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Quality of life Psychosocial adjustment and quality of life among multiple myeloma patients undergoing evaluation for autologous stem cell transplantation AC Sherman1, S Simonton1, U Latif1, R Spohn1 and G Tricot2 1

Behavioral Medicine, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; and Myeloma Institute for Research and Therapy, Arkansas Cancer Research Center, University of Arkansas for Medical Science, Little Rock, AR, USA 2

Summary: Stem cell transplantation has assumed a prominent place in the treatment of multiple myeloma, but relative to patients with other malignancies there is surprisingly little information about the adjustment difficulties and qualityof-life changes that these patients experience. This study examined psychosocial and functional deficits among myeloma patients assessed at a uniform period during their initial diagnostic evaluation, prior to beginning protocols at a transplant center. Validated self-report measures and clinician rating scales were used to assess 213 patients. Outcomes evaluated included emotional distress (Hospital Anxiety and Depression Scale, Brief Symptom Inventory), depression (Hamilton Depression Rating Scale), physical functioning, pain, and energy (SF-12). A significant proportion of patients experienced compromised psychosocial and physical functioning. Roughly one-third reported clinically elevated levels of distress, anxiety, and depression. In all, 59% scored below age-adjusted norms for daily physical functioning, 58% reported at least moderate levels of pain, and over 80% noted at least moderate fatigue. Clinical and demographic correlates of these outcomes were examined. These findings are among the first to characterize quality-of-life outcomes among myeloma patients in the transplant setting, and indicate that many patients experience considerable supportive care needs even prior to beginning aggressive regimens. Results highlight the importance of early screening. Bone Marrow Transplantation (2004) 33, 955–962. doi:10.1038/sj.bmt.1704465 Published online 22 March 2004 Keywords: peripheral stem cell transplantation; multiple myeloma; psychosocial adjustment; quality of life

Despite notable advances in supportive care, peripheral blood stem cell transplantation (PBSCT) remains a

Correspondence: Dr AC Sherman, Behavioral Medicine, Slot 756, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; E-mail: [email protected] Received 18 June 2003; accepted 02 January 2004 Published online 22 March 2004

demanding treatment process. There has been growing interest in behavioral and functional outcomes for patients receiving PBSCT, and in the past decade the research literature has expanded appreciably. To date, however, there has been very little psychosocial research examining the experience of multiple myeloma patients receiving PBSCT. Multiple myeloma, a systemic disease of plasma cells, comprises 10% of hematological cancers.1,2 Cardinal features of myeloma include elevated monoclonal (M) protein levels, increased plasma cells in the bone marrow, lytic bone lesions or generalized osteoporosis, hypercalcemia, and anemia. Median survival is roughly 3–4 years with conventional chemotherapy, which often includes prednisone and melphalan or other alkylating agents (eg, vincristine, carmustine, melphalan, cyclophosphamide, prednisone).3–5 Relative to standard treatment, intensified chemotherapy supported by single or tandem (ie, two transplants within a 6-month interval) autologous PBSCT has been associated with improved tumor response, eventfree survival, and overall survival.6–9 Thus, high-dose therapy followed by autologous PBSCT has assumed a growing role in treatment10–13 and is now considered a front-line therapy, at least for younger patients.4,6,7,10 The recent addition of thalidomide, Revimid (CC-5013), and Velcade (PS 341) has further extended the treatment options for myeloma patients.4 Notwithstanding these advances, longterm outcomes remain disappointing. Moreover, patients are confronted by a range of challenging treatment-related toxicities, often in conjunction with disease-related anemia, renal insufficiency, lytic bone lesions, or compression fractures. Functional and psychosocial well-being may be markedly depleted, particularly among older individuals who are more typically affected by multiple myeloma. The relative absence of systematic information concerning quality of life (QOL) for these patients throughout the course of treatment makes it more difficult for treatment centers to anticipate and address supportive care needs. Much of the QOL literature involving patients with other types of malignancies has focused on allogeneic as opposed to autologous transplants,14–18 which are less commonly used for myeloma patients. Moreover, in many studies, the time frame for assessment has centered on the intermediate19 or, more typically, the long-term post transplant period,15,16,20–23 with fewer studies examining the critical interval before transplantation. Levels of distress

