Abstract
Background:
We previously showed that integrated palliative care for AML patients during intensive chemotherapy led to improvements in QOL and mood. Coping has been shown to mediate palliative care interventions in advanced cancer; the mechanisms by which improvements occur among AML patients remain unexplained.
Methods:
We conducted a secondary analysis of data from a multisite randomized trial of integrated palliative and oncology care (IPC) (n=86) versus usual care (n=74) for hospitalized patients with AML undergoing intensive chemotherapy. IPC patients met with palliative care at least twice weekly during their initial and subsequent hospitalizations. Patients completed the FACT-Leukemia, HADS, and Brief Cope to assess QOL, mood, and coping at baseline and weeks 2, 4, 12, and 24. We used linear regression models to assess the effect of IPC on coping. We used causal mediation regression models to examine whether changes in coping mediated intervention effects on patient-reported outcomes at week 2.
Results:
160 (68.1%) eligible patients were enrolled. Those randomized to IPC reported improvement in approach-oriented coping (p<0.01) and reduction in avoidant coping (p<0.05). These changes in coping mediated the intervention effects on QOL (95%CI 2.14, 13.63), depression (95%CI −2.05, −0.27), and anxiety symptoms (95%CI −1.25, −0.04). Changes in approach-oriented and avoidant coping accounted for 78% of the total palliative care intervention effect on QOL; 66% of the effect on depression; and 35% of the effect on anxiety symptoms.
Conclusion(s):
Palliative care integrated during intensive chemotherapy for AML patients facilitates coping strategy use. Improvement in coping skills accounts for a substantial proportion of the effect from a palliative care intervention on patient-reported outcomes.
Keywords: AML, Palliative Care Intervention, Coping, Quality of Life, Distress
Precis:
In a secondary analysis of integrated palliative and oncology care compared to usual care for patients with AML receiving intensive chemotherapy, patients who received specialty palliative care experienced positive changes in coping that mediated the effect of the palliative care intervention on quality of life and mood symptoms. Findings highlight the need for supportive care interventions to optimize the quality of life of patients with AML receiving induction chemotherapy.
Introduction
Acute myeloid leukemia (AML) is an aggressive and potentially life-threatening disease, characterized by an abrupt onset and an urgent need to initiate treatment. Many patients with AML are treated with “intensive chemotherapy,” a combination of cytotoxic drugs that require a 4–6 week hospitalization due to significant toxicities and potentially life-threatening complications such as bleeding and sepsis.1–5 During hospitalization for intensive chemotherapy, patients with AML often experience difficult physical symptoms, including fevers, fatigue, mucositis, nausea, vomiting, and diarrhea that negatively impact their QOL and physical function.6–11 Psychological symptoms are also quite prominent in these patients, with over one-third experiencing acute stress reactions from the shock of diagnosis and need for an unexpected and urgent hospitalization.12–14 Patients often feel isolated and struggle with the uncertainty of their prognosis, leading to hopelessness, depression, and anxiety.11,13,15 Despite the heavy burden of an AML diagnosis and treatment, there is little empirical guidance on supportive care interventions for improving QOL and reducing psychological distress in patients.
