A Prospective Study of Psychosocial Morbidity in Adult Bone Marrow Transplant Recipients

A Prospective Study of Psychosocial Morbidity in Adult Bone Marrow Transplant Recipients PETER

L.

JENKINS, MRCPSYCH., HELEN LESTER, MBBS

JULIE ALEXANDER, MBBS, JACK WHITTAKER, MRCP

Forty recipients of bone marrow transplantation were recruited prospectively and assessed pretransplant, at I month postdischarge, and at 6 months postdischarge between 1989 and 1990. Assessments included a ps.vchiatric inten'iew, a variety of standardized questionnaires (Hospital Anxiety and Depression Scale, Mental Attitude to Cancer Scale, Psychosocial Adjustment to Illness Scale), and a standardized diagnostic interview. The influence offactors such as depression and anxiety upon length of stay, survival, psychosocial adjustment, and negative prognostic attitudes were examined. 1n contrast to other studies, little influence was found for psychiatric illness on physical outcome variables. but they did affect psychosocial outcome. The implications of these findings are discussed. (Psychosomatics 1994; 35:361-367)

B

one marrow transplantation (BMT) is a treatment that is becoming more frequent. Allogeneic transplantation from related donors and autologous transplantation from the recipients' own marrow have both been shown to be effective treatments for a variety of conditions, including acute and chronic leukemias, severe combined immunodeficiencies, lymphoma, and aplastic anemia. I Increasingly, BMT is seen as the treatment of choice for first-remission adult patients with acute leukemia. BMT involves a decision to accept a potentially fatal treatment during a period of adjustment to the initial illness diagnosis. BMT involves potentially lethal doses of chemotherapy and frequently total body irradiation (TBI), followed by a prolonged period of isolation while the transplanted marrow engrafts. This isolation period is often accompanied by intercurrent infection. Following discharge from the BMT unit, there is a further period of susceptibility to infection and complications, such as graft-vs.-host disease (GVHD), recurrence of leukemia, and psychosocial occurrence of adVOLUME 35 • NUMBER 4 • JULY - AUGUST 1994

justment difficulties. With the associated high mortality and high morbidity, BMT is clearly a stressful treatment. In psychological studies of BMT, the main finding has been a remarkably low prevalence of psychiatric illness and psychological morbidity. In an earlier study, we found that prevalence of depressive illness was no higher than in other medically ill patient groups, that as a group there was no higher level of psychosocial morbidity than in mixed cancer patients, and that the group was characterized by psychological attitudes that have previously been shown to be associated with good prognosis in other cancer patient groupS.2..1 This finding raised the

Received April 10. 1992: revised June 3. 1992: accepted December 7. 1992. From the Department of Psychological Medicine. SI. Cadoc's Hospital. Caerleon. University of Wales College of Medicine. Heath Park. Cardiff. United Kingdom. Address reprint requests to Dr. Jenkins MRCPsych.. Consultant-Liaison Psychiatrist. SI. Cadoc's Hospital. Caerleon. Newport, Gwen! NP6 IXQ. UK. Copyright © 1994 The Academy of Psychosomatic Medicine.

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Psychosocial Morbidity in Adult BMT Recipients

possibility that persons with poorer scores on some standard psychiatric screening tests, which were associated with depressive illness, were dying during the BMT procedure, or alternatively that their scores on the Mental Attitude to Cancer Scale (MACS) were unstable over the BMT procedure and improved post-BMT. In common with most other studies,4-7 this study was retrospective, and these surprising findings raised the possibility that persons with poor psychosocial health were not surviving the BMT procedure. A recent American study lends support to this hypothesis, which found that patients with depressed mood and low social support had poorer prognosis. K To investigate this possibility further, we conducted this prospective study. METHODS Forty adult patients undergoing BMT at the University of Wales College of Medicine were prospectively recruited between September 1989 and September 1990. Our sample represented all patients considered for BMT during the study period. All patients were asked to complete the Hospital Anxiety and Depression Scale (HADS),'J the MACS. 1O and the Psychosocial Adjustment to Illness Scale (PAIS)1 on or before admission to the BMT unit. The HADS and PAIS are well-known instruments. The MACS was devised to measure predominant psychological coping style, and scores are derived in five domains: fighting spirit (FS), helplessness (H), anxious preoccupation (AP), fatalism (F), and avoidance (A V). Transformation to normal scores enables the determination of the predominant coping style, and this style has been found to be of prognostic significance in some studies. III The patients were then interviewed by using the Composite International Diagnostic Interview (CIDI).II a highly structured interview for diagnosis. by one of the investigators (HL). The patients were interviewed and completed the psychometric assessments prior to conditioning chemotherapy and TBI. but immediately before transplantation. 362

