Biology of Blood and Marrow Transplantation
Volume 15, Issue 1, Supplement , Pages 29-32, January 2009

Psychosocial Sequelae of Hematopoietic Cell Transplantation in Survivors and Caregivers

  • Michelle M. Bishop

      Affiliations

    • Corresponding Author InformationCorrespondence and reprint requests: Michelle M. Bishop, PhD, Department of Medicine, University of Florida, Box 100277, Gainesville, FL 32610-0277.

Department of Medicine,University of Florida, Gainesville, Florida

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Introduction 

Numerous cross-sectional and some longitudinal studies have described the health-related quality of life and psychosocial sequelae of survivors after hematopoietic cell transplantation (HCT). The majority of HCT survivors seem to do well with regard to their overall physical, psychologic, social, and spiritual well-being. However, psychosocial recovery can take longer than physical recovery, and for many, significant residual difficulties remain, including fatigue, distress, sexual problems, and cognitive difficulties. Family caregivers also can experience long-lasting adverse effects from the transplant and caregiving experiences. This brief review will focus primarily on studies of long-term survivors and caregivers (at least 1 year post-HCT) conducted in the last decade (see Mosher et al. [1] for a detailed review of these issues). Although there are no data on the effectiveness of psychosocial interventions in long-term HCT survivors, interventions effective with survivors in the peritransplant period and with non-HCT cancer survivors will be noted, along with suggestions for the future.

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Fatigue 

One of the most frequently reported symptoms of HCT survivors is fatigue. A subjective sense of physical, emotional, and/or cognitive exhaustion that is disproportional to recent activity and interferes with functioning, fatigue does not appear to resolve with time [2]. Approximately one-third of autologous and allogeneic 2-year survivors reported being bothered “a lot” or “extremely” by fatigue [2]. Fatigue levels have exceeded population norms in long-term survivors at 3-5 years [3] and matched controls a mean of 7 years post-HCT (range 2-23 years) [4]. At least 1 study found that autologous HCT survivors reported more fatigue than allogeneic HCT recipients after 3 years [3]. Although the specific cause of persistent fatigue is unknown, a number of physiologic, biochemical, and psychologic mechanisms have been postulated. Several randomized trials provide evidence of the effectiveness of exercise interventions to reduce fatigue and medical complications, and improve physical performance and quality of life, with no reported negative effects (see review [5]). Other studies have found energy improvement with administration of erythropoietin and cognitive-behavior therapy that included relaxation training. However, all these studies have been conducted in the peritransplant setting, and need to be replicated with long-term survivors. Clinical practice guidelines for fatigue are available from the National Comprehensive Cancer Network (NCCN; www.NCCN.org), which recommend use of a single-item screening question and provide a treatment decision tree.

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Distress, Depression, Anxiety, and Posttraumatic Stress Disorder (PTSD) 

Distress, suggested by some as “the sixth vital sign,” is ubiquitous among HCT survivors. Distress includes the continuum of subclinical feelings of vulnerability, sadness, and fear to clinically significant depression, anxiety, and PTSD. Almost all survivors report fear of recurrence, regardless of the number of years since transplant. Financial concerns also are common in both autologous and allogeneic HCT survivors [2] and 10-year survivors were more likely than matched controls to have experienced denial of life and health insurance [6]. Other significant concerns of survivors are noted in Table 1.

Table 1. Sources of Distress for HCT Survivors
Physical Problems/Medical ConcernsPsychologic ProblemsSocial and Community Reintegration ProblemsSpiritual/Existential Concerns
•Fatigue/stamina•Fear of recurrence•Return to former roles (parenting, spousal, work, community)•Spiritual crisis (loss of faith, feeling of being punished or forsaken)
•Continued health problems (eg, GVHD, joint, skin, lung problems)•Uncertainty of future for self and family•Resumption of social relations•Loss of hope
•Late effects•Disrupted life plans related to education, job/career, retirement•Relationship/marital problems•Loss of life purpose or meaning in life
•Cognitive difficulties•Guilt (survivor guilt, family burden)•Employment and insurance discrimination•Disappointment or disconnection with former religious/spiritual community
•Sleep difficulties•Diminished self-worth (“damaged” by treatment, dependent on others)•Financial insecurity (treatment-related expenses, debt, reduced earning ability)
•Sexual dysfunction and/or infertility•Wondering if they will “return to normal”
•Appearance changes
•Appetite problems

HSCT indicates hematopoietic stem cell transplantation; GVHD, graft-versus-host disease.

Clinically significant depressive symptoms have been reported in 9%-35% of long-term HCT survivors 2, 4, 7, levels higher than in matched controls [4]. Others have not found elevations of depression in long-term survivors 3, 6, but have found elevations in anxiety in 18% of 10-year survivors, compared to 10% in matched controls [6]. PTSD also has been a significant concern for some 5%-19% of adult survivors of HCT [1].