Palliative care clinicians are highly specialized in complex symptom management and thus well-suited to intervene upon many of the challenges that patients with AML face during their intensive chemotherapy hospitalization. Integration of palliative services into standard hematology care has lagged behind other cancer types, with illness-specific, cultural, and system-based barriers contributing to the divide16–19; however, evidence supporting integration of palliative care early after diagnosis is growing. Provision of specialty palliative services has been effective in improving psychological wellbeing and reducing symptom burden for patients with hematologic cancers undergoing hematopoietic stem cell transplantation.20 We recently extended this work by completing a multisite randomized trial of integrated palliative and oncology care (IPC) compared to usual care for patients with AML hospitalized for intensive chemotherapy. Compared to patients in the usual care group reporting worsened symptoms, patients who received IPC reported improvements in QOL and reductions in anxiety and depression symptoms two weeks into their hospitalization, when patients with AML often feel their worst.21
While these results are promising, the mechanisms by which palliative care is associated with these observed benefits are not understood. Identification of key mechanisms of palliative care interventions is crucial for prioritizing intervention targets, maximizing clinical resources, minimizing burden, and enhancing scalability, and thus is an essential step towards defining a sustainable clinical delivery model.22 Among patients with solid tumors, studies show that integrated palliative care may confer benefit through enhancing patients’ efforts to cope with their illness,23–27 but this intervention mechanism has neither been tested among patients with hematologic malignancies nor demonstrated in the inpatient setting. Therefore, in this study, we aimed to: (1) investigate the effect of the IPC intervention on changes in coping among patients with AML, hypothesizing that IPC would favorably affect patient use of effective coping strategies, and (2) explore whether improvements in coping mediate the effect of IPC on patient-reported outcomes, including QOL and mood, during their hospitalization for intensive chemotherapy.
Methods
Procedure
Study procedures have been reported previously.21 From January 2017 to July 2019, we recruited patients from the Massachusetts General Hospital, Duke University Hospital, University of Pennsylvania, and Ohio State University. Patients admitted for newly diagnosed high-risk AML enrolled in a nonblinded randomized clinical trial evaluating IPC compared to usual care. Study staff obtained approval from the treating oncologist and approached eligible patients within 72 hours of treatment initiation. After providing written informed consent, participants completed baseline questionnaires and were then randomized 1:1, stratified by study site and disease status to receive IPC or usual care. All participants, regardless of randomization, completed follow-up surveys at weeks 2, 4, 12, and 24 after enrollment. This study was approved by the Institutional Review Boards at all participating sites.
Participants
Eligible patients were hospitalized adults aged 18 years or older with high-risk AML receiving intensive chemotherapy. We defined high-risk AML as: (1) newly diagnosed patients 60 years or older, (2) patients at any age with an antecedent hematologic disorder or therapy-related disease, or (3) patients diagnosed with relapsed or primary refractory AML. We considered intensive chemotherapy as a combination of anthracycline and cytarabine (the 7+3 regimen) or a modification of this regimen in a clinical trial with additional drugs added or other similar intensive chemotherapy regimens requiring a 3 to 6 week hospitalization. Patients were excluded if they: (1) had a diagnosis of acute promyelocytic leukemia, (2) were receiving non-invasive treatment, (3) were already receiving palliative care, or (4) had a history of psychiatric or comorbid disease that the treating oncologist believed would interfere with providing informed consent and participating in study procedures.
IPC Intervention
Palliative care clinicians trained to deliver IPC met with patients randomized to IPC within 72-hours of study enrollment for their initial consultation and a minimum of twice weekly throughout the intensive chemotherapy hospitalization as well as throughout any subsequent hospitalizations occurring during the 6-month study. Components of IPC have been described previously.12 Palliative care clinicians initially focused on building rapport and assessing palliative care needs. Throughout hospitalization, clinicians focused on addressing patients’ symptoms, enhancing coping, assessing patients’ illness understanding, ascertaining patient goals and expectations, and assisting with treatment decision-making. The clinicians initiated discussions with patients regarding preferences for end-of-life care and introduced the role of hospice services, as appropriate. Palliative care clinicians continued to follow patients longitudinally during subsequent hospitalizations. IPC was primarily an inpatient intervention; however, patients or clinicians could request outpatient palliative care follow-up, as needed.
Usual Care
Patients randomized to usual care received standard leukemia care, with the supportive care measures instituted by the clinical team. They did not meet with palliative care clinicians for this study, but consultation with palliative care was available upon request or at the discretion of their treating clinicians. A total of 6 (8.1%) participants assigned to usual care received a palliative care consultation during the intensive chemotherapy hospitalization, and 24 (32.4%) consulted with palliative care during a subsequent hospitalization.
Study Measures
Sociodemographic Characteristics
Participants reported demographic information, including age, gender, race, ethnicity, marital status, religion, education level, and income on the baseline questionnaire.