During the study period, all patients received a similar conditioning and TBI regimen. As in our previous study, the majority received a standard chemotherapeutic induction and TBI. Although a small minority received differing regimens, no differences were noted on the psychometric instruments between physical treatment groups. At I-month postdischarge from the unit. the surviving patients were asked to complete the same battery of psychometric instruments. All patients were reinterviewed using the CIDI. At 6-month postdischarge, the surviving patients were again asked to complete the psychometric tests. Those scoring > 13 on the HADS were reinterviewed using the CIDI. The data was analyzed by using the MINITAB computer program, primarily by descriptive statistical presentation and, where appropriate, by paired I-testing, chi-square, or Fisher exact test. During the study period, from initial inclusion in the study to its completion 6 months postdischarge. no study participant received psychiatric treatment in order to establish the effects, if any. of any psychological or psychiatric distress in this patient group. Ethical approval for this study was gi ven by the Joint Ethics Committee of the South Glamorgan Health Authority. RESULTS Patient Demographics and Disease State A total of 40 patients between the ages of 15 and 56 (mean = 34.7 years) were included in the study. There were 17 women and 23 men. Twelve persons had acute myeloid leukemia, 8 acute lymphoblastic leukemia, 6 nonHodgkin's lymphoma, 4 Hodgkin's lymphoma, 3 aplastic anemia, 3 chronic myeloid leukemia, and 4 other conditions (blastocytic leukemia, multiple immune deficiency, chronic granulocytic leukemia, and an unknown type of leukemia). Analysis of length of stay, total HADS, and age by disease type showed no statistically sigPSYCHOSOMATICS

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nificant differences. The presence of depression or anxiety as diagnosed by the CIDI were similar, and death at I and 6 months appeared to be evenly distributed across the differing disease groupings. The average length of stay on the BMT unit was 38.6 days (standard deviation = 18.8, 1st quartile = 28 days, 3rd quartile = 47 days). Age and sex did not have a significant influence on length of stay or survival at the follow-up points. Patients Recruited Of the 40 patients recruited, 4 did not undergo BMT, 2 died awaiting treatment. and 2 had not been treated by the time study recruitment was terminated. Thirty-six individuals underwent BMT, 28 of whom completed psychometric testing. Four declined to complete the questionnaires, 3 were too ill to complete questionnaires, and I could not read English. Thirty-one patients were interviewed pre-BMT using the CIDI. Two persons refused to be interviewed, 2 were too ill to complete the interview, and I individual died suddenly before the interview.

One-month Postdischarge. Of the 36 individuals undergoing BMT, 4 died during treatment, and the surviving 32 individuals were all reinterviewed using eIDI I-month postdischarge. Fifteen of these individuals did not complete the psychometric testing, 8 declined, 5 were or became too ill to complete the full questionnaires, and I could not read English. No difference in length of stay, pretransplant total HADS, sex, age, or percentage diagnosed by eIDI was demonstrated between those declining to complete the tests and those who did. Those who declined did not differ on their scores for FS or AP, but they had higher scores for H and significantly higher scores on F. This suggested that they may have been a more negative-oriented group pretransplant. No specific reasons for declining assessment were given. VOLUME 35 • NUMBER 4 • JULY - AUGUST 1994

