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1936
Quality of Life for Adult Leukemia Survivors Treated
on Clinical Trials of Cancer and Leukemia Group B
during the Period 1971–1988
Predictors for Later Psychologic Distress
Donna B. Greenberg, M.D.1
Alice B. Kornblith, Ph.D.2
James E. Herndon, Ph.D.3
Enid Zuckerman, M.A.2
Charles A. Schiffer, M.D.4
Raymond B. Weiss, M.D.5
Robert J. Mayer, M.D.6
Silkaly M. Wolchok, Ph.D.2
Jimmie C. Holland, M.D.2
BACKGROUND. To identify predictors of psychosocial adjustment for survivors of
1
Department of Psychiatry, Massachusetts
General Hospital, Boston, Massachusetts.
2
Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center,
New York, New York.
3
Cancer and Leukemia Group B Statistical Office, Durham, North Carolina.
4
Department of Medicine, University of Maryland Cancer Center, Baltimore, Maryland.
5
Department of Medicine, Walter Reed Army
Medical Center, Washington, DC.
6
Department of Adult Oncology, Dana-Farber
Cancer Institute, Boston, Massachusetts.
Presented in abstract form in Greenberg DB, Kornblith AB, Herndon JE, Zuckerman E, Schiffer CA,
Weiss RB, et al. Quality of life of adult leukemia
survivors treated on clinical trials of the Cancer and
Leukemia Group B from 1971–1988: predictors
for later psychological distress [abstract 1668].
Proc Am Soc Clin Oncol 1995;14:508.
Research for CALGB 8963 was supported in
part by grants from the National Cancer Institute
(Research Grant CA31946) to the Cancer and
Leukemia Group B (Richard L. Schilsky, Chairman). Dr. Greenberg was supported by supported by Grant CA12449, Dr. Herndon was
supported by Grant CA33601, Dr. Schiffer was
supported by Grant CA31983, Dr. Weiss was
supported by Grant CA26806, and Dr. Mayer
was supported by Grant CA32291.
adult acute leukemia, the adaptation of 206 survivors (77% with acute myelogenous
leukemia, and 23% with acute lymphocytic leukemia) treated on any of 13 Cancer
and Leukemia Group B trials during the period 1971–1988 was examined.
METHODS. Survivors (median age, 41 years) who were at least 1 year from completion of all treatment (median, 5 years) were interviewed by telephone about psychologic symptoms; social, sexual, and vocational function; and beliefs about control over health. Standardized psychologic instruments were used to evaluate survivors’ responses.
RESULTS. Most survivors adapted well; however, 14% were 1.5 standard deviations
above normal on the Global Severity Index of the Brief Symptom Inventory. Predictors of greater psychologic distress included less education, younger age, anticipatory distress during chemotherapy treatment, and the combination of more
The following institutions participated in this
study: Bowman-Gray School of Medicine, Winston-Salem, North Carolina (M. Robert Cooper,
M.D., supported by Grant CA03927); DanaFarber Cancer Institute, Boston, Massachusetts
(George P. Canellos, M.D., supported by Grant
CA32291); Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire (L. Herbert
Maurer, M.D., supported by Grant CA04326);
Duke University Medical Center, Durham, North
Carolina (Jeffrey Crawford, M.D., supported by
Grant CA33601); Eastern Maine Medical Center,
Portland, Maine (supported by Grant CA
32291); Long Island Jewish Medical Center,
New Hyde Park, New York (Marc Citron, M.D.,
supported by Grant CA11028); Massachusetts
General Hospital, Boston, Massachusetts (Michael Grossbard, M.D., supported by Grant
CA12449); McGill Department of Oncology,
Montreal, Quebec, Canada (Brian LeylandJones, M.D.); Medical Center of Delaware, Newark Delaware; (Irving Berkowitz, M.D., supported by Grant CA45418); Mount Sinai School
of Medicine, New York, New York (James Holland, M.D., supported by Grant CA04457); New
York Hospital-Cornell Medical Center, New
York, New York (Ted Szatrowski, M.D., supported by Grant CA07968); North Shore University Hospital, Manhasset, New York (Daniel R.