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and psychosocial morbidity appear to be especially high during this period,18,24,25 which warrants increased attention from investigators to help guide clinical services, inform patients about what to expect, and establish baselines to assess subsequent changes. In the few investigations that have evaluated patients with other malignancies prior to autologous marrow or stem cell transplantation, a significant proportion experienced elevated psychological distress. The percentage exceeding clinical cutoff scores for anxiety on various screening measures ranged from 19 to 55%, while those exceeding cutoffs for depression ranged from 11 to 51%.26–29 Rates of distress have been similarly elevated among more heterogeneous samples of patients assessed prior to receiving either autologous, allogeneic, or matched unrelated donor transplants.30–33 Many patients also appear to experience compromised physical or functional status prior to autologous transplantation, although here too information is limited.28,34,35 Most studies that evaluated patients prior to autologous PBSCT have relied on small sample sizes and, as noted, individuals with multiple myeloma were rarely included, in part due to exclusion of older patients from transplant regimens. Thus, it remains unclear how well these findings would characterize myeloma patients, who experience a distinct disease trajectory. Even outside the transplant setting, there has been limited focus on QOL outcomes among multiple myeloma patients.36–40 QOL data were included within a large clinical trial comparing melphalan–prednisone þ alpha interferon vs melphalan–prednisone alone for newly diagnosed myeloma patients.36,37 Problems with pain, fatigue, physical functioning, and global QOL were relatively common in both groups and generally seemed to improve over the course of treatment, although unfortunately changes over time were not analyzed statistically. In another study of previously untreated myeloma patients who were newly enrolled on chemotherapy protocols, levels of emotional distress were comparable to norms for patients with other types of recently diagnosed cancer.38 Similar to findings in other oncology settings,41 physician ratings consistently under-represented patients’ distress. In a study of myeloma patients evaluated much later in the treatment trajectory, an average of 3 years post-diagnosis, levels of emotional distress appeared relatively low.39 A total of 29% of participants reported moderate-to-severe pain. Not surprisingly, however, in both the Silberfarb et al.38 and Poulos et al.39 studies increased pain was associated with heightened emotional distress. These investigations offer important information about psychosocial outcomes among myeloma patients, but the response rates were low in some of these reports38,39 and none focused on patients in the transplant setting. In our previous pilot work in a transplant center, we found that a notable percentage of myeloma patients demonstrated deficits in multiple spheres of functioning, even prior to beginning aggressive conditioning and transplant regimens.24 Common difficulties included nutritional deficits, fatigue, pain, disrupted physical functioning, and heightened distress. The current study focuses on adjustment and QOL in a separate, much larger sample of multiple myeloma patients evaluated early in the course of Bone Marrow Transplantation

care. These patients received comprehensive psychosocial evaluations as a routine part of their initial 4-day diagnostic work-up. Thus, while participants varied somewhat in time since initial diagnosis and extent of prior treatment, all were assessed prior to beginning protocols for high-dose therapy or other treatments at the Myeloma Institute for Research and Therapy (MIRT) at the University of Arkansas for Medical Sciences (UAMS). Because this center is uniquely focused on multiple myeloma and performs the largest number of transplants for this disease in the world, we had an unusual opportunity to assess a large, homogenous sample of myeloma patients at a similar point in the course of treatment. The current study evaluated levels of anxiety, depression, general distress, and health-related QOL, using validated measures. In addition, we examined medical and demographic correlates of these outcomes. This investigation was intended to clarify the status of patients during a critical period early in care and set the stage for a subsequent longitudinal study.

Patients and Methods Patients Participants included 213 consecutive patients assessed as a routine part of their initial outpatient diagnostic evaluation in the MITR at the UAMS between March 2001 and November 2002. The primary purpose of screening is not to select transplant candidates but rather to identify supportive care needs, facilitate early intervention, and prevent subsequent complications. Inclusion criteria included ability to speak and write English, functional status sufficient to permit outpatient assessment, and absence of delirium. Patients who had previously received PBSCT were excluded (n ¼ 30), as were patients seen only for consultation but not treatment (n ¼ 43), and those with solitary plasmacytomas (n ¼ 17) or hematological disorders other than multiple myeloma. Data from six additional patients were excluded because of extensive missing values. None of the patients who attended the screening interview refused to complete the measures. (Data are unavailable for a small but undetermined number of patients who missed their screening appointment due to emergency hospitalization or lastminute scheduling conflicts.) Sample characteristics are described in Table 1. Most patients were white, married, and had been diagnosed relatively recently (median ¼ 3 months). In addition to demographic and disease variables, Table 1 lists beta 2 microglobulin and lactate dehydrogenase (LDH) levels because of their prognostic significance. Most myeloma patients treated at this facility come from out of state. The great majority of patients in this sample subsequently received PBSCT (78.4%) or are scheduled for transplant (1.5%). A total of 46 (21.6%) patients received other regimens due to severe comorbidity (six patients), inability to collect stem cells (three patients), smoldering disease or favorable response to other regimens (27 patients), patient preference for less aggressive treatment (six), or expiration prior to transplant (one). The study was reviewed and approved by the UAMS Institutional Review Board.

