 21 years admitted between 01/01/2004 and 09/30/2018 with a primary or secondary ICD-9 or ICD-10 diagnosis codes for HLH, as well as concurrent medication charges for both dexamethasone and etoposide in the same encounter. We then identified the patients who underwent HSCT to further analyze them. We abstracted data on demographics, hospitalizations, HSCT related complications, mortality, resource utilization and costs. Results were summarized using descriptive statistics. Time to HSCT was calculated as elapsed time from the admission date of the initial encounter to the date of the encounter in which there was a procedure code for HSCT. Time to mortality event was calculated as elapsed time from the admission date of the initial encounter to the discharge date of the encounter in which mortality occurred. The PHIS database provides an encrypted patient medical record number; thus, we were able to follow patients over time. This allowed for a better visualization of the patient's hospitalizations trend over 14 years. Results A total of 493 patients met inclusion criteria for HLH during the study period from 52 children's hospitals. The majority of patients (n = 284, 58%) were less than 5 years of age. Of these, 136 patients (28%) underwent HSCT with 155 hospital encounters, including readmissions. The median age at the time HSCT was 2 years (IQR; 0-9 years) and there were 82 males (60%). The median time to HSCT was 126 days (IQR: 75-193 days) and the average length of stay for the initial HSCT hospitalization was 61.1 days. Median initial HSCT hospitalization cost was $463,630 (IQR; 230,795 - 558,533). ICU care was required for 71 (46%) of patients. Overall, 91 (67%) patients developed transplant-related complications, which included infections, sinusoidal obstruction syndrome or graft versus host disease (Table 1). Mortality after HSCT was 22% (n=30) with an increased mortality observed with advanced age at the time of HSCT (Figure 1). The median time to death after the initial HSCT admission was 65 days (IQR; 56-94 days). Conclusion This is a large in-patient cohort of pediatric patients with HLH who underwent HSCT in the US. We observed an improved overall mortality after HSCT in this population compared to previous studies. However, morbidity (particularly from infections) and heath care resource utilization remain high. This stresses the importance of novel therapeutic approaches to improve not only patient survival but also long-term quality of life. Planned future analysis of this database will be aimed at assessing treatment variability; morbidity and mortality by treatment regimen, time to HSCT, and HSCT preparative regimen; and risk factors associated with mortality in pediatric patients with HLH who do and do not undergo HSCT. Disclosures No relevant conflicts of interest to declare.

Positive psychological experiences in allogeneic hematopoietic stem cell transplantation

Positive psychological constructs (e.g., optimism and hope) have been associated with superior health outcomes in the recovery from hematopoietic stem cell transplantation (HSCT) in prior work. However, such studies have not examined a broad range of positive psychological constructs, their sources or evolution over time, or their connections with key health behaviors. We used semistructured qualitative interviews in 25 HSCT patients to explore the nature and sources of positive psychological experiences during the first 100 days after transplantation. Participants completed interviews during their HSCT hospitalization and approximately 100 days after transplantation. Transcribed interviews were organized and analyzed using NVivo 12 software by two coders (κ = 0.92). Interviews focused on the breadth of positive psychological experiences, their sources and evolution during the 100 days, and participants' perceived impact of positive constructs on health behaviors. Several positive psychological constructs especially gratitude, determination, and optimism were frequently expressed. Family support and deliberate participation in pleasant and meaningful activities were the two primary sources of positive psychological experiences after HSCT. At baseline, participants consistently reported gratitude for their donors while follow-up was consistently characterized by hope for cure and return to baseline level of functioning. Additionally, participants related bidirectional relationships between positive psychological well-being experiences and completion of health behaviors over time. As one of the first qualitative studies characterizing the breadth, sources, and evolution of positive psychological experiences in HSCT patients, these findings add to the literature aimed at understanding psychological well-being in this complex and growing patient population.

