A Retrospective Study of Psychosocial Morbidity in Bone Marrow Transplant Recipients PETER L. JENKINS, M.R.C.PSYCH. A. LININGTON, M.R.C.P. J.A. WHITTAKER, F.R.C.P., ER.C.PATH.
Of the 44 hone marrow transplant recipients asked to participate in this study. JJ completed psychometric instruments. Twenty-fil'e patients had hoth unstructured clinical interl'iews and interl'iews using a structured diagnostic instrument (the Composite Jflfernational Diagnostic Jflfen·iew). There were no differences hetween allogeneic and autogenic transplant recipients. Ol'erall. patieflfs demonstrated adjustmeflf comparahle with other medical patients. A high premlence ofdepression (40%) was shown to he associated with impaired fill/ction. The implications ofthese findings are discussed.
A 1I0geneic bone marrow transplantation is an .L"\.increasingly common treatment for patients with leukemia and associated bone marrow disorders. The great majority of adult transplants are done in first remission at a time when good results are expected. The procedure is traumatic and is associated with high morbidity and mortality. Long-term survival figures vary according to the disease and stage at which transplantation is performed. with most major centers reporting projected 5-year survival rates of 50%-60%.1-.1 Autotransplantation. which utilizes the patient's own remission bone marrow. has become the treatment of choice for patients under 60 years of age who do not have a matched sibling donor. This relatively recent change in practice has reduced severe illness and deaths previously associated with graft vs. host disease (GVHD). but relapse of leukemia is seen much more often. with overall survival rates not significantly different from those in allogenic transplantation.~ Considerable physical and psychological morbidity related to the stages of induction chemotherapy and to the conditioning preparation may result prior to transplantation. Induction chemotherapy. required to obtain remission. uses VOLUME 32· NUMBER 1 • WINTER 1991
high doses of cytotoxic drugs and is often associated with life-threatening septicemia during periods of neutropenia. Conditioning chemotherapy almost always includes lethal doses of cytotoxic drugs used to totally ablate residual disease and to suppress the immune system. Many patients also receive total body irradiation (TBI). which often causes severe vomiting and is sometimes associated with an acute confusional state; in children it has been reported to lead to long-term cognitive deficits. ~ Following this period of induction. the transplant itself can seem almost an anticlimax. h but there follows a period of isolation in a germ-free environment. Environmental deprivation has been shown to have a range of psychological consequences. such as disorientation. 7 The time Received August 30. 19!19; revised November 27. 19!19; accepled December 29. 1989. From the Depanmenls of Psychological Medicine and Haematology. University of Wales College of Medicine. Heath Park. Cardiff. South Wales. Address reprint requesls 10 Dr. Jenkins. Depanment of Psychological Medicine. University of Wales College of Medicine. Heath Park. Cardiff. South Wales CF4 4XN. Copyright © 1991 The Academy of Psychosomatic Medicine.
Psychosocial Morbidity
spent in isolation is variable, depending on how successfully the donor tissue engrafts and on whether serious complications from GVHD supervene. Most patients stay between 4 and 6 weeks. This is, therefore, a period of prolonged uncertainty in which many psychological issues (e.g., an ambivalent relationship between patient and donor, social problems such as interpersonal difficulties within the family, and physical morbidity such as delirium and infections) may emerge as additional stressors. The treatment phase from diagnosis of malignancy to successful transplantation usually lasts about 2 years, which involves considerable adjustments in the organization of patients' lives-not only psychologically, but also practically-often involving the loss of a job, income, and role within the family. It is well established that patients with cancer have an increased psychiatric morbidity.K Retrospective studies have shown persistent emotional distress and lowered self-esteem, as well as a decrease in life satisfaction (despite youth), a decrease in vocational activity, and a decrease in the presence of intimate relationships in 15%25% of bone marrow transplant recipients. 9 Other studies have also shown severe emotional strain and persisting post-discharge emotional and sexual difficulties. 10 We postulated that psychiatric morbidity in those patients with cancer who also undergo bone marrow transplantation would be increased, due to the additional stressors peculiar to the transplant procedure. Previous studies have already suggested that the psychosocial adjustment of patients undergoing allogeneic, rather than autologous, transplant is impaired due to the increased incidence ofGVHD. " We attempted to relate the onset of psychological problems to the stages in the transplant procedure outlined by Brown and Kelly. 6 It was felt that this could guide the timing of any future intervention that was considered necessary. Most previous studies have involved small numbers of patients, leading to possible selection bias due to referral factors. In addition, they have focused on poorly defined psychodynamic concepts and have failed to utilize valid and reliable psychometric instruments or structural interviews based upon operational diagnostic criteria. 66
