Ashley M. Nelson

Sleep Disruption in Hematopoietic Cell Transplantation Recipients: Prevalence, Severity, and Clinical Management

Sleep disruption is common among hematopoietic cell transplant (HCT) recipients, with over 50% of recipients experiencing sleep disruption pre-transplant, with up to 82% of patients experiencing moderate to severe sleep disruption during hospitalization for transplant and up to 43% after transplant. These rates of sleep disruption are substantially higher than what we see in the general population. Although sleep disruption can be distressing to patients and contribute to diminished quality of life, it is rarely discussed during clinical visits. The goal of the current review is to draw attention to sleep disruption and disorders (ie, insomnia, obstructive sleep apnea, restless legs syndrome) as a clinical problem in HCT in order to facilitate patient education, intervention, and research. We identified 35 observational studies published in the past decade that examined sleep disruption or disorders in HCT. Most studies utilized a single item measure of sleep, had small sample size, and included heterogeneous samples of patients. Six studies of the effects of psychosocial and exercise interventions on sleep in HCT have reported no significant improvements. These results highlight the need for rigorous observational and interventional studies of sleep disruption and disorders in HCT recipients..

Sleep quality following hematopoietic stem cell transplantation: longitudinal trajectories and biobehavioral correlates

The present study examined changes in sleep quality following hematopoietic stem cell transplantation (HSCT) and investigated associations with biobehavioral factors. Individuals undergoing HSCT for hematologic malignancies (N=228) completed measures of sleep quality and psychological symptoms pre-transplant and 1, 3, 6 and 12 months post transplant. Circulating inflammatory cytokines (IL-6, TNF-α) were also assessed. Sleep quality was poorest at 1 month post transplant, improving and remaining relatively stable after 3 months post transplant. However, approximately half of participants continued to experience significant sleep disturbance at 6 and 12 months post transplant. Mixed-effects linear regression models indicated that depression and anxiety were associated with poorer sleep quality, while psychological well-being was associated with better sleep. Higher circulating levels of IL-6 were also linked with poorer sleep. Subject-level fixed effects models demonstrated that among individual participants, changes in depression, anxiety and psychological well-being were associated with corresponding changes in sleep after covarying for the effects of time since transplant. Sleep disturbance was most severe when depression and anxiety were greatest and psychological well-being was lowest. Findings indicate that sleep disturbance is a persistent problem during the year following HSCT. Patients experiencing depression or anxiety and those with elevated inflammation may be at particular risk for poor sleep.

Spirituality and the recovery of quality of life following hematopoietic stem cell transplantation.

OBJECTIVE Spirituality has been linked to improved adjustment and functioning in individuals with cancer; however, its effect on quality of life following hematopoietic stem cell transplantation (HSCT) has not been well-studied. This study investigated changes in spirituality in hematologic cancer patients recovering from HSCT and relationships between spirituality and dimensions of quality of life following HSCT. METHODS Participants (N = 220) completed measures of two dimensions of spirituality (meaning/peace and religious faith), depression, anxiety, fatigue, pain, and physical and functional well-being prior to transplant and at 1-, 3-, 6-, and 12-months posttransplant. RESULTS Meaning/peace declined at 1-month posttransplant and returned to pretransplant levels by 6-months posttransplant, and faith increased from pretransplant to 6-months posttransplant. Mixed-effects linear regression models indicated that greater pretransplant meaning/peace, but not religious faith, predicted less depression, anxiety, and fatigue, and better physical and functional well-being during the 12-months following transplant. CONCLUSIONS The capacity to find meaning and peace may facilitate recovery following HSCT. Results suggest that spirituality may be a resilience factor that could be targeted to improve quality of life for HSCT recipients.

Effect of Androgen Deprivation Therapy on Sexual Function and Bother in Men with Prostate Cancer: A Controlled Comparison

The adverse sexual effects of androgen deprivation therapy (ADT) on men with prostate cancer have been well described. Less well known is the relative degree of sexual dysfunction and bother associated with ADT compared to other primary treatment modalities such as radical prostatectomy. We sought to describe the trajectory and relative magnitude of changes in sexual function and bother in men on ADT and to examine demographic and clinical predictors of ADTs adverse sexual effects.