Six-month Postdischarge. Of the 32 BMT recipients surviving at I-month postdischarge, II died before the 6-month follow-up. The 21 surviving individuals were asked to complete the psychometric tests, of whom 12 did so; 7 refused, I was too ill, and I could not read English. Those who refused had also declined at the I-month assessment, but they cited no specific reasons. One person who scored above 13 on the HADS, which suggested the presence of probable psychiatric ill health, was reinterviewed. This had been shown to be a suitable cutoff in our previous study.~ PAIS Results Of the 36 patients who underwent transplantation, 30 had completed the PAIS beforehand. Seventeen of the 29 patients who were surviving at I month completed the PAIS, and 12 of the 23 patients alive at the 6-month stage completed the PAIS (Table I). The woman patients had significantly higher scores for health care orientation (HCO) and sexual impairment pretransplant, but no effect of sex on any other domain was noted. Posttransplant scores did not differ by sex. Age and length of stay were not correlated with scores on any domain either pre- or posttransplant. TABLE I. Psychosocial Adjustment to Illness Scale raw scores Means+ SD Postdischarge: Postdischarge: Pretransplant I month 6 months (n =30/36) (n =17129) (n =12123) HCO VOC OOM SEX FAM SOC PSY

4.97 ± 3.08 8.41 ± 3.67 3.53 ± 2.46 5.11 ± 3.91 1.73 ± 2.13 6.03 ±4.21 5.83 ± 3.62

4.82 ± 3.36 9.06 ±4.11 5.00 ±2.94 3.33 ± 3.31 1.94± 1.48 6.65 ±4.58 5.12 ± 5.63

4.67 ± 1.87 7.25 ±6.03 3.58 ± 2.64 3.82 ± 3.97 0.75 ± 1.48 3.92 ± 3.42 4.92±5.11

Note: HCO =Heahh care orientation: VOC = vocation: OOM =domestic: SEX =sexual adjustment: FAM =family: SOC = social adjustment: PSY = psychological adjustment. Higher scores indicate greater impairment.

36.~

Psychosocial Morbidity in Adult BMT Recipients

Total HADS correlated with worse scores vocationally and psychologically (PSY) at all stages. At 6 months, total HADS also correlated with worse domestic (DOM) and sexual scores. Associations with other variables were assessed by using paired I-tests, with a signficance level of P < 0.05. A CIDI diagnosis of anxiety was significantly associated with higher HCO and PSY scores pretransplant. Anxiety was associated with worse DOM scores only at I-month follow-up. Anxiety was associated with markedly higher scores in all domains at 6 months but only achieved significance on DOM scores. A CIDI diagnosis of depression was associated with higher PSY scores pretransplant but apparently had no significant effect on posttransplant scores. Death at the I-month marker was not associated with differing scores on any domain pretransplant. Death at the 6-month marker was significantly associated with higher HCO scores and lower sexual impairment scores pretransplant.

Hospital Anxiety and Depression Scale Results At pretransplant, 9 out of 30 patients' total HADS were> 13 (30%), which we have previously been shown to be a good cutoff for detecting psychiatric illness in this group.2 At I month, 2 of the 13 (\4.5%) respondents scored above 13; at 6 months, 2 of II (18%) respondents scored above 13. Pretransplant total HAD score did not correlate with length of stay in the unit. Pretransplant scores correlated poorly (r =0.52) with I-month posttransplant scores, but the scores correlated well with 6-month scores (r = 0.77). High pretransplant scores were not associated with death at 1- or 6-month follow-up (X 2 = 0.20, NS). At all stages, high correlations were observed between subscale scores (pretransplant: r =0.65; I month postdischarge: r = 0.62; 6month postdischarge: r =0.90), as in our previous study,2 so the results were not analyzed using the two described subscales for anxiety and depression. Mental Attitude to Cancer Scale Results

Composite International Diagnostic Interview Results Of the 31 individuals who were interviewed pretransplant using CIDI, 10 met criteria for generalized anxiety disorder and 5 for major depressive disorder.