These shortcomings limit the comparability of studies between different centers. To address these important methodological issues, we undertook a retrospective study of all surviving bone marrow transplant recipients who received grafts between July 1982 and July 1988 at University Hospital of Wales. We used standardized psychometric rating scales of proven reliability and validity and a structured diagnostic interview, the Composite International Diagnostic Interview (CIDI), together with an unstructured clinical interview. METHODS Transplant recipients were asked to participate in the study after they had been discharged from the transplant unit and were living at home. Purpose of the study was explained, and each individual gave informed consent. Participants completed the Psychosocial Adjustment to Illness Scale (PAIS),'~ the Hospital Anxiety and Depression Scale (HAD), I.l and Eysenck Personality Questionnaire (EPQ).'4 Interviews were conducted (by Pol. or A.L.) in a private office or the individual's home. Initial interviews were conducted jointly. The first part of the interview focused on the patient's illness, with exploration of the feelings of each of the eight stages postulated by Brown and Kelly.1> A standard psychiatric history was elicited, and a clinical mental status examination. including the Mini-Mental State examination. " was performed. Clinical diagnoses were assigned according to DSM-III criteria by the interviewer. Each individual was then interviewed using the somatization and anxiety and depression modules of the CIDI. 16 Interview time averaged 6090 minutes. Psychometric data were analyzed by utilizing paired t tests of significance, and data derived from this study were compared with the published data regarding these tests.I~-14 Analysis of PAIS scores was conducted using raw scores. CIDI was analyzed using a computer program that replicated the handscoring method used in its predecessor instrument, the Diagnostic Interview Schedule. 16 PSYCHOSOMATICS
Jenkins et al.
Ethical approval was obtained from the Joint Ethics Committee of the University of Wales College of Medicine and the South Glamorgan Health Authority. RESULTS All 44 surviving transplant recipients older than 15 were asked to participate in the study by letter or personal approach; II declined to participate. No differences were detected between those who chose to participate in terms of age. sex. and duration since transplant or physical illness. Thirty-three individuals completed the questionnaires. and 25 of these were interviewed. Eight did not request an appointment for interview. There were 17 men and 16 women who completed questionnaires and I I men and 14 women who were interviewed. Analysis of the responses for those interviewed or not interviewed showed no significant differences between the groups. The mean age was 36 (range 22-62). Analysis of age by sex. and age by auto- or allogeneic transplant type. showed no differences. In the whole group of 44 patients. there were 22 autologous and 22 allogeneic transplant recipients. There were 17 autologous transplant recipients and 16 allogeneic transplant recipients who completed the questionnaires: 13 autologous and 12 allogeneic recipients were interviewed. We predicted that allogeneic patients who might have GYHD would be more ill and thus more likely to have psychiatric symptomatology. Only two patients in the allogeneic group had severe GYHD at time of interview. but severity was assessed only subjectively. Comparison of the scores of anxiety. depression. and each subscale of the PAIS showed no significant differences between the groups. Of the 25 patients interviewed. 2 had had 2 autologous transplants for acute myeloid leukemia: 13 patients had acute myeloid leukemia: 4 chronic myeloid leukemia: 3 lymphomas; 2 acute lymphocytic leukemia: 2 aplastic anemia; and I myeloma. Patients were interviewed a mean 25.6 months after receiving their transplant (range 3-67). The average length of stay in the unit was 8 weeks. VOLUME .12· NUMBER I • WINTER 1991
