Quality of life and recovery after graft-versus-host disease

doi:10.1016/j.beha.2008.03.002

Best Practice & Research Clinical Haematology

Volume 21, Issue 2, June 2008, Pages 333-341

https://doi.org/10.1016/j.beha.2008.03.002 Get rights and content

Acute and chronic graft versus host disease (GVHD) has a significant impact on short- and long-term morbidity as well as mortality in patients undergoing hematopoietic-cell transplantation (HCT). As a result of the physical as well as emotional aspects of the transplant process and development of GVHD, quality of life (QOL) in transplant survivors can be adversely affected. The strongest association between reduced QOL and impaired functional status following HCT is the presence of chronic GVHD. Chronic GHVD can have a negative impact on an individual's general health and mental health, and can lead to the development of functional impairments and activity limitations. In HCT survivors without chronic GVHD, self-reported QOL tends to be very similar to that in comparison groups by 1–2 years after HCT. In addition, in individuals who have been successfully treated for chronic GVHD, QOL and overall health status are not different from those with no history of chronic GVHD. These findings suggest that effective new therapies for chronic GVHD are essential, as are standardized tools for the assessment of QOL and functional outcomes in HCT survivors with chronic GVHD in order to gain a better understanding of the overall impact of the condition, as well as the effectiveness of new treatments.

Section snippets

Health-related quality of life after HCT

Health-related QOL (HRQL) has been fairly well studied after transplantation, but there have been several limitations to the studies that make definitive conclusions difficult to reach. First, there have been no uniform standardized QOL assessment tools or methods of analysis that have been utilized in most published data. Second, there is heterogeneity in patient populations studied such that some studies include a wide range of ages, some include recipients of both allogeneic as well as

Acute GVHD and QOL

Lee and colleagues⁸ studied the impact of both acute and chronic GVHD on HRQL and found that the trial outcome index (TOI) score obtained from the Functional Assessment of Cancer Therapy (FACT)-BMT survey was a sensitive indicator regarding the impact of GVHD on a patient's perceived QOL. Patients who had acute GHVD had a measurable decline in their QOL over the first 6 months after HCT compared to those with no acute GVHD who had a stable QOL. However, this adverse impact from acute GVHD did

Risk factors for adverse QOL: pediatric studies

Several studies have specifically examined the impact of HCT on QOL in children. These studies have their own limitations, particularly in the validity of parental report of QOL as a surrogate marker in younger children, and variations between studies in the length of follow-up and types of HCT performed.

To address the variance between parental versus self-report of QOL, Nuss and colleagues surveyed the child as well as the mother and father.¹¹ This study utilized the Pediatric Quality of Life

Impact of chronic GVHD

Few studies have specifically examined the overall impact of chronic GVHD on patients after HCT. We have examined this in the Bone Marrow Transplant Survivor Study (BMT-SS), a collaborative effort between the City of Hope Cancer Center and the University of Minnesota that is examining the long-term outcomes of individuals who have survived ≥2 years after undergoing HCT. Participants of the BMT-SS included individuals who received HCT for hematologic and non-hematologic malignancies and other

Functional outcomes

While many studies have focused specifically on issues related to QOL, few have addressed the issue of overall health status and recovery in patients who have had chronic GVHD. Again from the BMT-SS, we have recently reported such an analysis to determine the impact of chronic GVHD on the overall health status of HCT recipients.¹⁷ The outcomes that were addressed in this analysis included six domains of health status that had been previously reported from the Childhood Cancer Survivor Study¹⁸,

Recovery

As seen in many studies, the majority of HCT survivors will be physically able to function well by 1 year post-HCT, but this is impacted by pre-transplant level of physical performance, family relationships, and chronic GVHD.¹⁹ However, it has been demonstrated that recovery continues beyond the first year and return to full-time work or school may still require a longer period of recovery. Most have returned to full-time school or occupations by 2 years.¹⁹