Correlations between the pre-BMT and post-BMT scores for those who completed assessment at both pretransplant and each followup stage varied, but none achieved significance at the P < 0.05 level (Table 2). Scores in the MAC domains did not correlate with length of stay or age. The woman

TABLE 2. Mental Attitude to Cancer Scale scores and correlation Pre·BMT Domains Fighting spirit Helplessness Anxious preoc<:upalion Fatalism Avoidan<:e

(n =29)

53.1 ± 5.72 9.14± 2.95 20.9 ± 4.22 16.6± 5.27 1.52 ±0.80

Means±SD I month post-BMT (n

=16)

52.4 ± 5.48 (0.65) 8.81 ± 2.76 (0.86) 22.0 ± 3.63 (0.47) 14.9 ± 3.78 (0.80) 1.86 ± 0.66 (0.09)

6 months post-BMT (n = II) 52.4 ± 6.0 (0.26) 9.18 ± 2.56 (0.10) 22.0 ± 3.82 (0.20) 16.4 ± 3.78 (0.67) 2.09 ± 0.54 (0.66)

BMT = bone marrow transplant. • Numbers in parens are P-values. P> 0.05 in all cases.

Nolt,:

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patients were likely to have higher F scores (t-test P< 0.0 I) pretransplant. There was no significant difference between patients who were deceased at follow-up and those alive in terms of the scores from any domain. The patients diagnosed with anxiety disorders using the CIO. criteria had slightly higher scores on AP (t-test P =0.20), but not in other domains. Depressive disorders as diagnosed by CIDI were associated with poorer prognostic attitudes; lowered FS (t-test P< 0.0 I); and raised H, AP, and F (all (-tests P < 0.0 I). The importance of these associations is uncertain in depressive disorder and for both anxiety and depression. Thf' !Jrl>c-:~e of diagnosable anxiety and/or der .essic I t ad no significant effect on length of stay a, d was not affected significantly by age or sex. The patients diagnosed with anxiety or depression were not significantly less likely to survive at 1- or 6-month follow-up than those without psychiatric morbidity. Psychiatric diagnoses assigned by the CIDI at the pretransplant stage and at the second interview I-month postdischarge remained stable in the absence of specific psychiatric treatments, suggesting that CIOI identifies true morbidity. Patient demographic data at each stage of evaluation as well as length of stay is presented in Table 3. TABLE 3, Patient demographics. psychometric data. and length of stay at each stage of evaluation (N = 40' Gender Psychometric data None completed Pretransplant data only One-month postdischarge + pretransplanl data Six-month postdischarge + I-month + pretransplanl data

Length of stay (days'

F

M

Age

7

3 7

27

5

36.4

49.6 36.1

6

0

31.3

36.7

7

5

38.2

35.0

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DISCUSSION The present study examined the effect of a number of psychological factors on BMT patients who were recruited prospectively and studied over the transplant period and for 6 months postdischarge. Although previous studies 2 have shown that patients posttransplant are no different from other medical cancer populations, raising the possibility that psychologically unhealthy individuals have poorer outcomes than psychologically healthy patients, our study did not confirm this hypothesis. The present study also failed to show that psychiatric illness in the form of depression was associated with poorer outcome, as had been found in a recent American study. x This could be due to the limited length of follow-up in the current study compared with that of the U.S. study, which typically followed patients for as long as 2 years. The present study failed to demonstrate any effect of pretransplant psychiatric illness on length of stay. The interpretation of the PAIS scores is complicated by the high numbers of patients who failed to complete the test posttransplant. The study also failed to demonstrate a clear association between adjustment and mortality. Particular interest in the study was paid to the question of whether patient attitudes toward the cancer or other illness affect survival because such mental attitudes have been shown to be associated with prognosis in other cancer groups. Disappointingly, no correlation with length of stay or mortality was demonstrated over the study period for these attitudinal variables. Another problem was that scale scores for the MACS questionnaire were unstable over the study period, raising the possibility that they may not be independent of physical condition and other illness related variables. This suggests that at this time of extreme stress and readaptation, patients' attitudes toward their underlying malignancy vary. This in tum argues against the concept that the MACS scores measure stable attitudinal factors associated with prognosis in this patient population. 3M