CIDI assigned psychiatric diagnoses to the allogeneic and autogenic patients. respectively. as follows: generalized anxiety disorder: 7.9 = 16; major depressive episode: 2.5 =7: previous major depression: 3.5 =8: clinical anxiety: 2.1 = 3: and current major depression: 1.4 =5. The frequency of diagnosis between the two groups was assessed using Fisher's Exact test. and no significant difference was found. The higher rate of anxiety detected by CIDI may reflect either a problem with the early version of the instrument used or a tendency by the clinicians to minimize anxiety. As no statistically significant differences between the autologous and allogeneic transplant groups were demonstrated. we then pooled the results of the two groups for further analysis. Eysenck Personality Questionnaire The Eysenck Personality Questionnaire provides two dimensions of personality. extroversion (E) and neuroticism (N). which are felt to be trait variables associated with predisposition to certain psychological responses. For example. high N scores have been shown to predispose to depression. A lie (L) scale is also included which reflects "faking good," No correlation between E. N. or Lscores was observed with either HAD subscores or any of the PAIS domain scores. No difference in E. N. or L scores between those diagnosed as depressed and those not diagnosed was shown. The groups' mean Nand E scores did not differ significantly from published values for a normal population group.14 Hospital Anxiety and Depression Scale (HAD) The HAD scale was designed to measure anxiety and depression in medical patients and is a 14-item self-report scale. L1 It can also be used to screen for anxiety and depression. The average scores in this population were-depression 4.39±4.79 (mean±SD) and anxiety 6.51±4.30. We noted a strong correlation between the scores on each scale (Pearson 0.757.
p=O.OOO). 67
Psychosocial Morbidity
Psychosocial Adjustment to IIIness Scale (PAIS) Data
EVALUATION OF STAGES OF TREATMENT
The PAIS is a 46-item self-report scale that evaluates psychological and social function in 7 domains: Health Care Orientation, Vocational Environment, Domestic Environment, Sexual Relationship, Family Relationships, Social Environment, and Psychological Distress. The instrument has been well validated and has good reliability and also appropriate control groups; 12 higher scores reflect increasing degrees of impairment. Pooled data for each domain of the PAIS were examined. It was found that the group overall did not differ from the published norms of a mixed cancer group. 12 Elevated scores on subscales relating to family relationships, social relationships, and psychological morbidity were correlated with elevated scores on the depression scale of the HAD scale (Pearson 0.76, p
Of the 44 hone marrow transplant recipients asked to participate in this study. JJ completed psychometric instruments. Twenty-fil'e patients had hoth unstructured clinical interl'iews and interl'iews using a structured diagnostic instrument (the Composite Jflfernational Diagnostic Jflfen·iew). There were no differences hetween allogeneic and autogenic transplant recipients. Ol'erall. patieflfs demonstrated adjustmeflf comparahle with other medical patients. A high premlence ofdepression (40%) was shown to he associated with impaired fill/ction. The implications ofthese findings are discussed.
A 1I0geneic bone marrow transplantation is an .L"\.increasingly common treatment for patients with leukemia and associated bone marrow disorders. The great majority of adult transplants are done in first remission at a time when good results are expected. The procedure is traumatic and is associated with high morbidity and mortality. Long-term survival figures vary according to the disease and stage at which transplantation is performed. with most major centers reporting projected 5-year survival rates of 50%-60%.1-.1 Autotransplantation. which utilizes the patient's own remission bone marrow. has become the treatment of choice for patients under 60 years of age who do not have a matched sibling donor. This relatively recent change in practice has reduced severe illness and deaths previously associated with graft vs. host disease (GVHD). but relapse of leukemia is seen much more often. with overall survival rates not significantly different from those in allogenic transplantation.~ Considerable physical and psychological morbidity related to the stages of induction chemotherapy and to the conditioning preparation may result prior to transplantation. Induction chemotherapy. required to obtain remission. uses VOLUME 32· NUMBER 1 • WINTER 1991
high doses of cytotoxic drugs and is often associated with life-threatening septicemia during periods of neutropenia. Conditioning chemotherapy almost always includes lethal doses of cytotoxic drugs used to totally ablate residual disease and to suppress the immune system. Many patients also receive total body irradiation (TBI). which often causes severe vomiting and is sometimes associated with an acute confusional state; in children it has been reported to lead to long-term cognitive deficits. ~ Following this period of induction. the transplant itself can seem almost an anticlimax. h but there follows a period of isolation in a germ-free environment. Environmental deprivation has been shown to have a range of psychological consequences. such as disorientation. 7 The time Received August 30. 19!19; revised November 27. 19!19; accepled December 29. 1989. From the Depanmenls of Psychological Medicine and Haematology. University of Wales College of Medicine. Heath Park. Cardiff. South Wales. Address reprint requesls 10 Dr. Jenkins. Depanment of Psychological Medicine. University of Wales College of Medicine. Heath Park. Cardiff. South Wales CF4 4XN. Copyright © 1991 The Academy of Psychosomatic Medicine.