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957 Table 1

Sample characteristics

Characteristic

Number (Percent)

Sex Male Female

128 (60.1) 85 (39.9)

Marital status Single Married Divorced/separated Widowed

7 178 15 13

Ethnicity White

189 (88.7)

African American Other

Characteristic

Median (range)

Age

59 (31–81)

Education (years)

14 (5–23)

(3.3) (83.6) (7.0) (6.1)

Months since initial diagnosis

3 (1–246)

16 (7.5) 8 (3.8)

Stagea Smoldering myeloma I II III Unknown

24 59 18 111 1

b2 m 42.5 mg/l p2.5 mg/l Unknown

102 (54.3) 86 (45.7) 25 (11.7)

LDH 4190 U/l p190 U/l Unknown

75 (38.3) 121 (61.7) 17 (7.2)

to other commonly used instruments, is less confounded by somatic items that may reflect illness rather than psychological morbidity. A number of studies have reported evidence of reliability and validity, including several conducted in bone marrow transplant settings.22,44,45 A total score of X13 was used as the cutoff for clinically meaningful distress, in accord with prior research supporting the sensitivity and specificity of these values in screening for major depression and adjustment disorders among cancer patients.45 On the depression and anxiety subscales, a score of X8 represented caseness.46 In the current sample, coefficient alpha was 0.90 for the total score, 0.83 for the depression subscale, and 0.85 for the anxiety subscale.

(11.3) (27.7) (8.5) (52.1) (0.5)

b2 m, b2 microglobulin; LDH, lactate dehydrogenase. a Patients were staged using the Durie and Salmon64 classification.

Procedure Participants were assessed in a semistructured interview by licensed psychologists, and completed several standardized measures of adjustment and health-related QOL as part of the standard clinical procedures for patients newly enrolled at the treatment center. Measures included the following. SF-12. The SF-1242 is a measure of health-related QOL. The longer instrument from which it was derived, the SF36, has been commonly used among cancer patients and bone marrow transplant recipients.43 The SF-12 provides scores for physical functioning (Physical Composite Summary, PCS) and mental health functioning (Mental Component Summary, MCS). Items concerning pain (1 ¼ not at all, 5 ¼ extremely) and energy (1 ¼ none of the time, 6 ¼ all of the time) were also of special interest. Selected items are reverse-scored so that higher scores on this measure indicate better functioning. The psychometric properties of this instrument have been well established.42 Test-retest reliability estimates were 0.86–0.89 for the PCS and 0.76–0.77 for the MCS in previous research.42 Hospital Anxiety and Depression Scale (HADS). The HADS44 generates scores for anxiety, depression, and total distress. This measure was designed to assess anxiety and depressive symptoms in medical populations, and relative

Brief Symptom Inventory (BSI). The BSI47 is a broader measure of psychological symptomatology that has been employed frequently among oncology patients, including those treated in transplant settings.17 It provides three summary scores and nine symptom scores. In the current study, the Global Severity Index (GSI) was used as a summary measure of distress, in conjunction with the anxiety and depression scales. Coefficient alpha was 0.96 for the GSI, 0.85 for anxiety, and 0.85 for depression. Hamilton Depression Rating Scale-17 (HDRS-17). In contrast to the self-report measures noted above, the HDRS48 was used to generate clinician ratings of depressive symptomatology. The HDRS is one of the most commonly used clinical measures of severity of depressive symptoms.49,50 The 17-item version was used in the current study; scores of 7–17 are indicative of mild depression, 18–24 signifies moderate depression, and X25 denotes severe depression. Coefficient alpha was 0.64. Inter-rater reliability estimates were not obtained. Ratings were derived from 1  112h interviews conducted by doctorallevel psychologists experienced in assessing and treating oncology patients.