Patient-Reported Outcomes
Coping Strategies:
To evaluate patient use of coping strategies, we used select subscales from the Brief Cope, a 28-item questionnaire that assesses patients’ use of 14 methods of coping per a 4-point Likert scale.28 To reduce burden, participants completed 14-items from the Brief Cope comprising 7 coping strategies that we considered to be highly relevant for AML patients undergoing intensive chemotherapy.15 Two higher-order domains of coping can be calculated from these subscales including approach-oriented coping (i.e., acceptance, active coping, positive reframing, and emotional support) and avoidant coping (i.e., behavioral disengagement, denial, and self-blame).23,25,29,30 These scales have been found to be valid and reliable in samples of patients with cancer.30 Higher scores on both scales indicate greater use of those coping methods.
Quality of Life:
To assess QOL, we used the 44-item Functional Assessment of Cancer Therapy-Leukemia scale (FACT-Leukemia).31 Participants completed the FACT-Leukemia at all timepoints and rated their wellbeing in the past week. Responses are summed to yield a total score, with higher scores indicating better QOL.
Depression and Anxiety Symptoms:
Participants completed the 14-item Hospital Anxiety and Depression Scale (HADS) at all timepoints.32 The HADS consists of two 7-item subscales to measure depression and anxiety symptoms. Scores range from 0 to 21, with higher scores indicating worse symptoms.
Statistical Analysis
We performed statistical analysis with STATA 9.3 software (StataCorp, College Station, TX). We considered two-sided P<.05 to be statistically significant. We used descriptive statistics to summarize sociodemographic characteristics. We used linear regression models adjusting for baseline scores to assess the effect of group assignment (IPC versus usual care) on coping (approach and avoidant) at week 2. We used linear mixed effects models with maximum likelihood estimation to assess the effect of group assignment (IPC versus usual care) on change in coping (approach and avoidant) longitudinally from baseline to week 24, adjusting for baseline scores.
We performed multiple mediator analyses to explore whether changes in coping during the intensive chemotherapy hospitalization mediated intervention effects on QOL, depression symptoms, and anxiety symptoms at week 2, when patients are expected to feel their worst. For each outcome, we constructed a parallel multiple mediator model with group assignment (IPC versus usual care) as the independent variable and change in coping (approach and avoidant) from baseline to week 2 as the parallel mediators. We controlled for the baseline values of the outcome of interest in all models. Bootstrapped estimates of the specific indirect effects and the total indirect effect were interpreted with 95% CIs. Any CI that did not contain zero was considered statistically significant. The magnitude of the total indirect effect for each model was interpreted as the amount by which patient-reported outcomes were expected to change indirectly through approach-oriented and avoidant coping for patients assigned to IPC versus usual care.
Results
Of 235 eligible patients, 160 enrolled (68.1%), with 86 patients randomized to IPC and 74 to usual care. Patients were a median age of 64.4 (range 19.7–80.1) years old, and most were White (86.2%), male (60.0%), and married (73.8%). Sociodemographic characteristics are summarized in Table 1. As previously reported, no meaningful or statistically significant differences were found between the IPC and usual care groups.13
Table 1.