Psychosocial Morbidity
spent in isolation is variable, depending on how successfully the donor tissue engrafts and on whether serious complications from GVHD supervene. Most patients stay between 4 and 6 weeks. This is, therefore, a period of prolonged uncertainty in which many psychological issues (e.g., an ambivalent relationship between patient and donor, social problems such as interpersonal difficulties within the family, and physical morbidity such as delirium and infections) may emerge as additional stressors. The treatment phase from diagnosis of malignancy to successful transplantation usually lasts about 2 years, which involves considerable adjustments in the organization of patients' lives-not only psychologically, but also practically-often involving the loss of a job, income, and role within the family. It is well established that patients with cancer have an increased psychiatric morbidity.K Retrospective studies have shown persistent emotional distress and lowered self-esteem, as well as a decrease in life satisfaction (despite youth), a decrease in vocational activity, and a decrease in the presence of intimate relationships in 15%25% of bone marrow transplant recipients. 9 Other studies have also shown severe emotional strain and persisting post-discharge emotional and sexual difficulties. 10 We postulated that psychiatric morbidity in those patients with cancer who also undergo bone marrow transplantation would be increased, due to the additional stressors peculiar to the transplant procedure. Previous studies have already suggested that the psychosocial adjustment of patients undergoing allogeneic, rather than autologous, transplant is impaired due to the increased incidence ofGVHD. " We attempted to relate the onset of psychological problems to the stages in the transplant procedure outlined by Brown and Kelly. 6 It was felt that this could guide the timing of any future intervention that was considered necessary. Most previous studies have involved small numbers of patients, leading to possible selection bias due to referral factors. In addition, they have focused on poorly defined psychodynamic concepts and have failed to utilize valid and reliable psychometric instruments or structural interviews based upon operational diagnostic criteria. 66
These shortcomings limit the comparability of studies between different centers. To address these important methodological issues, we undertook a retrospective study of all surviving bone marrow transplant recipients who received grafts between July 1982 and July 1988 at University Hospital of Wales. We used standardized psychometric rating scales of proven reliability and validity and a structured diagnostic interview, the Composite International Diagnostic Interview (CIDI), together with an unstructured clinical interview. METHODS Transplant recipients were asked to participate in the study after they had been discharged from the transplant unit and were living at home. Purpose of the study was explained, and each individual gave informed consent. Participants completed the Psychosocial Adjustment to Illness Scale (PAIS),'~ the Hospital Anxiety and Depression Scale (HAD), I.l and Eysenck Personality Questionnaire (EPQ).'4 Interviews were conducted (by Pol. or A.L.) in a private office or the individual's home. Initial interviews were conducted jointly. The first part of the interview focused on the patient's illness, with exploration of the feelings of each of the eight stages postulated by Brown and Kelly.1> A standard psychiatric history was elicited, and a clinical mental status examination. including the Mini-Mental State examination. " was performed. Clinical diagnoses were assigned according to DSM-III criteria by the interviewer. Each individual was then interviewed using the somatization and anxiety and depression modules of the CIDI. 16 Interview time averaged 6090 minutes. Psychometric data were analyzed by utilizing paired t tests of significance, and data derived from this study were compared with the published data regarding these tests.I~-14 Analysis of PAIS scores was conducted using raw scores. CIDI was analyzed using a computer program that replicated the handscoring method used in its predecessor instrument, the Diagnostic Interview Schedule. 16 PSYCHOSOMATICS
Jenkins et al.