Data analyses Descriptive statistics were used to characterize the outcome variables. Where available (HADS, HDRS-17), published cutoff scores were used to examine the proportion of patients demonstrating clinically meaningful levels of symptomatology. On the SF-12, we evaluated the percentage of participants whose scores deviated from ageadjusted population norms by 1 s.d.,42 and on the BSI, we examined the proportion whose scores deviated from gender-adjusted population norms by 1 s.d.47 The percentage of patients reporting at least moderately severe pain (X3 on a 5-point scale) and moderately impaired energy (p3 on a 6-point scale) on the SF-12 were noted as well, although no norms are available for these items. Because of the non-normal distribution of some outcome measures, Spearman correlations were used to assess relationships among outcomes, and between outcomes and continuous demographic or medical variables. Mann–Whitney tests and Kruskal–Wallis one-way analyses of variance were used to examine associations between outcome measures and categorical demographic or medical variables. Multiple regression analyses were employed to explore concurrent Bone Marrow Transplantation

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predictors of emotional adjustment (HADS total score) and physical functioning (SF-12 PCS), respectively, using variables that were significant in univariate analyses. To reduce skewness in these analyses, square root transformations were used for the HADS scores, following Winer.51 Tests were two-tailed; as partial adjustment for multiple comparisons, P-values less than 0.01 were considered significant. Power was sufficient (0.87) to detect moderately small effect sizes (r ¼ 0.25).

Results Symptom burden Descriptive statistics for each outcome measure, and the percentage of patients who exceeded cutoff scores, are summarized in Table 2. The level of symptom burden was relatively high across both psychosocial and physical domains.

Concurrent predictors of outcomes Spearman correlations among demographic, medical, and outcome measures are noted in Table 3. As expected, patients who experienced greater physical symptoms also reported more emotional difficulties. Specifically, poor physical functioning (SF-12 PCS) was significantly correlated with higher scores on the HADS total (Po0.000001), HADS depression (Po0.000001), BSI GSI (Po0.000001), BSI anxiety (Po0.01), and HDRS depression (Po0.001) scales, and marginally correlated with higher HADS anxiety scores (Po0.05). Similarly, greater difficulties with pain (all P’so0.001) or fatigue (all P’so0.0001) were associated with significantly poorer scores on each of the psychosocial measures. With respect to demographic factors, higher education was significantly correlated with better SF-12 PCS (Po0.001), SF-12 energy (Po0.001), and SF-12 pain (Po0.0001) scores, with additional trends for better SF-12 MCS (P ¼ 0.10), HADS total (P ¼ 0.06), HADS depression (Po0.08), HADS anxiety (P ¼ 0.09), and HDRS depression (P ¼ 0.07) scores. Increasing age was

Table 2

associated with poorer SF-12 PCS scores (Po0.01) and marginally greater pain difficulties (P ¼ 0.07). Longer time since diagnosis was correlated with marginally higher clinician ratings of depression (P ¼ 0.052). Mann–Whitney tests indicated a trend for women to score marginally higher on the HADS anxiety (Po0.05), BSI depression (Po0.05), BSI anxiety (Po0.05), and HADS total (P ¼ 0.08) scales, relative to men. Compared with individuals from minority groups, Caucasian patients demonstrated poorer energy (Po0.01) and marginally greater HDRS Depression (Po0.05) scores. And perhaps not surprisingly, patients who were employed (full-time or parttime) reported marginally better SF-12 PCS (Po0.05), lower pain (Po0.05), and lower HDRS depression (P ¼ 0.07) scores than did those who were not working. Kruskal–Wallis analyses of variance indicated that tumor stage was significantly associated with SF-12 PCS (Po0.01) and marginally related to SF-12 pain (Po0.05), SF-12 energy (P ¼ 0.09), and HADS depression (Po0.05) scores. Post hoc analyses revealed that individuals with smoldering myeloma (ie, lowest tumor burden) experienced better physical functioning than those with stage 1 or 3 disease. Similarly, patients with stage 1 or 2 disease reported better physical functioning than those with stage 3 disease (ie, highest tumor burden). Individuals with smoldering disease also demonstrated fewer difficulties with pain, energy, and depression than did those with stage 3 disease. A series of multiple regression analyses was used to examine predictors of the primary outcome measures – the HADS total score and SF-12 PCS score, respectively – using variables that were significant or marginally significant in univariate analyses. Results are displayed in Table 4. HADS total distress scores were regressed on gender, education, and SF-12 PCS scores. Poor day-to-day physical functioning (SF-12 PCS) emerged as the sole significant predictor of emotional distress. Variables that were entered into the model to predict SF-12 PCS scores included age, education, disease stage (coded as smoldering myeloma vs active disease), employment (coded as employed vs not), and the HADS total distress score. (Pain and fatigue were not included among the predictors

Descriptive statistics for outcome measures

Measure

Mean (s.d.)