A multidisciplinary approach to the

Considerations for QOL measurement in survivors with GVHD

It has been demonstrated that patients who suffer from chronic GVHD will experience a significant negative impact on QOL and their functional status. Accurately capturing this information will be crucial to the success of future trials of chronic GVHD therapy. As mentioned previously, the use of common assessment tools will aid in the overall understanding of these issues across different studies and patient populations. Recently recommended as ‘consensus tools’ were the Medical Outcomes Study

Conclusions

Chronic GVHD is the leading cause of morbidity and mortality in HCT survivors. Management of patients with cGVHD is complex and requires a multidisciplinary approach to address the physical and psychological consequences of the disease and its treatment. Response to therapy is suboptimal, and there is an urgent need for systematic study of agents to be used as primary therapy and in the salvage setting. Such studies will be possible only if consensus can be reached regarding meaningful grading

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Cited by (48)

Extracorporeal Photopheresis as Graft-versus-Host Disease Prophylaxis: A Randomized Controlled Trial
2023, Transplantation and Cellular Therapy
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole curative option for many patients diagnosed with hematologic malignancies. A major obstacle is graft-versus-host disease (GVHD), causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied treatment for GVHD, owing in part to its favorable safety profile. In contrast, reports on the use of ECP to prevent GVHD are rare, and randomized controlled trials (RCTs) are lacking. We conducted an RCT to assess whether ECP applied post-transplantation could prevent the development of GVHD within the first year of transplantation. We enrolled 157 patients (age 18 to 74 years) with a hematologic malignancy undergoing their first allo-HSCT, randomized as 76 to the intervention group and 81 to the control group. ECP was initiated directly on engraftment and was planned twice weekly for 2 weeks, then once weekly for 4 weeks. GVHD, relapse, and death were analyzed by Cox regression analysis. During the first year, 45 patients in the intervention group and 52 control patients developed GVHD (hazard ratio [HR], .82; 95% confidence interval [CI], .55 to 1.22; P = .32). There were no differences in acute or chronic GVHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GVHD between the intervention group (per-protocol; n = 39 of 76) and the control group (n = 77), 46% versus 68%, respectively (HR, .47; 95% CI, .27 to .80; P = .006). Relapse occurred in 15 patients in the intervention group and in 11 control patients (HR, 1.38; 95% CI, .64 to 3.01; P = .42). GVHD-free relapse-free survival, event-free survival, overall survival, and nonrelapse mortality did not differ significantly between the 2 study groups. There also was no significant difference in immune reconstitution between the 2 groups. This first intention-to-treat RCT investigating ECP as GVHD prophylaxis in allo-HSCT for hematologic malignancy does not support the use of ECP as an adjunct to standard drug-based GVHD prophylaxis.
Coping and Modifiable Psychosocial Factors are Associated with Mood and Quality of Life in Patients with Chronic Graft-versus-Host Disease
2019, Biology of Blood and Marrow Transplantation
Chronic graft-versus-host disease (GVHD) is one of most common complications following allogeneic hematopoietic cell transplantation (HCT) and the most significant contributor to morbidity and nonrelapse mortality. The physical burdens and psychosocial difficulties of these patients have not been described systematically. An exploration into the rates and correlates of mood and quality of life (QOL) in patients with chronic GVHD is necessary to develop a clinically relevant, evidence-based intervention to promote well-being. From July 2015 to July 2017, adult allogeneic HCT survivors with established moderate to severe chronic GVHD (N = 52) enrolled in a prospective, longitudinal study at a tertiary academic center. We examined the rates and correlates of depression and anxiety symptoms (Hospital Anxiety and Depression Scale) and explored whether constructs including coping strategies (Coping Inventory for Stressful Situations), symptom burden (Lee Symptom Assessment