Patient characteristics
| Patient Characteristics | Usual Care (N = 74) |
Integrated Palliative and Oncology Care (N = 86) |
|---|---|---|
| Age, median (range) | 65.2 (22.1–80.1) | 63.0 (19.7–77.8) |
|
| ||
| Female sex, n (%) | 27 (36.5%) | 37 (43.0%) |
|
| ||
| Race, n (%) | ||
| White | 63 (85.1%) | 75 (87.2%) |
| Black | 7 (9.5%) | 8 (9.4%) |
| American Indian | 2 (2.7%) | 2 (2.3%) |
| Asian | 2 (2.7%) | 0 |
| Other | 0 | 1 (1.2%) |
|
| ||
| Hispanic, n (%) | 0 (0.0%) | 5 (6.02%) |
|
| ||
| Diagnosis type, n (%) | ||
| Newly diagnosed AML | 50 (67.6%) | 59 (68.6%) |
| Relapsed AML | 16 (21.6%) | 21 (24.4%) |
| Refractory AML | 8 (10.8%) | 6 (7.0%) |
|
| ||
| Relationship Status, n (%) | ||
| Married/ relationship | 53 (71.6%) | 65 (75.6%) |
| Divorced | 11 (14.9%) | 9 (10.5%) |
| Single | 6 (8.1%) | 6 (7.0%) |
| Widowed | 4 (5.4%) | 5 (5.8%) |
| Missing | 0 | 1 (1.2%) |
|
| ||
| Religion, n (%) | ||
| Catholic | 28 (37.8%) | 32 (37.2%) |
| Non-Catholic Christian | 23 (31.1%) | 29 (33.7%) |
| None | 10 (13.5%) | 12 (14.0%) |
| Jewish | 5 (6.8%) | 2 (2.3%) |
| Muslim | 0 | 2 (2.3%) |
| Atheist | 0 | 2 (2.3%) |
| Other | 7 (9.5%) | 6 (7.0%) |
| Missing | 1 (1.3%) | 1 (1.2%) |
|
| ||
| Education, n (%) | ||
| High school | 16 (21.9%) | 26 (30.2%) |
| College | 34 (45.9%) | 38 (44.2%) |
| Post-Graduate | 23 (31.1% | 21 (24.4%) |
| Missing | 1 (1.3%) | 1 (1.2%) |
|
| ||
| Income, n (%) | ||
| < $25,0000 | 13 (17.6%) | 8 (9.3%) |
| $25,000 - $50,0000 | 14 (18.9%) | 18 (20.9%) |
| $50,000 - $100,000 | 20 (27.0%) | 25 (29.1%) |
| $100,000 - $150,000 | 14 (18.9%) | 9 (10.5%) |
| > $150,0000 | 7 (9.5%) | 20 (23.3%) |
| Missing | 6 (8.1%) | 6 (7.0%) |
|
| ||
| Baseline PRO, mean (SD) | ||
| QOL (FACT-Leukemia) | 115.7 (2.93) | 117.8 (24.45) |
| Anxiety Symptoms (HADS-Anxiety) | 6.2 (4.11) | 6.4 (4.55) |
| Depression Symptoms (HADS-Depression) | 5.6 (3.26) | 5.5 (3.90) |
Intervention Effects on Coping Strategies
Linear regression analyses controlling for baseline coping values revealed that those randomized to IPC reported significantly greater use of approach-oriented coping (B=1.85; SE=0.62; p=0.004) and less use of avoidant coping (B=−0.70; SE=0.29; p=0.02) at week 2 as compared to those randomized to usual care. Using linear mixed effects models, we found that patients who received IPC reported significantly greater use of approach-oriented coping strategies from baseline to week 24 as compared to those randomized to usual care (B=−0.39; SE=0.15; p=0.01). The effect of group assignment on change in use of avoidant coping strategies longitudinally was not significant (B=−0.12; SE=0.08; p=0.16; Fig 1).
Figure 1.
Trajectory of the use of coping strategies among patients with acute myeloid leukemia randomized to integrated palliative and oncology care or usual care. (A) Changes in the use of approach-oriented coping strategies during the 24-week study period. (B) Changes in the use of avoidant coping strategies during the 24-week study period. The y-axes depict mean levels of (A) approach-oriented and (B) avoidant coping strategy use.