SF-12 physical functioning SF-12 mental health functioning SF-12 energy SF-12 pain HADS total distress HADS anxiety HADS depression BSI global severity index BSI anxiety BSI depression Hamilton depression

33.25 47.18 2.74 3.14 10.74 5.84 4.90 0.47 0.61 0.48 8.47

(11.91) (11.14) (1.37) (1.41) (7.27) (4.16) (3.84) (0.47) (0.65) (0.62) (4.54)

Median

Range

% Exceeding clinical cutoffs

32.17 49.28 2.00 3.00 10.00 5.00 4.00 0.34 0.33 0.17 8.00

9.77–63.70 15.04–66.59 1.00–6.00 1.00–5.00 0.00–38.00 0.00–18.00 0.00–20.00 0.00–2.62 0.00–3.17 0.00–3.17 0.00–23.00

59.4 28.3 80.7 57.6 37.1 34.3 23.9 33.0 33.9 34.4 59.6

Higher scores indicate more severe symptoms except for SF-12 scores, where higher scores indicate better status. Percent of patients exceeding cutoff values is adjusted for age for SF-12 scores, and adjusted for gender for BSI scores. HADS, Hospital Anxiety and Depression Scale; BSI, Brief Symptom Inventory; Hamilton depression, Hamilton Depression Rating Scale. N ¼ 212 for SF-12 and BSI scores, and N ¼ 213 for HADS and Hamilton depression scores. Bone Marrow Transplantation

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Spearman correlations among demographic, medical, and outcome measures

Measure 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

2

3 a

Age 0.14 Education Months since diagnosis HADS total distress HADS anxiety HADS depression BSI global distress BSI anxiety BSI depression Hamilton depression SF-12 pain SF-12 energy SF-12 physical functioning SF-12 emotional functioning

4 a

0.16 0.11

5

6

7

8

9

10

0.02 –0.07 0.07 0.05 0.08 0.00 0.07 0.13 0.12 0.12 0.12 0.10 0.03 0.07 0.02 0.04 0.06 0.06 0.05 0.00 0.13 0.92e 0.90e 0.81e 0.75e 0.70e 0.36e e e e e 0.67 0.75 0.78 0.65 0.26c 0.74e 0.59e 0.64e 0.38e 0.81e 0.79e 0.33e 0.70e 0.27d 0.31e

11 0.13 0.27d 0.02 0.42e 0.27d 0.50e 0.42e 0.27d 0.26c 0.26c

12

13

0.09 0.24c 0.02 0.52e 0.36e 0.61e 0.53e 0.40e 0.37d 0.28d 0.53e

14 b

0.19 0.24c 0.10 0.36e 0.17a 0.50e 0.35e 0.18a 0.18b 0.22c 0.75e 0.55e

0.05 0.12 0.02 0.69e 0.66e 0.59e 0.67e 0.64e 0.61e 0.29d 0.30e 0.46e 0.05

Higher scores indicate more severe symptoms except for SF pain, SF energy, SF physical functioning, and SF emotional functioning, where higher scores indicate better status. a P o0.05. b P o 0.01. c P o 0.001. d P o 0.0001. e P o0.00001.

Table 4 Multiple regression analyses predicting primary outcomes from selected variables Outcome measure

Independent variable Measure

b

P-value

DR2

HADS total distressa

Genderb Education SF-12 PCS

0.12 0.06 0.35

0.07 NS 0.00001

0.01 0.02 0.12

SF-12 PCSc

Age Education Tumor staged Employmente HADS total

0.13 0.20 0.29 0.04 0.31

0.07 0.01 0.00001 NS 0.00001

0.04 0.05 0.11 0.00 0.09

a

Model statistics for HADS: F(3,202) ¼ 12.03, R2 ¼ 0.15, Po 0.00001. Coded as 1 (men) and 2 (women). c Model statistics for SF-12 PCS: F(5,199) ¼ 15.75, R2 ¼ 0.28, Po 0.00001. d Coded as 1 (smoldering myeloma) and 2 (stage 1,2,3). e Coded as 1 (employed outside the home) and 2 (not employed). b

in this model because these items are encompassed within the summary PSC score.) Diminished physical functioning (SF-12 PCS) was significantly predicted by lower duration, more advanced disease stage and greater emotional distress (HADS total).

