Post-transplant events
Characteristics and correlates of cognitive functioning following bone
marrow transplantation
M Booth-Jones
1,2
, PB Jacobsen
1,2
, S Ransom
1,2
and E Soety
3
1
University of South Florida, Tampa, FL, USA;
2
H Lee Moffitt Cancer Center, Psychosocial and Palliative Care, Tampa, FL, USA;
and
3
Baylor College of Medicine, Houston, TX, USA
Summary:
Patients who undergo bone marrow transplantation
(BMT) often report cognitive problems following treat-
ment.This study used cognitive tests and a self-report
measure of subjective cognitive complaints to determine
(1) the rate of objective cognitive impairment in a sample
of 65 BMT patients, and (2) the correspondence of
patients’ cognitive complaints to their actual cognitive
performance.At 6 months following BMT, patients were
assessed in seven cognitive domains – attention, verbal
learning, verbal memory, visual memory, simple executive
function, complex executive function, and psychomotor
speed.Cognitive complaints were likewise assessed.In all,
51% had at least mild impairment (
1 standard deviation
(s.d.) below published norms) in one or more cognitive
domains, with 28% demonstrating moderate-to-severe
impairment (
2 s.d.). Older patients and patients with
lower IQ were more likely to score in the impaired range
on objective cognitive tests, with males and the less
educated showing trends toward scores in the impaired
range.Younger patients made significantly more cognitive
complaints.Total cognitive complaints were unrelated to
average cognitive performance, and complaints in specific
cognitive domains were largely unrelated to objective
performance on corresponding domains.Findings suggest
that patients who complain about their cognitive perfor-
mance following BMT differ from those who experience
actual deficits.
Bone Marrow Transplantation (2005) 36, 695–702.
doi:10.1038/sj.bmt.1705108; published online 8 August 2005
Keywords: neuropsychology; cognitive deficits; cognitive
complaints
Allogeneic and autologous methods of blood and bone
marrow transplantation (BMT) have become standard
treatments for many forms of cancer. According to the
International Bone Marrow Transplant Registry (2002),
more than 50 000 cancer patients worldwide undergo either
allogeneic or autologous stem cell transplant each year,
and experts expect a 10–15% increase in the number of
blood and marrow transplants performed annually.
1
The
National Marrow Donor Program, which tracks allogeneic
transplants, reported more than 2100 transplants of this
type for the year 2002 in the United States.
2
As more cancer patients undergo stem cell transplant-
ation or BMT and as they survive for longer periods of
time, concerns have grown about the quality of life of BMT
survivors.
3
Clinical reports suggest that problems with
cognitive functioning – including problems with memory,
concentration, and mental processing speed – are a
common and important quality of life concern for BMT
survivors.
4,5
Difficulties with cognitive functioning can pose
significant problems for patients as they attempt to resume
their lives following treatment. Evidence regarding cogni-
tive problems in BMT survivors is limited, however, since
few studies have assessed both cognitive functioning and
self-reports of cognitive complaints in the post transplant
period.
In one of the first studies to address this issue, Meyers
et al
4
identified general cognitive impairment using a brief
cognitive screening measure (Mattis Dementia Rating
Scale
6
) in 10% of a BMT sample approximately 8 months
post transplant with the most frequently observed impair-
ment in executive function (29%). Transplant type was
unrelated to cognitive impairment in this study.
More recently, van Dam et al
5
assessed cognitive
function in breast cancer patients treated with high-dose
chemotherapy with stem cell rescue or standard-dose
chemotherapy, and used a local therapy-only group as a
control. Approximately 19 months after treatment, patients
completed a cognitive battery with impairment defined as
2 standard deviations (s.d.) lower than the mean of the
control group on at least three cognitive tests. Cognitive
impairment was observed in 32% of the high-dose group,
17% of the standard-dose group, and 9% of the com-
parison group, with the most common impairments on
measures of attention/concentration, mental flexibility,
information processing speed, visual memory, and motor
function. Furthermore, neurophysiological evidence for
cognitive dysfunction in this group was identified.
7
Harder et al
8
assessed cognitive function in cancer
patients 2–7years post transplant. With impairment
defined as 2 s.d.’s below published norms, 60% were
Received 1 February 2005; accepted 21 June 2005; published online
8 August 2005
Correspondence: Dr M Booth-Jones, H Lee Moffitt Cancer Center,
Psychosocial and Palliative Care, MRC-PSY, 12902 Magnolia Dr,
Tampa, FL 33612-9497, USA; E-mail: jonesm@moffitt.usf.edu
Bone Marrow Transplantation (2005) 36, 695–702
& 2005 Nature Publishing Group All rights reserved 0268-3369/05 $30.00
www.nature.com/bmt

impaired on at least one test with the most frequent
impairments observed on measures of information proces-
sing speed (32.5%), attention and executive function
(23.1%), and visual memory (20.5%). Type of transplant
was unrelated to cognitive impairment.