QOL Effects Mediated Through Change in Coping
Using parallel multiple mediator analysis, we investigated whether changes in coping during hospitalization mediated observed effects of IPC on QOL at week 2 (Fig 2). First, compared with usual care, IPC was associated with significant improvements in QOL at week 2 (B=8.86; SE=4.26; p<0.05), controlling for baseline criterion scores. Second, increases in approach-oriented coping and decreases in avoidant coping from baseline to week 2 were associated with significant improvements in QOL at week 2 (B=2.66; SE=0.48; p<0.001; B=−4.14; SE=1.08; p<0.001, respectively). Finally, with group assignment and both approach-oriented and avoidant coping (parallel mediators) entered in the model, the effect of IPC on QOL at week 2 became non-significant (B=0.93; SE=4.03; p=0.82) indicating a potential mediation effect. Table 2 depicts estimates of indirect effects, SEs, and bootstrapped 95% CIs for the parallel multiple mediator models. The total indirect effect accounted for 78.0% of the total effect of IPC on QOL. Tests of the specific indirect effects for each mediator revealed that changes in approach-oriented coping during hospitalization mediated the effect of group assignment on QOL at week 2 (B=5.13; SE=2.35; p<0.05). In contrast, tests of the specific indirect effect of changes in avoidant coping during hospitalization mediating the effect of group assignments on QOL at week 2 was not significant (B=1.44; SE=1.22; p>0.05).
Figure 2.
Integrated palliative and oncology care intervention effects on quality of life (QOL) mediated by coping strategies.
Table 2.
Parallel Multiple Mediator Model Effects
| Indirect Effects of IPC versus usual care on quality of life | |||
|---|---|---|---|
|
| |||
| Effect | Bootstrapped SE | Bias-Corrected 95% CI | |
|
|
|||
| Indirect Effect: Δ Approach-oriented coping | 5.13* | 2.35 | [1.25, 10.44] |
| Indirect Effect: Δ Avoidant coping | 1.44 | 1.22 | [−0.07, 5.01] |
| Total Indirect Effect | 6.58 * | 2.89 | [2.14, 13.63] |
| 78.0% of the total effect is mediated via approach-oriented and avoidant coping | |||
| Indirect Effects of IPC versus usual care on depression symptoms | |||
|
| |||
| Effect | Bootstrapped SE | Bias-Corrected 95% CI | |
|
|
|||
| Indirect Effect: Δ Approach-oriented coping | −0.88* | 0.37 | [−1.67, −0.26] |
| Indirect Effect: Δ Avoidant coping | −0.20 | 0.19 | [−0.72, 0.01] |
| Total Indirect Effect | −1.08 | 0.45 | [−2.05, −0.27] |
| 66.3% of the Total Effect is mediated via approach-oriented and avoidant coping | |||
| Indirect Effects of IPC versus usual care on anxiety symptoms | |||
|
| |||
| Effect | Bootstrapped SE | Bias-Corrected 95% CI | |
|
|
|||
| Indirect Effect: Δ Approach-oriented coping | −0.37* | 0.23 | [−0.93, −0.01] |
| Indirect Effect: Δ Avoidant coping | −0.14 | 0.16 | [−0.69, 0.04] |
| Total Indirect Effect: | −0.52* | 0.30 | [−1.25, −0.04] |
| 35.0% of the total effect is mediated via approach-oriented and avoidant coping | |||
Note: Δ = change;
p <.05
Depression Effects Mediated Through Change in Coping
First, compared with usual care, IPC was associated with significant improvements in depression symptoms at week 2 (B=−1.52; SE=0.65; p<0.05), controlling for baseline criterion scores. Second, increases in approach-oriented coping and decreases in avoidant coping from baseline to week 2 were associated with significant reductions in depression symptoms at week 2 (B=−0.48; SE=0.07; p<0.001; B=0.62; SE=0.16; p<0.001, respectively). Finally, with group assignment and both approach-oriented and avoidant coping (parallel mediators) entered in the model, the effect of IPC on depression symptoms at week 2 became non-significant (B=−0.55; SE=0.59; p=0.36) indicating a potential mediation effect (Fig 3). The total indirect effect accounted for 66.3% of the total effect of IPC on depression symptoms. Tests of the specific indirect effects for each mediator revealed that changes in approach-oriented coping during hospitalization mediated the effect of group assignment on depression symptoms at week 2 (B=−0.88; SE=0.37; p<0.05). In contrast, tests of the specific indirect effect of changes in avoidant coping during hospitalization mediating the effect of group assignments on depression symptoms at week 2 was not significant (B=−0.20; SE=0.19; p>0.05; Table 2).