Scale), physical functioning (Human Activity Profile), and perceived social support (Medical Outcomes Study Social Support Survey) predicted QOL trajectory over time (Functional Assessment of Cancer Therapy–Bone Marrow Transplant) at the baseline, 3-month, and 6-month follow-up. Analyses adjusted for age, sex, chronic GVHD severity, and time since chronic GVHD diagnosis. At the baseline, 3-month, and 6-month follow-up, 32.7%, 31.1%, and 37.8% of patients reported clinically significant depression symptoms, and 30.8%, 20.0%, and 36.4% reported clinically elevated anxiety symptoms, respectively. Adjusting for covariates, greater use of negative emotion-oriented coping (β = 0.20, P = .002), less use of task-oriented coping (β = –0.10, P = .021), worse physical functioning (β = –0.07, P = .004), and higher symptom burden (β = 0.07, P = .002) were independently associated with depression symptoms at baseline. Greater use of negative emotion-oriented coping (β = 0.28, P < .001) and worse physical functioning (β = –0.05, P = .034) were independently associated with anxiety at baseline. Patients who used more negative emotion-oriented coping (β = –0.58, P = .035), had less task-oriented (β = 0.40, P = .028) and social diversion-oriented coping (β = 0.35, P = .039), and had higher symptom burden (β = –0.30, P = .001), worse physical functioning (β = 0.32, P < .001), and lower perceived social support (β = 6.47, P = .003) at baseline reported poorer QOL over time. The unmet physical and psychosocial needs of patients with chronic GVHD are substantial and warrant investigation into evidence-based interventions that may improve QOL and mood by targeting modifiable psychosocial constructs identified in this study.
Randomized controlled study of ECP with methoxsalen as first-line treatment of patients with moderate to severe cGVHD
2019, Blood Advances
Citation Excerpt :
Reduced QoL is increasingly recognized as an important feature of GVHD and one that requires greater understanding to address the overall impact on patients.11 In observational studies, almost a third of patients, having undergone HSCT, were considered to have poor QoL, and significant differences were typically observed in patients with moderate or severe GVHD.8,12-15 Improvements in QoL have been observed over time in patients following HSCT, but only in those patients without cGVHD.16
The investigation of extracorporeal photopheresis (ECP) plus standard of care (SoC) (SoC+ECP) in chronic graft-versus-host disease (cGVHD) within prospective, randomized clinical studies is limited, despite its frequent clinical use. This phase 1/pilot study was the first randomized, prospective study to investigate ECP use as first-line therapy in cGVHD, based on the 2015 National Institutes of Health (NIH) consensus criteria for diagnosis and response assessment. Adult patients with new-onset (≤3 years of hematopoietic stem cell transplantation) moderate or severe cGVHD were randomized 1:1 to 26 weeks of SoC+ECP vs SoC (corticosteroids and cyclosporine A/tacrolimus) between 2011 and 2015. The primary endpoint was overall response rate (ORR), defined as complete or partial response, at week 28 in the intention-to-treat population (ITT). Other outcomes included quality of life (QoL) measures and safety. Sixty patients were randomized; ITT included 53 patients (SoC+ECP: 29; SoC: 24). Week 28 ORR was 74.1% (SoC+ECP) and 60.9% (SoC). Investigator-assessed ORR was 56.0% (SoC+ECP) and 66.7% (SoC). Patients treated with SoC experienced a decline in QoL over the 28-week study period; QoL remained unchanged in SoC+ECP patients. Most frequent treatment-emergent adverse events (TEAEs) in SoC+ECP patients were hypertension (31.0%), cough (20.7%), dyspnea (17.2%), and fatigue (17.2%). Seventeen patients (SoC+ECP: 8; SoC: 9) experienced 35 serious adverse events (SAEs). No TEAEs or SAEs were considered related to the ECP instrument or methoxsalen. The encouraging short-term results of this study could inform the design of subsequent studies. This trial was registered at www.clinicaltrials.gov as #NCT01380535.
The Association of Performance Status and Disease Severity in Patients With Chronic Graft-vs-Host Disease
2019, Archives of Physical Medicine and Rehabilitation
Determine the relationship between functional status and degree of specific organ involvement, physical performance, and subjective well-being chronic graft-vs-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation.