The Role of Age in Neurocognitive Functioning among Adult Allogeneic Hematopoietic Cell Transplant Recipients

Improvements in supportive care have enabled allogeneic hematopoietic cell transplantation (HCT) to be performed in increasingly older patients. HCT is associated with neurocognitive impairment, which may be exacerbated in older adults due to normal neurocognitive decline associated with aging. The goal of this study was to evaluate whether increasing age of allogeneic HCT recipients is associated with worse neurocognitive outcomes over time relative to a matched sample of individuals without cancer. Patients (n = 140; 42% female; M age, 51 years; range, 20 to 76 years; 31% with acute myelogenous leukemia) completed neurocognitive assessments before transplantation and 3 months and 1 year after transplantation. Controls (n = 75; 56% female; M age, 53 years; range, 21 to 74 years) completed assessments at comparable time intervals. Linear mixed models revealed that regardless of age, patients demonstrated worse performance than controls before transplantation in verbal memory, visual memory, and total neuropsychological performance, and over time in executive functioning. In addition, older age was associated with worse performance in verbal memory (P = .02) and verbal fluency (P = .05) over time in patients compared with controls. Specifically, older (65+ years) patients had worse verbal memory and verbal fluency than older and younger (<65 years) controls post-transplantation (Cohens d = .22 to .39). These data indicate that age may be a risk factor for worse neurocognitive outcomes after allogeneic HCT. If replicated, our results suggest that older candidates for allogeneic HCT should be counseled regarding the risk of cognitive problems after transplantation.

Quality of life after pelvic exenteration for gynecologic cancer: Findings from a qualitative study.

Pelvic exenteration (PE) in carefully selected gynecologic cancer patients has a 5‐year survival rate as high as 60%. Thus, there is a growing number of PE survivors dealing with the effects of this radical surgery. The current study sought to explore womens physical, psychological, and social quality of life (QOL) after PE.

A phase I clinical trial of ruxolitinib in combination with nilotinib in chronic myeloid leukemia patients with molecular evidence of disease

PURPOSE Preclinical evidence indicates that the bone marrow microenvironment provides a protective niche for leukemic stem cells, allowing them to evade the effects of BCR-ABL tyrosine kinase inhibitors (TKIs), but that targeting of the JAK-STAT pathway with the JAK2 inhibitor ruxolitinib increases TKI-induced apoptosis. A phase I clinical trial (NCT01702064) investigated the tolerability and safety of treating chronic-phase chronic myeloid leukemia patients with ruxolitinib in combination with the BCR-ABL TKI nilotinib and explored initial efficacy evidence. EXPERIMENTAL DESIGN Eleven patients already treated with single-agent nilotinib (300-400 mg twice daily) commenced combination therapy, and molecular responses were evaluated after 6 months. Three ruxolitinib dose cohorts were studied: 5 mg, 10 mg, and 15 mg twice daily. RESULTS One patient experienced a grade 3/4 adverse event (hypophosphatemia) and 36% of patients experienced grade 1/2 anemia. Of 10 patients who were evaluable for responses, 40% had undetectable BCR-ABL transcripts, as measured by quantitative RT-PCR after 6 months. Plasma inhibitory assay results revealed a decrease in phospho-STAT3 levels after treatment with ruxolitinib. The recommended phase 2 dose of ruxolitinib was 15 mg BID. CONCLUSIONS Overall, this combination was safe and well-tolerated, and the molecular responses were encouraging, thereby warranting further investigation in a phase 2 trial.

Sleep disruption among cancer patients following autologous hematopoietic cell transplantation

Despite a high prevalence of sleep disruption among hematopoietic cell transplant (HCT) recipients, relatively little research has investigated its relationships with modifiable cognitive or behavioral factors or used actigraphy to characterize sleep disruption in this population. Autologous HCT recipients who were 6–18 months post transplant completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors upon enrollment. Patients then wore an actigraph for 7 days and completed a self-report measure of sleep disruption on day 7 of the study. Among the 84 participants (age M = 60, 45% female), 41% reported clinically relevant sleep disruption. Examination of actigraph data confirmed that, on average, sleep was disrupted (wake after sleep onset M = 66 min) and sleep efficiency was less than recommended (sleep efficiency M = 78%). Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors were related to self-reported sleep disruption (p values<0.05) but not objective sleep indices. Results suggest that many HCT recipients experience sleep disruption after transplant. Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and maladaptive sleep behaviors are related to self-reported sleep disruption and should be considered targets for cognitive behavioral intervention in this population.