Budman, M.D., supported by Grant CA35279);
q 1997 American Cancer Society
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Rhode Island Hospital, Providence, Rhode
Island (Louis A. Leone, M.D., supported by
Grant CA 08025); Roswell Park Memorial Institute, Buffalo, New York (Ellis Levine, M.D.,
supported by Grant CA02599); University of
California-San Diego, San Diego, California
(Stephen Seagren, M.D., supported by Grant
CA11789); University of Iowa Hospitals,
Iowa City, Iowa- (Gerald Clamon, M.D., supported by Grant CA47642); University of
Maryland Cancer Center, Baltimore, Maryland (Ernest Borden, M.D., supported by
Grant CA31983); University of Minnesota,
Minneapolis, Minnesota (Bruce Peterson,
M.D., supported by Grant CA16450); University of Missouri/Ellis Fischel Cancer Center,
Columbia, Missouri (Michael C. Perry, M.D.,
supported by Grant CA12046); Upstate Medical Center at Syracuse, Syracuse, New York
(Stephen L. Graziano, M.D., supported by
Grant CA21060); and Walter Reed Army
Medical Center, Washington, DC (Nancy
Dawson, M.D., supported by Grant CA26806.
Address for reprints: Donna B. Greenberg, M.D.,
Massachusetts General Hospital, 100 Blossom
St., Cox Building, Boston, MA 02114.
Received March 13, 1997; revision received
May 30, 1997; accepted May 30, 1997.
Leukemia Survivors Predictors of Distress/Greenberg et al.
1937
medical problems after treatment with poorer family function. Anticipatory nausea
and distress during chemotherapy predicted persistent visceral distress later, which
occurred with reminders of treatment. Anticipatory vomiting predicted a greater
tendency toward cancer-related intrusive thoughts and avoidance of reminders.
CONCLUSIONS. Patients experiencing anticipatory distress during treatment who
are younger and less educated should be monitored for depressive syndromes
later. Cancer 1997;80:1936–44. q 1997 American Cancer Society.
KEYWORDS: acute leukemia, survivor, quality of life, depression, anticipatory nausea.
S
urvivors of adult acute leukemia must adapt to the
sudden onset of life-threatening illness, long and
intensive treatment, fear of recurrence, psychologic
response to this trauma, and physical and neuropsychologic consequences of treatment, followed by the
psychologic and logistic problems of reentry into the
world in which they had been living prior to their diagnosis of leukemia.
To examine the psychosocial adaptation of survivors, we identified 206 patients who had been diagnosed with leukemia and treated on 1 of 13 clinical
trials conducted by the Cancer and Leukemia Group
B (CALGB) between 1971 and 1988. These patients
were survivors of treatment that predated serotoninantagonist antiemetics such as ondansetron and the
introduction of the extensive use of bone marrow
transplantation (BMT). Our goals in interviewing and
studying these patients were to describe psychosocial
and sexual problems of these survivors, to identify factors that predicted better adaptation, and to evaluate
the mediating role of current family environment,
philosophic outlook, and perception of control over
health.
Previous studies of leukemia survivors have not
found differences in those patients who did or did not
undergo BMT. Lesko et al. studied 70 adult survivors
of acute leukemia who were treated with conventional
chemotherapy alone (n Å 49) or with BMT (n Å 21).1
Those patients 5 years from treatment and healthy,
irrespective of treatment type, demonstrated overall
good psychologic and social adjustment. As might be
expected, the survivors’ level of psychiatric symptoms
was greater than those in a general physically healthy
sample but not comparable to a group with psychiatric
illness. In another study of 30 acute myelogenous leukemia (AML) survivors 5 – 6.5 years after diagnosis in
which 11 underwent BMT and 19 were treated with
conventional chemotherapy, no differences were
found between the treatment groups.2 Measures of
psychiatric symptoms on the Brief Symptom Inventory
(BSI) fell within the normal range for nonpsychiatric
patients. On a self-report measure of psychiatric
symptomatology, the CES-D, 17% of the total respond-
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ers had scores above the ‘‘clinical cutting’’ score for
depression.
Other studies focused only on those individuals
with acute leukemia who underwent BMT. The study
by Curbow et al. of 135 patients at least 6 months after
allogeneic BMT including 41% with acute leukemia
found that subjects reported more positive changes in
relationships and in existential psychologic domains
but negative changes in physical health.3 Negative
mood correlated with more negative changes in relationships and single marital status. Loss of physical
strength occurred in 58% of responders. Wolcott et al.4
found persistent emotional distress in 15 – 25% of 26
survivors of BMT for acute leukemia.