Observational cohort.
Outpatient clinic.
Adult patients (N=121) with cGVHD with 634 assessments.
Not applicable.
Karnofsky Performance Status (KPS). Skin, fascia/joints, lungs, upper and lower extremity range of motion, liver, eye, mucosal, and gastrointestinal involvement were measured using the National Institutes of Health GVHD scale. Physical performance was assessed with the 2-minute walk test (2MWT) and hand grip strength. Subjective measures were the Patient Health Questionnaire 9 (PHQ-9) and Lee Symptom Burden (LSB) scale.
Myofascial (P<.001) and lung (P=.001) involvement, 2MWT (P<.001), LSB (P<.001), and PHQ-9 (P=.03) had the largest associations with KPS with liver (P=.05) and hand grip strength (P<.001) more modest associations with KPS.
Patients with cGVHD experience multifactorial impairment in function associated with potentially modifiable symptoms physiatrists have the expertise to address to enhance function. More research is needed to determine rehabilitation interventions to mitigate the impact of cGVHD on function.
Vulvovaginal Graft-Versus-Host Disease
2017, Obstetrics and Gynecology Clinics of North America
Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes
2016, Biomaterials
Citation Excerpt :
Elimination of patient leukemic cells, termed graft-versus-leukemia effect (GVL), is based on allo-reactive T lymphocytes present in the donor graft or infused after HSCT (donor lymphocyte infusion, DLI). However, curative GVL of allo-reactive donor lymphocytes correlates with the risk of graft-versus-host disease (GvHD), a frequent, life-threatening adverse event and the major cause of non-relapsed mortality after allo-HSCT [6]. The high risk of GvHD in allogeneic transplantation settings and the occurrence of off-target and/or on-target/off-tumor activities of otherwise tumor-specific T lymphocytes in cancer treatment have underlined the strong need for safety strategies to specifically and conditionally eliminate infused T lymphocytes.
Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector platform for genetic T lymphocyte engineering, which allows cost-effective high-quality vector productions, remains a critical goal. Alpharetroviral self-inactivating vectors (ARV) have several advantages compared to other vector platforms, including a more random genomic integration pattern and reduced likelihood for inducing aberrant splicing of integrated proviruses. We developed an ARV platform for the transduction of primary human T lymphocytes. We demonstrated functional transgene transfer using the clinically relevant herpes-simplex-virus thymidine kinase variant TK.007. Proof-of-concept of alpharetroviral-mediated T-lymphocyte engineering was shown in vitro and in a humanized transplantation model in vivo. Furthermore, we established a stable, human alpharetroviral packaging cell line in which we deleted the entry receptor (SLC1A5) for RD114/TR-pseudotyped ARVs to prevent superinfection and enhance genomic integrity of the packaging cell line and viral particles. We showed that superinfection can be entirely prevented, while maintaining high recombinant virus titers. Taken together, this resulted in an improved production platform representing an economic strategy for translating the promising features of ARVs for therapeutic T-lymphocyte engineering.

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18Quality of life and recovery after graft-versus-host disease

Section snippets

Health-related quality of life after HCT

Acute GVHD and QOL

Risk factors for adverse QOL: pediatric studies

Impact of chronic GVHD

Functional outcomes

Recovery

Considerations for QOL measurement in survivors with GVHD

Conclusions

Blood

Blood

Lancet

Biology of Blood and Marrow Transplantation

Blood

Blood

Biology of Blood and Marrow Transplantation

Social Science & Medicine

Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry

The New England Journal of Medicine

Organ toxicity and quality of life after allogeneic bone marrow transplantation in pediatric patients: a single centre retrospective analysis

Bone Marrow Transplantation

Acute health-related quality of life in children undergoing stem cell transplant: I. Descriptive outcomes

Bone Marrow Transplantation

Quality of life in 244 recipients of allogeneic bone marrow transplantation

British Journal of Haematology

18
Quality of life and recovery after graft-versus-host disease