Strategies for Reducing the Time until Antibiotic Therapy Initiation in Febrile Neutropenia in Hematopoietic Stem Cell Transplantation Hospitalization Unit

Topic Significance & Study Purpose/Background/Rationale Febrile neutropenia (FN) is an oncologic emergency. The time-to-antibiotic administration (TTA) is a quality of care. NF and Sepsis Management Guidelines recommend that the time to onset of the antibiotic therapy be up to 60 minutes, but recent work has shown that the reduction in this period is related to better outcomes. The aim is evaluate the effectiveness of the actions developed to reduce TTA in NF. Methods, Intervention, & Analysis This is a descriptive and retrospective study, performed through the analysis of the TTA indicator in NF and the effectiveness of the actions implemented through the PDCA (Plan / Do / Check / Act) continuous improvement tool, conducted at a Hematopoietic Stem Cell Transplantation (HSCT) Center at a private hospital in Brazil, between January-June 2018. Patients who started antibiotic therapy during neutropenia were eligible for the indicator. The TTA goal is 45 minutes from the recognition of symptoms until time of antibiotic installation. Findings & Interpretation The TTA in the years 2013, 2014 and 2015 were respectively 00:31 (00:08-01:52), 00:31 (00:10-02:00), and 00:33 (00:10-01:58). As of January 2016, the goal was reduced to 00:45, with a result of 00:30 (00:10-01:53). In 2017, there was a worsening of the time to 00:52 (00:06-03:04), coinciding with the implantation of the electronic medical record system in the institution and consequent greater accuracy in the registration of times of symptom onset and antibiotic administration, besides the modification of the methodology for the collection of data. Root cause analysis through the Ishikawa diagram showed opportunities for improvement in shifts transitions and staff training. The established actions were the involvement of the assistance team as multipliers, awareness through training, reduction of the time between shifts through the structured tool IPASS (Illness Severity, Patient Summary, Action list, Situation Awareness and Synthesis by Receiver) and availability the staff to attend this period. The results for January-June 2018 show a 30%-reduction of time: 00:36 (00:10-01:23). Discussion & Implications The involvement of the care team reflected empowerment and greater adherence to TTA. The use of the IPASS tool provided effective and quicker communication in shifts transitions. The awareness of the team was increased. we concluded that the actions implemented were effective, with a reduction of the TTA indicator, between January-June / 2018, with higher quality and safety to the patients submitted to the HSCT.

Effect of Inpatient Palliative Care During Hematopoietic Stem-Cell Transplant on Psychological Distress 6 Months After Transplant: Results of a Randomized Clinical Trial.

Purpose Inpatient palliative care integrated with transplant care improves patients' quality of life (QOL) and symptom burden during hematopoietic stem-cell transplant (HCT). We assessed patients' mood, post-traumatic stress disorder (PTSD) symptoms, and QOL 6 months post-transplant. Methods We randomly assigned 160 patients with hematologic malignancies who underwent autologous or allogeneic HCT to inpatient palliative care integrated with transplant care (n = 81) or transplant care alone (n = 79). At baseline and 6 months post-transplant, we assessed mood, PTSD symptoms, and QOL with the Hospital Anxiety and Depression Scale and Patient Health Questionnaire, PTSD checklist, and Functional Assessment of Cancer Therapy-Bone Marrow Transplant. To assess symptom burden during HCT, we used the Edmonton Symptom Assessment Scale. We used analysis of covariance while controlling for baseline values to examine intervention effects and conducted causal mediation analyses to examine whether symptom burden or mood during HCT mediated the effect of the intervention on 6-month outcomes. Results We enrolled 160 (86%) of 186 potentially eligible patients between August 2014 and January 2016. At 6 months post-transplant, intervention participants reported lower depression symptoms on the Hospital Anxiety and Depression Scale and Patient Health Questionnaire (adjusted mean difference, -1.21 [95% CI, -2.26 to -0.16; P = .024] and -1.63 [95% CI, -3.08 to -0.19; P = .027], respectively) and lower PTSD symptoms (adjusted mean difference, -4.02; 95% CI, -7.18 to -0.86; P = .013), but no difference in QOL or anxiety. Symptom burden and anxiety during HCT hospitalization partially mediated the effect of the intervention on depression and PTSD at 6 months post-transplant. Conclusion Inpatient palliative care integrated with transplant care leads to improvements in depression and PTSD symptoms at 6 months post-transplant. Reduction in symptom burden and anxiety during HCT partially accounts for the effect of the intervention on these outcomes.