METHODS
Patients
Patients were eligible if they had been treated between
1971 – 1988 on any 1 of 13 CALGB protocols for patients
with newly diagnosed acute leukemia (CALGB 7113,
7121, 7221, 7421, 7521, 7612, 7721, 7921, 8011, 8221,
8321, 8513, or 8525). They had to be at least age 20
years at the time of the interview, English-speaking,
and off treatment for at least 1 year. Patients were
selected from a list of survivors across medical centers
and protocols who met these criteria. The number of
interviewed survivors of CALGB 8525,5 which had been
completed most recently, was limited to approximately 30% of the total number of participants so that
the study’s findings would not be skewed by a more
recently treated cohort of survivors.
Two hundred and six (75%) of 275 acute leukemia
survivors eligible for the study were interviewed from
July 1990 to July 1993. Reasons for not being able to
successfully interview survivors were refusal to be interviewed (11%), unable to locate (e.g., wrong telephone number, unlisted number, or no telephone)
(11%), and miscellaneous other reasons (4%). Sample
bias was evaluated in terms of gender and race to
determine whether the sample interviewed was representative of the entire eligible sample; no evidence
of sample bias in relation to these two variables was
found.
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CANCER November 15, 1997 / Volume 80 / Number 10
Research Procedures
Patient participation required approval by the center
principal investigator, the treating physician, and obtainment of informed consent from the patient. The
research interviewer explained the study when the patient was notified. If the patient agreed to participate,
the consent form and questionnaires were mailed, and
the telephone interview was scheduled. The consent
form was returned in advance. The interview itself,
based on the questionnaires, took approximately 1
hour. The same technique had been used with Hodgkin’s disease survivors on CALGB protocols.6
Measures
Survivors’ psychosocial status was evaluated using the
following measures.
The Psychosocial Adjustment to Illness Scale (SelfReport) (PAIS-SR)7 is an inventory of adjustment to
illness with seven dimensions: health care orientation,
vocational environment, domestic environment, sexual relationship, extended family relationship, social
environment, and psychological distress. Items are
rated on a four-point scale, with higher scores indicating greater degrees of maladjustment. The total score
ranges from 0 – 135.
The BSI8 is a list of 53 symptoms of psychopathology, reduced from the 90-item symptom checklist. The
BSI has nine subscales: somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety,
hostility, phobic anxiety, paranoid ideation, and psychoticism. Norms are available for male and female
nonpatients and psychiatric outpatients.
Profile of Mood States (POMS)9 is a 65-item scale,
measuring 6 affective states: tension-anxiety, depression,
anger, vigor-activity, fatigue, and confusion. Each item is
rated on a 5-point scale, from 0 (not at all) to 4 (extremely).
Impact of Event Scale (IES)10 is a 15-item scale
measuring 2 dimensions that define posttraumatic
stress disorder: intrusive cognitions and avoidance or
blocking of thoughts and images related to the stress,
defined in this study as cancer.
Fear of recurrence was measured with five items
developed by one of the authors (A.B.K.), and rated
on a five-point Likert scale from ‘‘strongly agree’’ to
‘‘strongly disagree.’’ Internal consistency was very
good, with an alpha coefficient of 0.75.
In a series of face valid self-report items regarding
sexual problems, the patient was asked his/her state
in the year before diagnosis and currently, and then
whether he/she attributed this current state to having
had cancer. The items concern sexual interest, activity,
sexual attractiveness, acceptance by one’s partner, and
decreased interest in having a child.
The Body Image subscale of the Sexual Functioning
Inventory measures body image. Two items concerning
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satisfaction with the appearance of one’s penis and vagina
were removed as potentially offensive to this patient population. This left a 14-item scale for each gender.11
The Multidimensional Health Locus of Control Scale
is an 18-item scale that measures 3 dimensions of perceptions of control over one’s health: internal control, chance,
and powerful others, such as physicians.12
The Cognitive Restructuring Scale has 13 items designed to measure a patient’s ability to find positive aspects of the illness experience.13
The Family Functioning Scale was developed by one
of the authors (A.B.K.) from existing measures.14–17 The
measure was comprised of five dimensions: family cohesion, adaptability, emotional support, conflict, and communication.