Better pretransplant psychologic functioning, better posttransplant physical and sexual functioning, and less fatigue are all associated with less distress. Having chronic graft-versus-host disease (cGVHD) and low social support has been associated with depression in survivors. Associations between distress or depression and demographic and medical variables have been mixed. Distress has been associated with medication nonadherence [7], and depression was found to be an independent predictor of death (threefold greater risk) in the first 12 months after HCT, adjusting for other prognostic factors [8]. These findings underscore the need for regular assessment of distress (shown to be feasible [7]), followed by appropriate treatment. Commonly used self-report measures of depression or anxiety may not fully capture the fears and concerns of HCT survivors; thus, specific measures of cancer-related distress should be considered. Clinical practice guidelines from the NCCN are available for distress, as well, (www.NCCN.org), which recommend use of the Distress Thermometer, a 1-item screening measure, validated in HCT patients. Although there are few studies of psychologic interventions with HCT survivors, there exists a large, applicable, evidence-base for effective psychosocial interventions with cancer patients (see meta-analysis of randomized trials [9]).

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Sexual Problems 

Sexual problems are frequently reported by survivors [2], with 1 study documenting 80% of female and 46% of male allogeneic HCT survivors reporting sexual problems 5 years post-HCT [10]. Despite prevalence of sexual problems, only half of patients, in 1 study, reported discussion of sexuality with their health care provider [11]. Sexual problems can manifest as lower rates of sexual activity, satisfaction, response, and performance. Often caused by physiologic changes secondary to disease or treatment (eg, ovarian failure, cGVHD-related vaginal stenosis or mucosal changes, gonadal or cavernosal arterial insufficiency), sexual dysfunction also can involve a complex interaction between physical, psychosocial, and relational issues. Several hormonal and mechanical interventions have been described for sexual difficulties, although no treatments have been tested in females in randomized trials. There is some evidence that brief counseling, as well as education that focuses on couples communication and gradually increasing and relearning pleasurable and intimate behaviors, are helpful.

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Cognitive Difficulties 

Survivors frequently complain of cognitive difficulties after HCT, and evidence of impairment on objective tests have been noted in 60% of adult HCT survivors at least 2 years after transplant [12]. A range of cognitive functions may be affected, including attention, concentration learning, memory, processing speed, executive function, and fine motor control. Few specific risk factors of HCT have been identified; however, both HCT and GVHD treatments may play a role, along with health difficulties, fatigue, and mood. There currently are no good instruments to screen for cognitive difficulties, although one is being developed (http://www.facit.org/qview/qlist.aspx). Referral to a neuropsychologist for further evaluation and rehabilitation is recommended if significant cognitive difficulties interfere with functioning. Treatment may include compensatory strategy training, cognitive rehabilitation, pharmacotherapy (ie, psychostimulants, antidepressants, or anxiolytics), or cognitive-behavioral psychotherapy.

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Positive Changes 

The majority of HCT survivors report experiencing positive changes post-HCT [4], as well. These include greater inner strength and appreciation for life, closer interpersonal relationships, reprioritizing “what really matters,” renewed faith, and sense of gratitude. The ability to find meaning in the experience may help to buffer some of the adverse psychosocial affects of HCT.

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The Impact of Hct on Family Caregivers 

Although family caregivers are critical to the recovery and well-being, and even survival [13], of HCT survivors, little attention has been paid to the impact of HCT on their physical and psychosocial well-being. Spouse caregivers can experience higher levels of anxiety and depression than survivors in the peritransplant period, and distress levels similar to that of survivors in the years to follow [14], as well as fatigue, sexual difficulties, and sleep problems [14]. They also may suffer from a greater sense of isolation and limited social support than survivors, and experience fewer positives [14]. Caregiver well-being should be monitored, and they may need permission to seek help and support for themselves, as well as help understanding that if they do not take care of themselves they will not be able to provide the quality or length of care for the survivor that they desire.

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Addressing Psychosocial Sequelae: Why Is It Important and What Can We Do? 

Psychosocial issues, such as elevated distress and depression, can predict adherence [7], slower or poorer return of function, and even survival rates [8]. Early identification and referral for psychosocial problems can result in better satisfaction with care, improved patient-doctor communication, fewer complications, and improved outcomes. The recent Institute of Medicine report, Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs, states high-quality care is not possible without addressing patients' psychosocial health needs, which must become standard care. Patient education, support, assessment and treatment are critical elements to addressing psychosocial concerns of survivors and their caregivers.

To be most effective, patient assessment and education should take place throughout the HCT process, from pretransplant evaluations, to determine patient and family strengths and devise individualized, multidisciplinary treatment plans (eg, see Bryant et al [15]), through continued surveillance of both medical and psychosocial issues during survivorship. Development of treatment summaries and survivorship care plans that include psychosocial issues is a first step. Patient- and caregiver-focused educational materials and support services are available through advocacy groups such as BMT Info Net, nbmtLINK, and the NMDP. Further development of survivorship-specific materials and resources for support and intervention is critical, as is standardization of delivery of psychosocial care by educating heath care providers, empowering patients and families, and providing access to a central source of information for both.

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Acknowledgments 

Financial disclosure: The author has nothing to disclose.

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References 

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 Financial disclosure: See Acknowledgments on page 31.

PII: S1083-8791(08)00422-9

doi:10.1016/j.bbmt.2008.10.001

Biology of Blood and Marrow Transplantation
Volume 15, Issue 1, Supplement , Pages 29-32, January 2009

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