Psychosocial Morbidity in Adult BMT Recipients

In common with our previous study.2 depressive illness was shown to be significantly associated with negative cognitive attitudes. as evidenced by reduced fighting spirit and raised anxious preoccupation. fatalism. and helplessness. It is possible that the scale is merely measuring cognitive changes due to depression rather than attitudinal variables. reflecting cognitive style in an individual. If this is the case. then normalization could be expected through standard psychopharmacological treatmentsl~ rather than complex cognitive psychotherapy. U The study showed that psychosocial adjustment to illness was good in the patients studied and that psychosocial function remained relatively stable over the study period. In keeping with our retrospective results. depression was associated with greater degrees of impairment. which would suggest that treatment could improve quality of life posttransplant. The results of this study indicate that properly conducted. random studies of the various psychological treatment alternatives should be conducted prior to their advocacy. These may include various interventions such as psychopharmacologic intervention, cognitive or other psychotherapies. and social interventions such as support groups or family intervention. A major limitation of such studies is the relatively small numbers of BMT patients at individual sites. together with their heterogeneity by physical disease, which could be

overcome by multicenter studies. One important reason for the negative results reported here is the limited length of time of follow-up of our patients to date. As survival extends. late complications. such as GVHD. leukemia recurrence. complications of immunosuppressive therapy, and cataracts due to TBI. may become more prevalent. leading to new psychological morbidity. Such complications will complicate the analysis of the effects of psychological factors such as the MACS scores in this patient group. Relatively well-established and valid concepts such as major depressive disorder may be of greater utility in prediction in the longer term. Although the analysis of this study has shown little predictive power for psychological variables, it is quite clear that depressive illnesses are prevalent in this patient population, as in other medical groups. The association of such treatable disorders with psychosocial impairment and reduced quality of life is a strong indication for evaluation and treatment of the depression. Also. the study supports the use of a simple self-rating scale such as the HADS to screen BMT candidates. The fact that depression is also associated with negative cognitive set, which has been shown in other groups to be important prognostically, strengthens the case for such treatment. even if the attitudes are not shown to be as important in this patient population.

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6. Alby N. Devergie A. Vii mer E. et al: Psychosocial adjustment in 120 patients treated with bone marrow transplantation for leukaemia or aplastic anaemia. Paper presented at poster session of the 4th International Symposium on Therapy for Acute Lymphoblastic Leukemia. Rome. Italy. 1987 7. Andrykowski MA. Henslee PJ. Barnett RL: Longitudinal assessment of psychosocial functioning of adult survivors of allogeneic bone marrow transplantation. Bone Marrow Transplant 1989: 4:505-509 8. Colon EA. Callies AL. Pokin MK.et al: Depressed mood and other variables related to bone marrow transplantation survival in acute leukemia. Psychosomatics 1991: 32:420-425 9. Zigmond AS. Snaith RP: Hospital anxiety and depres-

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sion scale. Acta Psychiatr Scand 1983; 67:361-370 10. Greer S. Watson M: Mental attitude to cancer: its measurement and prognostic importance. Cancer Surv 1987; 6:439-453 II. Wittchen H-U. Robins LN. Cottier LB. et al: Crosscultural feasibility and sources of variance of the Composite International diagnostic interview (CIO!).

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Br J Psychiatry 1991; 159:645-652 12. Stoudemire A. Moran MG. Fogel BS: Psychotropic drug use in the medically ill. part I. Psychosomatics 1990; 31 :377-391 13. Moorey S. Greer S: Psychological Therapy for Patients With Cancer. Oxford. England. Heinneman Medical Books. 1989

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