Each of the five dimensions has six items. Items
in the emotional support subscale all were positively
worded and those in the conflict scale were worded
negatively. The remaining subscales had 50% of the
items framed positively and 50% of the items framed
negatively. The Family Function Scale total score and
four of the five subscales had very good to excellent
internal consistency (alpha coefficients: total score:
0.93; Family Cohesion: 0.82; Emotional Support: 0.86;
Conflict: 0.84; and Communication: 0.74). The Adaptation subscale had moderate internal consistency with
an alpha coefficient of 0.62.
The Conditioned Nausea, Vomiting, and Distress
Index was measured by asking whether any sights,
smells, or tastes of food or drink resulted in nausea,
vomiting, or distress within the last 6 months. The
intensity of response was rated on a scale of 0 to 10.6
The index was scored as 3 if vomiting was part of
the conditioned response, 2 if the response included
nausea but no vomiting, 1 if it included distress but no
vomiting or nausea, and zero if there was no distress,
nausea, or vomiting.
A Perceived Negative Socioeconomic Impact Index was created as the number of domains (family
income, education, and employment status) in which
the patient indicated that their current status differed
from what they believed it would have been without
having had cancer. The total score for the Perceived
Negative Socioeconomic Impact Index ranged from 0
to 3.6 Also collected was information regarding illness
and medical treatment factors, including type of leukemia (AML or acute lymphocytic leukemia [ALL]),
treatment received, the report of serious illness or
complications since finishing treatment, whether a recurrence had occurred after the initial treatment on
CALGB protocol, and the length of time elapsed from
last treatment to the interview.
Statistical Methods
A sample size of 200 leukemia survivors was required
for this study to detect a multiple correlation coeffi-
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Leukemia Survivors Predictors of Distress/Greenberg et al.
cient (R) of 0.40 at a 0.05 level of significance with 80%
power and 20 predictor variables.18
Pearson product moment correlations (r) were
calculated to examine the relationship between measures of adaptation, including the PAIS, BSI, POMS,
IES, Body Image subscale, fear of recurrence, and
Family Function. Regression methods were used to
determine whether sociodemographic, medical, psychologic, or social descriptors were significant predictors of adaptation. For ordered categoric dependent variables (categorized BSI and Conditioned Nausea, Vomiting, and Distress Index), ordinal logistic
regression was used. For other dependent variables,
such as PAIS, POMS, IES total scores, and the Body
Image subscale score, multiple regression methods
were used in these analyses.
All tests conducted were considered statistically
significant at the 0.05 level.
RESULTS
Patient Characteristics
The sociodemographic and medical characteristics of
the leukemia survivors interviewed in this study are
summarized in Table 1. With 38% of interviewed survivors having received treatment on CALGB 8525, the
median age at the interview was 41 years (median age
at diagnosis, 34 years). The median time since completion of CALGB protocol treatment was 5 years. Approximately 11% of patients had undergone BMT subsequent to their completion of initial protocol therapy.
Approximately 62% of survivors reported other serious illness since completion of leukemia treatment. Of
those 91 patients who specified diagnoses, 21% were most
likely related to treatment. For example, seven patients
reported hepatitis, two reported kidney compromise, two
had undergone hip surgery, one reported avascular necrosis of the hip, one reported transitory diabetes mellitus,
and one reported zoster infection.
Psychologic Distress
Approximately 14% of survivors had scores on the BSI
ú 1.5 standard deviation above the norm, a benchmark for psychiatric disorders. This level was twice as
many as would be expected in the normal population.
Mental health support had been sought by 21% of
patients after treatment. One patient had been hospitalized for depression. However, the majority of survivors scored within the normal range.
Approximately 2% of patients lived with a severe
anxiety regarding recurrence (mean score 4 or 5 of 5).