Figure 3.
Integrated palliative and oncology care intervention effects on depression symptoms mediated by coping strategies.
Anxiety Effects Mediated Through Change in Coping
First, compared with usual care, IPC was associated with significant improvements in anxiety symptoms at week 2 (B=−1.41; SE=0.59; p<0.05), controlling for baseline criterion scores. Second, increases in approach-oriented coping and decreases in avoidant coping from baseline to week 2 were associated with significant reductions in anxiety symptoms at week 2 (B=−0.24; SE=0.07; p<0.01; B=0.48; SE=0.15; p<0.01, respectively). Finally, with group assignment and both approach-oriented and avoidant coping (parallel mediators) entered in the model, the effect of IPC on anxiety symptoms at week 2 became non-significant (B=−0.96; SE=0.59; p=0.11) indicating a potential mediation effect (Fig 4). The total indirect effect accounted for 35.0% of the total effect of IPC on anxiety symptoms. Tests of the specific indirect effects for each mediator revealed that changes in approach-oriented coping during hospitalization mediated the effect of group assignment on anxiety symptoms at week 2 (B=−0.37; SE=0.23; p<0.05). In contrast, tests of the specific indirect effect of changes in avoidant coping during hospitalization mediating the effect of group assignments on anxiety symptoms at week 2 was not significant (B=−0.14; SE=0.16; p>0.05; Table 2).
Figure 4.
Integrated palliative and oncology care intervention effects on anxiety symptoms mediated by coping strategies.
Discussion
In this examination of integrated palliative and oncology care compared to usual care for patients with AML receiving intensive chemotherapy, we found that IPC facilitated greater use of approach-oriented and avoidant coping strategies. Moreover, these changes in coping were associated with improvements in QOL and reductions in depression and anxiety symptoms at week 2, when patients are expected to feel their worst. Findings from this secondary analysis extend evidence supporting the focus on coping as a central component of palliative care interventions and the beneficial effect of this factor on patient-reported QOL and mood for those diagnosed with AML receiving intensive chemotherapy.
Integration of specialty palliative care services in the present study impacted patient use of coping strategies. Whereas approach-oriented coping strategies (i.e., acceptance, active coping, positive reframing, and emotional support) directly address or manage the impact of stress on patients, avoidant coping strategies (i.e., behavioral disengagement, denial, and self-blame) involve withdrawing from stress. IPC impacted use of both of these forms of coping. These benefits occurred within a two-week timeframe and at a time when patients with AML have a high burden of toxicity and physical symptoms. The ability of IPC to facilitate patient use of coping strategies in such a short time span and during the intensive treatment period suggests that increasing availability of supportive care services, particularly palliative care, during hospitalization may be an important way we can support our patients with AML in better coping with the challenges they face during their hospital stay. Moreover, participation in IPC during hospitalization led to sustained use of approach-oriented coping strategies throughout the next six months, suggesting that patients who work with palliative care are likely to maintain these coping gains well beyond their inpatient experience. In contrast, use of avoidant coping strategies investigated longitudinally did not change over the six month study. The lack of longitudinal change may be due to the already low mean levels of reported avoidant coping strategy use in this study or perhaps may be partially reflective of the inpatient nature of the intervention that largely did not provide support outside of that environment. It will be important for future research in this area to take this question into consideration as we do not have the necessary data to definitively explain this pattern.