Ethical approval was obtained from the Joint Ethics Committee of the University of Wales College of Medicine and the South Glamorgan Health Authority. RESULTS All 44 surviving transplant recipients older than 15 were asked to participate in the study by letter or personal approach; II declined to participate. No differences were detected between those who chose to participate in terms of age. sex. and duration since transplant or physical illness. Thirty-three individuals completed the questionnaires. and 25 of these were interviewed. Eight did not request an appointment for interview. There were 17 men and 16 women who completed questionnaires and I I men and 14 women who were interviewed. Analysis of the responses for those interviewed or not interviewed showed no significant differences between the groups. The mean age was 36 (range 22-62). Analysis of age by sex. and age by auto- or allogeneic transplant type. showed no differences. In the whole group of 44 patients. there were 22 autologous and 22 allogeneic transplant recipients. There were 17 autologous transplant recipients and 16 allogeneic transplant recipients who completed the questionnaires: 13 autologous and 12 allogeneic recipients were interviewed. We predicted that allogeneic patients who might have GYHD would be more ill and thus more likely to have psychiatric symptomatology. Only two patients in the allogeneic group had severe GYHD at time of interview. but severity was assessed only subjectively. Comparison of the scores of anxiety. depression. and each subscale of the PAIS showed no significant differences between the groups. Of the 25 patients interviewed. 2 had had 2 autologous transplants for acute myeloid leukemia: 13 patients had acute myeloid leukemia: 4 chronic myeloid leukemia: 3 lymphomas; 2 acute lymphocytic leukemia: 2 aplastic anemia; and I myeloma. Patients were interviewed a mean 25.6 months after receiving their transplant (range 3-67). The average length of stay in the unit was 8 weeks. VOLUME .12· NUMBER I • WINTER 1991
CIDI assigned psychiatric diagnoses to the allogeneic and autogenic patients. respectively. as follows: generalized anxiety disorder: 7.9 = 16; major depressive episode: 2.5 =7: previous major depression: 3.5 =8: clinical anxiety: 2.1 = 3: and current major depression: 1.4 =5. The frequency of diagnosis between the two groups was assessed using Fisher's Exact test. and no significant difference was found. The higher rate of anxiety detected by CIDI may reflect either a problem with the early version of the instrument used or a tendency by the clinicians to minimize anxiety. As no statistically significant differences between the autologous and allogeneic transplant groups were demonstrated. we then pooled the results of the two groups for further analysis. Eysenck Personality Questionnaire The Eysenck Personality Questionnaire provides two dimensions of personality. extroversion (E) and neuroticism (N). which are felt to be trait variables associated with predisposition to certain psychological responses. For example. high N scores have been shown to predispose to depression. A lie (L) scale is also included which reflects "faking good," No correlation between E. N. or Lscores was observed with either HAD subscores or any of the PAIS domain scores. No difference in E. N. or L scores between those diagnosed as depressed and those not diagnosed was shown. The groups' mean Nand E scores did not differ significantly from published values for a normal population group.14 Hospital Anxiety and Depression Scale (HAD) The HAD scale was designed to measure anxiety and depression in medical patients and is a 14-item self-report scale. L1 It can also be used to screen for anxiety and depression. The average scores in this population were-depression 4.39±4.79 (mean±SD) and anxiety 6.51±4.30. We noted a strong correlation between the scores on each scale (Pearson 0.757.
p=O.OOO). 67
Psychosocial Morbidity
Psychosocial Adjustment to IIIness Scale (PAIS) Data
EVALUATION OF STAGES OF TREATMENT
The PAIS is a 46-item self-report scale that evaluates psychological and social function in 7 domains: Health Care Orientation, Vocational Environment, Domestic Environment, Sexual Relationship, Family Relationships, Social Environment, and Psychological Distress. The instrument has been well validated and has good reliability and also appropriate control groups; 12 higher scores reflect increasing degrees of impairment. Pooled data for each domain of the PAIS were examined. It was found that the group overall did not differ from the published norms of a mixed cancer group. 12 Elevated scores on subscales relating to family relationships, social relationships, and psychological morbidity were correlated with elevated scores on the depression scale of the HAD scale (Pearson 0.76, p