The fear of recurrence correlated significantly, with
the chance dimension on the Health Locus of Control
Scale (r Å 00.42; P õ 0.0001) and the Global Severity
Index (GSI) of the BSI (r Å 0.37; P õ 0.0001). In other
words, those patients most fearful of recurrence were
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1939
TABLE 1
Acute Leukemia Survivors Sample Characteristics
Total no. of leukemia survivors
Sociodemographic status at interview
Age (yrs)
Median
Range
Gender
Men
Women
Ethnicity
White
Black
Other
Marital status
Married
Single
Separated/divorced
Widowed
Employment
Full time
Part time
Unemployed/retired
Education
° 11th grade
High school graduate
Some college
College / advanced degree
Family income
õ $15,000
$15,000–29,999
$30,000–44,999
$45,000/
Medical history
Diagnosis
ALL
AML
Age at diagnosis (yrs)
Median
Range
Time after CALGB Treatment (yrs)
Median
Range
BMT after CALGB Treatment
Recurrence after treatment
Serious illness after treatment (not
necessarily due to leukemia
or its treatment)
206
41
21–90
49%
51%
93%
5%
2%
69%
16%
10%
4%
48%
15%
37%
12%
33%
28%
27%
15%
30%
24%
31%
23%
77%
34
12–73
5
1–17
11%
7%
62%
ALL: acute lymphocytic leukemia; AML: acute myelogenous leukemia; CALGB: Cancer and Leukemia
Group B; BMT: bone marrow transplantation.
those who believed neither they nor their physicians
had control over their health and those who had
greater overall psychologic distress.
Negative Effects Attributed to Leukemia
Patients attributed a number of negative life outcomes
to having had leukemia. Approximately 39% believed
that leukemia had effect on ¢ 1 dimensions of socioeconomic status: education, family income, and occu-
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CANCER November 15, 1997 / Volume 80 / Number 10
TABLE 2
Correlations of Major Measures of Adjustment and Family Functioninga
Scales
PAIS
BSI/GSI
POMS
IES
Body
Image
Fear of
recurrence
Family
Function
PAIS
BSI/GSI
POMS
IES
Body Image
Fear of recurrence
0.67
—
—
—
—
—
0.62
—
—
—
—
—
0.62
0.78
—
—
—
—
0.37
0.46
0.40
—
—
—
0.37
0.40
0.39
0.22
—
—
0.33
0.37
0.35
0.45
0.30
—
0.49
0.44
0.41
0.22
0.24
0.17
PAIS: Psychosocial Adjustment to Illness Scale; BSI/GSI: Brief Symptom Inventory/Global Severity Index; POMS: Profile of Mood States; IES: Impact of Event Scale.
a
Pearson Product Moment correlations significance: [r] r Å 0.17; P õ 0.05; r Å 0.22; P õ 0.01; r Å 0.24, P õ 0.001; All correlations ¢ 0.30, P õ 0.0001.
pation. Approximately 10% had less education at interview than they believed they would have attained if
they had not had leukemia; 6% had more education
than expected. Approximately 20% believed their family income was less than expected. Approximately 25%
were working less at the time of the interview than
expected if leukemia had not occurred and 56% had
health or life insurance problems. With regard to employment, 31% had some problem, 15% did not tell
their employer about the diagnosis, 7% were fired or
laid off, 10% did not receive a job offer, and 4% were
encouraged to leave their job.
Regarding sexual function, 26% attributed to cancer a decreased interest in having another child, and
33% blamed cancer for decreased sexual activity, 19%
for feeling unattractive, and 23% for a decreased interest in sex. Approximately 19% of men attributed a decreased ability to have an erection to cancer, and 9%
of women attributed pain with intercourse to having
had cancer. Only 8% felt less sexual acceptance and
9% less partner affection attributable to cancer. A decrement in sexual satisfaction attributed to cancer was
reported by 23%.
Conditioned Nausea and Vomiting
Approximately 71% of survivors retrospectively reported a history of treatment-related anticipatory distress, 40% anticipatory nausea, and 18% anticipatory
vomiting at the time of treatment. Reminders of cancer
treatment at the time of interview still provoked visceral distress, nausea, or vomiting in 51% of patients.
Interrelationship among the Measures of Adjustment
The intercorrelations of the major measures of adaptation and family functioning are presented in Table 2.
As anticipated, the PAIS, POMS, and BSI-GSI were significantly intercorrelated with each other (r 0.62 õ r
õ 0.78; P õ 0.0001). The Impact of Event Scale, fear
of recurrence, and Body Image scales also were sig-
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10-21-97 15:45:27
nificantly correlated with the PAIS, POMS, and BSI
(0.33 õ r õ 0.46; P õ 0.0001), but to a lesser degree
than these latter three measures with each other. As
an intervening variable, Family Functioning was expected to correlate less strongly with the other measures of adjustment, with its highest correlations being
with the BSI-GSI (r Å 0.44; P õ 0.0001) and the POMS
(r Å 0.41; P õ 0.0001).