Identification of mechanisms responsible for conferring benefit within successful palliative care intervention trials is instrumental for developing focused interventions that are effective, economical, and scalable as well as optimized for implementation into clinical practice. Based on compelling evidence from prior work examining coping among patients with solid tumors,23,25–27 our analysis focused on examination of facets of coping as the therapeutic mechanism of action. In the present study, we found that specialty palliative care services provided during the intensive chemotherapy hospital stay for AML patients led to reduced depression and anxiety symptoms and improved QOL through enhanced coping capabilities. These effects were principally mediated through the approach-oriented coping pathway. Greer and colleagues found that an early integrated oncology and palliative care intervention led to positive changes in approach-oriented but not avoidant coping and that these changes resulted in improved QOL and reduced depression symptoms for patients with incurable lung or GI cancer.23 Thus, findings from the present study extend this evidence to a hematologic cancer population and suggest that facilitation of coping efforts, particularly approach-oriented coping--including problem-solving, positive reinterpretation, acceptance, and emotional support--is a key mechanism of action of early integrated palliative care interventions and an important target for improving QOL and mood for patients with AML.
The total indirect effects of coping on QOL and depression were robust, accounting for 78% and 66% of the total effect of IPC on QOL and depression symptoms, respectively. The magnitude of these effects provides further support for the focus on enhancing coping as a key mechanism of action in the efficacy of palliative care interventions for improving QOL and depressive mood. In contrast, coping only accounted for 35% of the variance in reducing anxiety symptoms for patients receiving IPC. Coping is a complex construct, and this smaller magnitude may be due to facets of coping that were not measured in this study. It is also possible that integrated palliative care acts on other mechanisms (e.g., symptom management) that are more directly linked to patient-reported anxiety. Exploration of other mechanisms that may contribute to observed reductions in anxiety is an important avenue for future research.
Our study has several noteworthy limitations. First, the intervention was carried out by specialized palliative care clinicians at tertiary cancer centers with a homogenous group of patients, and findings may not generalize to other settings or to diverse or less affluent patient groups. Second, nearly one third of patients assigned to usual care consulted with palliative care at some point during the study; thus, findings may be an underestimate of the beneficial impact that palliative care services have on coping. Moreover, patients were not prohibited from obtaining psychosocial care which may also facilitate adaptive coping efforts; this represents a possible confounder not measured in the present study. In addition, there is no accepted criterion score on the Brief COPE representing clinically-signficant use of coping strategies, and we are unable to comment on the clinical significance of coping strategy use in this study. Finally, the study design and overlap in timing of assessments limit our ability to determine direction of effects and declare statistical or clinical causality between coping and patient-reported outcomes.
This work demonstrates that involvement of palliative care for patients with AML undergoing intensive chemotherapy led to improvements in approach-oriented coping within the first two weeks of the intervention that were ultimately sustained throughout the study. Furthermore, these positive changes in coping mediated the beneficial effects on QOL and mood at a time when patients are experiencing a high burden of physical symptoms and emotional distress. The identification of coping as a key mediator in this study suggests that psychosocial interventions aimed at facilitating adaptive coping may broadly be helpful, and referral to these resources may be an important way the oncology team can support their patients with AML. This work advances the science of palliative care by identifying the impact of specialty palliative care services on patient use of coping strategies and elucidating a potential mechanism of benefit with AML patients. Thus, findings fit within a larger literature beginning to define active components of palliative care interventions.
Acknowledgments:
We thank the patients for their participation in this study.
Funding: This work was supported by the MGH ECOR (Temel) and the Leukemia and Lymphoma Society (Dr. El-Jawahri is a Scholar in Clinical Research of the Leukemia and Lymphoma Society). This was also supported by T32 CA092203 (Dr. Nelson).
Footnotes
Conflict of Interests: JG receives royalties from Springer Humana Press and has research funding from Gaido Health/BCG Digital Ventures. TWL reports the following disclosures from the past 24 months: personal fees for consulting or advisory boards from AbbVie, Agios, AstraZeneca, Amgen, Astellas, CareVive, BMS/Celgene, Daiichi-Sankyo, Heron, Flatiron, Otsuka, Pfizer, and Seattle Genetics; royalties from UpToDate; speakers bureau fees from Agios, AbbVie, and BMS/Celgene; grants and/or research contracts from the American Cancer Society, AstraZeneca, BMS, Jazz Pharmaceuticals, the NINR / NIH, and Seattle Genetics. Other authors have no disclosures.
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