Discussion Little research has focused on QOL among multiple myeloma patients. Current findings suggest that a substantial proportion of patients experience elevated emotional distress and poor physical functioning, even prior to beginning demanding treatment protocols. On psychosocial measures, more than one-third of participants (33–37%) exceeded cutoff scores for general emotional distress. A similar proportion reported clinically elevated levels of anxiety (34%) and a somewhat smaller number reported

significant depressive symptoms (24–34%). Overall, the relative consistency of findings across different measures of similar constructs is reassuring. Not unexpectedly, the proportion of patients deemed at risk for depression was greater when assessed by a clinician rating scale (60% on HDRS, most of these with ‘mild’ depression) rather than by self-report instruments (HADS, BSI). However, the clinician rating scale (HDRS) appeared to be inflated by somatic symptoms that reflect medical illness rather than mood – a problem also noted in previous studies that used this instrument with medically ill or older patients.52,53 Consequently, we view the other measures as providing better estimates of depressive symptoms in this sample. With respect to physical outcomes, 59% of patients scored well below age-adjusted norms for day-to-day physical functioning, 58% reported pain of at least moderate intensity, and over 80% noted at least moderate levels of fatigue. Pain, which stems from lytic bone disease, fractures, or compression on the nervous system, and fatigue, which is associated with anemia and exacerbated by analgesic, sedative, or chemotherapy agents, are among the most distressing features of multiple myeloma. Optimal control of these symptoms (eg, World Health Organization analgesic algorithm for pain,54 epoetin alfa for anemia, etc) may contribute appreciably to enhanced physical and emotional functioning. Most transplant centers include psychosocial screening as a routine part of the process of evaluation and treatment planning. Unfortunately, the results are rarely shared with other centers, making it more difficult to compare findings, establish base rates, and design support services. The current study highlights the considerable emotional and physical symptom burden that multiple myeloma patients confront early in the course of care. These results are notable because these problems remain largely underdiagnosed,41,55,56 and most would be expected to be exacerbated rather than diminished with the beginning of aggressive high-dose therapy and transplant regimens.27,28,33 Bone Marrow Transplantation

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The prevalence rates found in the present investigation are even higher than those that emerged in our earlier pilot study of myeloma patients at a similar point in treatment;24 taken together, these studies demonstrate that early psychosocial screening is feasible in a busy treatment center and that supportive care needs are extensive. On the SF-12, for example, 59% of patients in the current study exceeded cutoffs (1 s.d.) for disrupted physical functioning and 28% exceeded cutoffs for mental health functioning; only approximately 16% of similarly aged individuals in the general US population scored at these levels. Among patients with other types of malignancies, the proportion that exceeded cutoff scores on screening measures of emotional distress varied across studies. For the most part, the levels of distress in the current sample are a bit higher than those reported in investigations that used the same instrument (HADS) to assess patients prior to autologous transplantation,27,29 or in samples that were mixed for type of transplant30–32 (see Table 5). Among the few exceptions, depressive symptoms were more common (30%) in the Wettergren et al.29 study and cases of anxiety were more prevalent (61%) in the Keogh et al.31 study. The results concerning physical functioning are not directly comparable, because different measures were used in previous investigations and the percentage of patients considered at risk for functional impairment was not reported.34,35 A secondary aim of this investigation was to explore selected correlates of psychosocial and physical functioning. Notably, the variables we examined accounted for only a small proportion of the variance in outcomes. Nevertheless, current findings may offer preliminary information for clinicians about which patients may be most vulnerable. Among a number of predictor variables, debilitated dayto-day physical functioning was the most robust correlate of emotional distress, as one might anticipate. Conversely, emotional distress was the strongest concurrent predictor of compromised physical functioning. No causal conclusions are possible from these data, but findings are consistent with previous research indicating that deficits in one sphere of functioning (eg, depression) were associated with difficulties in multiple other areas as well (eg, nutrition, fatigue, pain),24,38 highlighting the cascade of symptoms that some patients experience. This correspondence between emotional and physical symptoms may be less evident later in the course of treatment, however, because