Predictors of Adaptation
Sociodemographic, medical, and psychosocial predictors were examined for their ability to identify those
experiencing problems in adjustment. Table 3 presents the results of the multiple regression equations
for the PAIS, POMS, Impact of Event Scale, and Body
Image scale; the ordinal logistic regression equations
for the BSI-GSI categorized into Low, Moderate, and
High Distress; and the Conditioned Nausea, Vomiting,
and Distress Index, categorized as specified earlier.
Those reporting worse overall adjustment as measured
by the PAIS were those with less education (P õ 0.05),
those with other medical illnesses and complications
since treatment completion (P õ 0.001), and those
who had sought mental health treatment (P õ 0.05).
In terms of emotional state, women reported significantly greater distress than men, as measured by the
POMS (P õ 0.01), IES (P õ 0.05) and Body Image
subscale (P õ 0.01). Worse current family functioning
was highly significantly related to greater psychologic
distress as measured by the POMS (P õ 0.001). In the
ordinal logistic regression with the BSI-GSI categories,
those with other medical illnesses since their treatment who also were in more dysfunctional families
experienced greater psychologic distress than other
patients (P õ 0.05). Therefore, it was the combined
effect of both factors that placed survivors at greatest
risk of significant psychologic distress. Survivors retrospectively reporting anticipatory distress and vomiting
at the time of their chemotherapy treatment were
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Leukemia Survivors Predictors of Distress/Greenberg et al.
1941
TABLE 3
Significant Predictors of Leukemia Survivors’ Adjustment
Variables
Sociodemographic
Age
Female gender
Current marital status
Current education
Current income
Current employment
Part vs. full time
Unemp. vs. full time
Retired vs. full time
Medical
Time since Rx:
3–5 yrs vs. 1–2 yrs
6–10 yrs vs. 1–2 yrs
10/ yrs vs. 1–2 yrs
Relapse post-CALGB Protocol
BMT
Other medical illnesses
AML vs. ALL
Sick from chemo
Psychologic
Anticip. distress
Anticip. nausea
Anticip. vomiting
Believes health prof can
control health
Sought mental health Rx
Social
Family functioning
Family functioning 1 other
medical illness
R
R2
PAISa
BSIb
categorized
POMSa
IESa
Body
Imagea
Cond
N, V & Db
ns
ns
ns
00.94c,d
ns
00.05c,d
ns
ns
00.28d,e
ns
ns
13.92e
ns
ns
ns
ns
5.75c
ns
ns
ns
ns
0.32e
ns
ns
ns
0.03d,g
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
/16.13c,f
011.34f,g
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
8.22k
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
ns
06.05g,h
08.44c,h
07.73g,h
ns
ns
ns
ns
ns
ns
ns
ns
00.31g,i
ns
ns
ns
ns
01.37e,h
01.49e,h
01.77c,h
ns
01.25g,j
ns
ns
ns
4.47g
ns
ns
1.33c
ns
ns
ns
ns
ns
ns
ns
7.06g
ns
ns
ns
1.69e
0.92c
ns
ns
6.09c
ns
ns
ns
ns
ns
ns
ns
ns
0.50g
1.08c
NA
ns
22.16k
ns
ns
ns
NA
0.54
0.29
1.64c
0.62
0.38
ns
0.60
0.36
—
0.50
0.25
ns
0.51
0.26
ns
0.66
0.44
PAIS: Psychosocial Adjustment to Illness Scale; BSI: Brief Symptom Inventory; POMS: Profile of Mood States; IES: Impact of Event Scale; Cond. N, V, and D: conditioned nausea, vomiting, and distress; unemp.:
unemployed; ns; not significant; Rx: treatment; CALGB: Cancer and Leukemia Group B: BMT: bone marrow transplantation; AML: acute myelogenous leukemia; ALL: acute lymphatic leukemia; chemo: chemotherapy;
Anticip: anticipatory; prof: professionals; NA: not available; R: correlation coefficient.
a
Unstandardized coefficient from multiple regression model.
b
Unstandardized coefficient from ordinal logistic regression model.
c
P õ 0.05.
d
Negative signs indicate more distress with younger age or less education.
e
P õ 0.01.
f
Full employment correlated with greater distress scores on the Profile of Mood States.
g
P õ 0.10.
h
Negative signs indicate greater distress (Impact of Event Scale) or more conditioned vomiting when the time from treatment was shorter (1–2 years previous).