Most recently, Syrjala et al
9
used a longitudinal design to
examine cognitive changes in patients receiving allogeneic
stem cell transplantation. Compared with pre-transplant
baselines, decreases in processing speed, attention, learning,
verbal memory, motor functioning, and visuomotor per-
formance 80 days post transplant were observed. With the
exceptions of motor dexterity and grip strength, most
deficits improved to some extent at the 1-year assessment;
however, 74% continued to score at least 1 s.d. below
published norms on at least one test. Previous chemother-
apy was related to impairment in cognitive functioning.
Two of the studies reviewed above used interview-based
measures to evaluate patients’ complaints about their
cognitive functioning. van Dam et al
5
found that compared
to the local therapy comparison group, patients treated
with high-dose chemotherapy reported significantly
(Po0.05) more problems with concentration, memory,
and thinking. The prevalence of complaints about cognitive
functioning in the high-dose chemotherapy group ranged
from 38% for concentration to 12% for language. The
relationship between cognitive complaints and neuro-
psychological evidence of cognitive impairment was not
significant.
Harder et al
8
found that 62.5% of patients complained of
problems with memory, and 50% of patients complained of
problems with attention. Complaints in other cognitive
domains were not assessed. This same study also found a
significant (Po0.05) relationship between patients’ self-
reports of cognitive complaints and neuropsychological
evidence of cognitive impairment.
Both van Dam et al
5
and Harder et al
8
examined the
relationship of cognitive impairment and cognitive com-
plaints to various quality of life domains. van Dam et al
found that greater cognitive impairment was related to
greater depression (Po0.05), and that more cognitive
complaints were related to greater depression, anxiety,
and poorer emotional functioning (Po0.05). Harder et al
8
found that greater cognitive impairment was related to
poorer physical and social functioning, as well as greater
emotional distress, anxiety, and fatigue (Po0.05). In
addition, cognitive complaints were associated with greater
fatigue (Po0.05).
Although these and other studies provide welcome clues
to the nature of cognitive problems following BMT, the
number of studies that have examined these issues remains
small and conclusions that may be drawn from these
studies remain limited. Even so, evidence suggests that
transplant recipients are at increased risk for cognitive
problems relative to patients treated without chemother-
apy
5
and the general population,
8
and that poorer cognitive
functioning is associated with poorer quality of life.
5,8
On
the other hand, the relationship of subjective complaints to
objective evidence of cognitive impairment remains unclear,
with two major studies differing as to their conclusions.
The present study sought to add to this growing
literature by evaluating cognitive functioning and quality
of life in a sample of BMT recipients approximately 6
months post-discharge. The study employed an extensive
battery of well-normed cognitive measures that assessed
a range of cognitive domains, a self-report measure of
complaints in various cognitive domains, and standardized
measures of both physical and mental aspects of quality of
life. The specific objectives of this study were three-fold:
(1) to determine the prevalence and characteristics of
subjective reports of cognitive complaints and objective
evidence of cognitive impairment following BMT; (2) to
examine the relationship between cognitive complaints and
cognitive impairment following BMT; and (3) to determine
the relationship of cognitive complaints and cognitive
impairment to quality of life following BMT. Although
the primary purpose of this study was exploratory, we
hypothesized that both cognitive complaints and actual
cognitive impairment would be related to deficits in post-
BMT quality of life.
Patients and methods
Patients
Participants were cancer patients who had completed
autologous or allogeneic BMT as part of their treatment
at the H Lee Moffitt Cancer Center in Tampa, FL, USA
between September 1997and July 1999. To be eligible for
the current study, these patients had to: (1) be between 18
and 65 years of age; (2) be able to speak and read English;
(3) have completed at least 8 years of formal education;
(4) have no clinical evidence of disease progression or
recurrence at the most recent follow-up visit; and (5) be
approximately 6 months post-discharge from BMT.
Of 100 BMT recipients meeting eligibility criteria, seven
patients could not be contacted, 16 refused to participate,
seven did not complete cognitive testing, but did complete
self-report questionnaires, and five completed cognitive
testing but did not complete self-report questionnaires.
Complete cognitive and self-report data were obtained
from 65 of 100 BMT recipients (65%). Analyses comparing
participants who provided complete data (n¼ 65) with
eligible nonparticipants (n¼ 35) indicated that there were
no significant differences (Po0.05) between the groups in
terms of gender, age, ethnicity, education, marital status,
employment status, or type of transplant. However, there
was a significant (Po0.05) group difference in cancer
diagnosis, with participants more likely than nonpartici-
pants to be diagnosed with breast cancer (67% vs 39%).
Study participants ranged in age from 23 to 63 years
(M¼ 47, s.d.¼ 9). The majority of participants were female
(78%), Caucasian (92%), currently married (62.5%) and
were educated beyond high school (67%). Average educa-
tion level was 14.1 years (s.d.¼ 2.6, range 8–20 years). In
all, 30% were currently employed, 41% were on leave, and
the remaining 29% were not currently employed. In total,
81% of the sample underwent autologous transplantation
and 19% underwent allogeneic transplantation. The
majority of patients (67%) were diagnosed with breast
cancer, followed by leukemia (13%), lymphoma (11%),
and multiple myeloma (9%). Participants were approxi-
Cognitive functioning following BMT
M Booth-Jones et al
696
Bone Marrow Transplantation