Table 5

different aspects of functioning appear to have divergent trajectories of recovery.28,31,57 In other words, after active treatment, functional deficits may improve at a different rate than emotional distress or other psychosocial concerns (eg, fear of recurrence, financial pressures). Prior studies have offered mixed findings regarding the impact of basic demographic and medical variables on behavioral and functional outcomes. In the current study, these relationships were generally small. Not surprisingly, patients with more advanced disease reported poorer physical functioning than those with less disseminated disease. Older participants experienced poorer physical functioning than their younger counterparts. Gender was a weak but fairly consistent predictor of concurrent emotional distress, as in some previous BMT studies;20,29 women reported marginally greater emotional difficulties than men across most measures in univariate analyses. Whether women actually experienced greater distress or simply were more amenable to reporting it is unclear. Physical symptoms (fatigue, pain, impaired physical functioning) did not differ strongly by gender. Less educated patients reported greater difficulties with physical and, to a lesser extent, emotional symptoms. Again, most of these relationships were modest in magnitude. Other demographic and clinical characteristics (employment status, ethnicity, time since diagnosis, marital status) had less consistent or negligible associations with outcomes. In terms of clinical implications, results suggest the need for better symptom control (eg, fatigue, pain, distress) early in the course of care. Advances in screening and supportive care services (eg, availability of improved analgesics, antidepressants, epoetin, psychological services) should enhance the prospects for success. Findings also suggest that clinicians should be particularly alert to emotional distress among patients with poor physical functioning. In turn, disrupted physical functioning may be most pronounced among patients with greater emotional distress, more advanced disease, less education and, more equivocally, among older patients. Continued research is needed to clarify more robust correlates or moderators of adjustment. Variables that merit further exploration based on prior theoretical and empirical work include personality resources such as optimism58 and perceived control,23,57 contextual factors such as supportive23,57 and negative social interactions,59 and coping responses such as religious activity.60,61

Percent of patients across studies exceeding cut off scores for emotional distress on HADS prior to transplantation

Study

Current study Hjermstad et al27 Sherman et al24 Wettergren et al29 Hjermstad et al27 Jenkins et al30 Keogh et al31 Leigh et al32

HADS total

HADS anxiety

Cutoff Score

%4Cutoff

Cutoff Score

%4Cutoff

Cutoff score

%4Cutoff

13 — 13 — — 13 — —

37 — 31 — — 30 — —

8 8 8 8 8 — ? 10

34 34 28 32 20 — 61 22

8 8 8 8 8 — ? 10

24 11 25 30 2 — 14 8

allo ¼ allogeneic, auto ¼ autologous, ? ¼ data not provided. Bone Marrow Transplantation

HADS depression

N

213 47 61 20 41 40 28 36

Type of transplant

Auto Auto Auto Auto Allo ? Mixed Mixed

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Among the strengths of this investigation were use of validated measures to assess a range of outcomes among a large, homogeneous sample of myeloma patients at a similar point in treatment. Although care was taken to select psychometrically sound instruments, scores on these measures cannot substitute for clinical diagnoses (eg, major depression, adjustment disorders, steroid-induced mood disorder, etc). Another important limitation was the crosssectional design. We perceived a strong practical need for information about symptom burden during the early phase of treatment, but obviously it is important to assess changes in adjustment and QOL throughout the course of care. These longitudinal projects are underway in our center. In addition, although most patients in this study were diagnosed recently (median ¼ 3 months), the impact of previous medical treatment was not evaluated. Most participants were white and had traveled long distances to seek care at a specialized transplant center; it is unclear how our results would generalize to patients at other treatment centers with a less prominent focus on multiple myeloma. African-American individuals with myeloma remain underrepresented in research despite the disproportionate burden of disease they bear. It would be helpful for future investigations to examine other important psychosocial sequelae, such as sexual difficulties, body image, financial concerns, and illness-related benefits or growth.62,63 Finally, as noted, investigators should explore additional, theoretically relevant sources of risk or resilience, aside from basic medical and demographic variables. Results would provide a stronger foundation to develop appropriate interventions. In the interim, it is clear that adjustment and QOL are significantly disrupted for many multiple myeloma patients even prior to beginning aggressive treatment. Early, systematic screening appears to be an important and feasible component of patient care.24,27,28

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