i
Those who had recurred after Cancer and Leukemia Group B treatment had less distress about body image.
j
Less conditioned nausea and vomiting was noted in those patients who underwent bone marrow transplantation.
k
P õ 0.001.
more likely to report greater current psychologic distress (BSI-GSI Distress Categories) (P õ 0.05). Anticipatory distress and anticipatory vomiting at the time
of their treatment, along with having sought treatment
for mental health problems (P õ 0.05) and completed
treatment more recently (P õ 0.05 – 0.01), were significant predictors of current conditioned nausea,
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vomiting, and distress in response to reminders of
their treatment (P õ 0.05 – 0.01). More recent completion of treatment also was significantly related to survivors having more intrusive and avoidant thoughts
about cancer (IES) (P õ 0.05 – 0.10). Contrary to expectation, being employed full time was related to greater
distress (POMS, P Å 0.05 – 0.10). As can be seen in
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CANCER November 15, 1997 / Volume 80 / Number 10
Table 3, many factors were not found to be significant
predictors of adjustment on many of the outcome
measures, including most of the medical characteristics, and a number of the important sociodemographic
variables, such as income and marital status. However,
across the regression equations involving the various
measures of adaptation, significant predictors accounted for approximately 25 – 44% of variance.
Logistic regression analysis also was used to identify significant medical and sociodemographic correlates of survivors’ perception that leukemia negatively
affected their socioeconomic status. Those who perceived a significant worsening in their socioeconomic
status due to leukemia (higher Perceived Negative Socioeconomic Index) were: diagnosed with AML (P õ
0.01), were younger (P Å 0.01), had less education prior
to diagnosis (P õ 0.05), were employed full time prior
to diagnosis (P õ 0.01), had a higher income prior to
diagnosis (P õ 0.05), and had completed treatment
within the past 2 years (P õ 0.10).
DISCUSSION
body image, had more intrusive thoughts or avoidant
behaviors related to cancer, and endorsed more descriptors of psychologic distress. Anxiety and depressive disorders are more common in women than
men in the general population,21 so female predominance of anxiety or depressive symptoms would be
expected in this sample as well. However, gender was
a less powerful predictor of psychiatric symptoms than
the other factors already discussed.
Continuing medical problems and troubled families interacted to increase the likelihood of psychologic
distress. Some of the iterated medical ailments were
conditions of persistent disability: diabetes, visual impairment, aseptic necrosis, graft versus host disease,
persistent or acute neurologic deficits, or heart disease. Repeated medical problems represented an obvious stress. However, the presence of medical illnesses
did not become a predictor of psychologic distress
unless family dysfunction also was noted. It also is
possible that more distressed survivors were more apt
to report serious medical illnesses and to be critical
of their family.
Although adult survivors of acute leukemia had a
higher level of distress than the normal population,
most appeared to have sound mental health. This result further supports data regarding adult survivors of
leukemia who did not undergo BMT1,2 and those who
did undergo BMT,3,4 and previous studies regarding
survivors of cancer.6,19 Most patients recover from the
trauma of the diagnosis and treatment without persistent symptoms of anxiety or depression. The challenges that these survivors must face do not prevent
many from finding an equilibrium in mood with few
psychiatric symptoms. Adjustment is more difficult
when other medical illnesses or complications add to
the burden.
Patients of younger age (most likely in their 20s
or 30s) and less educated patients (most likely with a
high school diploma or less) were more apt to have
greater psychologic distress an average of 5 years after
treatment. Those younger and less educated patients
also were more likely to attribute their current diminished socioeconomic status to leukemia. Younger age
also has been shown to be a predictor of anticipatory
nausea and vomiting, the mark of aversive conditioning to treatment.20
Closer attention should be paid to the psychologic
distress of patients in their 20s and 30s whose life has
been disrupted by leukemia, when fewer peers have
had serious illness. Those who were afflicted at a
younger age and those who had less education attributed their lesser status later in life to the impact of
leukemia. Those who were planning to work at manual
labor rather than desk jobs may have more difficulty.
Women were more distressed about changes in
Anticipatory Anxiety and Nausea
Our study also calls attention to anticipatory anxiety,
nausea, and vomiting (a treatment-related conditioned aversive response) as a risk factor for those patients with more persistent emotional difficulties. Survivors who reported anticipatory distress before infusion were more likely to have more anxiety and
depressive symptoms later.
In learning paradigms, nausea and vomiting are
particularly potent conditioning stimuli; little repetition of the lesson is required. Although no one looks
forward to chemotherapy, some patients more than
others develop significant anticipatory anxiety, nausea, or vomiting before infusion of the next treatment.
Those with anticipatory symptoms have longer postchemotherapy nausea with each treatment cycle.22,23
More chemotherapy treatments, more vomiting with
chemotherapy, and a history of motion sickness have
all been shown to increase the likelihood of anticipatory gut responses.24,25
In cancer patients, a classically conditioned model
can explain how anticipatory symptoms during treatment increase the likelihood that anxiety and gut responses will be provoked by treatment reminders
later.26,27 In this study, survivors reporting a history of
anticipatory vomiting were more likely to have recurrent intrusive thoughts and to avoid reminders of cancer. Those with persistent somatic responses were
more likely to have sought help from mental health
providers.
Some patients with anticipatory symptoms may
have had a greater constitutional tendency to anxiety.
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W: Cancer
Leukemia Survivors Predictors of Distress/Greenberg et al.
Jacobsen et al.23 showed that trait anxiety, expectations
that nausea would occur, and the patient’s attribution
of the symptom to chemotherapy predicted prechemotherapy anxiety. Morrow et al.20 also showed that
greater anxiety at the time of treatment predicted anticipatory nausea.
Because the reports of anticipatory distress and
nausea were retrospective in this study, those who
were still experiencing visceral distress with reminders
of treatment may have been biased by their current
symptoms in retrospectively reporting anticipatory
symptoms.
Posttraumatic Stress Disorder Model
Several researchers have suggested that the cancer
survivors’ psychiatric symptoms can be likened to
posttraumatic stress disorder (PTSD).28,29 The PTSD
model can be extended to explain the response of leukemia survivors. The core symptoms of PTSD include
repeated detailed replays of the traumatic event, the
tendency to avoid stimuli associated with the trauma,
and autonomic hyperarousal. Charney et al.30 describe
the neurobiologic dimensions of the disorder as 1) fear
conditioning (anxiety, flashbacks, hyperarousal when
reminded, and numbing to general stimuli); 2) failure
of extinction (failure of reduction in the conditioned
response); and 3) sensitization (increased magnitude
of response to a different intense stimulus). Conditioned anxiety, which can be suppressed by benzodiazepines, represents a subcortical, virtually permanent
memory that can be reawakened with the repetition
of the trauma.
In cancer patients, anticipatory anxiety during
treatment is the sign of fear conditioning in progress,
the first sign to predict persistent anxiety later. Conditioned visceral responses, intrusive thoughts, and
avoidant behavior to reminders of treatment indicate
that the memory of treatment has not been extinguished. Extinction increases with time from the last
reminder. Necessary reminders such as follow-up visits to the doctor are likely to rekindle arousal.
Clinical Implications
Most survivors of acute leukemia weather the treatment and recover without significant psychiatric
symptoms. The importance of the syndrome of anticipatory anxiety and nausea is that it may be a marker
for a group of survivors who are more likely to develop
syndromes of anxiety or depression. The best way to
minimize conditioned nausea is to maximize antiemetic treatment, and more potent agents now are
available. The best way to reduce procedure-related
anticipatory anxiety is to prepare patients for procedures and to give adequate analgesia. Early attention
to those patients who develop conditioned anticipa-
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1943
tory anxiety may reduce the likelihood of persistent
anxiety or secondary depression in survivors. Benzodiazepines 31 as well as behavioral anti-anxiety techniques26,27 have reduced anticipatory and posttreatment nausea in patients as they receive chemotherapy.
In this study, data were acquired retrospectively about
anticipatory distress, nausea, and vomiting with treatment. Documentation of these symptoms prospectively, in the modern environment of anti-emetic
treatment would strengthen the thesis.
In addition to anticipatory anxiety syndromes,
there should be greater suspicion of psychiatric distress, particularly anxiety and depressive syndromes,
in leukemia survivors who are younger, less educated
at the time of diagnosis, and those with chronic medical problems that further tax family function. Targeted
occupational/training support for those patients who
are less educated, family support for those with persistent medical problems, and psychiatric treatment for
those who develop major depressive disorder, make
practical sense.
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