Review article
Quality of life after allogeneic hematopoietic cell transplantation
Joseph Pidala,
1,2
Claudio Anasetti,
1,2
and Heather Jim
2,3
1
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL;
2
Oncologic Sciences, University of South Florida, Tampa; and
3
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL
High-dose therapy with allogeneic hema-
topoietic cell transplantation (HCT) offers
effective control and potential cure of
hematopoietic malignancies, but with the
cost of associated morbidity that in-
cludes adverse effects on quality of life
(QOL). A growing body of literature has
characterized this impact. Longitudinal
studies suggest early moderate impair-
ments that largely return to pretransplan-
tation levels by day 100; the majority of
studies suggest that greater than 60% of
patients report good to excellent QOL in
years 1 to 4 after HCT. Comparisons of
allogeneic HCT with autologous HCT and
standard-dose chemotherapy suggest im-
pairments in QOL and a different trajec-
tory of recovery in allogeneic HCT, but
these conclusions are limited by con-
founding variables. Cross-sectional stud-
ies suggest larger and more persistent
decrements in QOL in comparison with
matched noncancer controls and popula-
tion normative data. Acute and chronic
graft-versus-host disease (GVHD) are sig-
nificant threats to QOL. Behavioral inter-
ventions show promise to maintain or
improve quality of life after allogeneic
HCT. The review concludes with recom-
mendations to investigators and clini-
cians as the state of this research ad-
vances. (Blood. 2009;114:7-19)
Introduction
Quality of life (QOL) is a dynamic, multifaceted concept related to
physical, cognitive, emotional, and social functioning and well-
being. Issues related to QOL are routinely cited by cancer survivors
as among their greatest concerns.
1
QOL is an especially important
consideration in the counseling, implementation, and posttreatment
management of arduous treatments for life-threatening conditions,
such as allogeneic hematopoietic cell transplantation (HCT).
Although potentially lifesaving, allogeneic HCT carries an atten-
dant risk of significant acute complications, late effects including
chronic graft-versus-host disease (GVHD), organ toxicity, osteopo-
rosis, infections, cataracts, secondary cancers, and infertility, as
well as decrements in QOL.
2-5
A growing literature has described
the impact of HCT on QOL, but is characterized by heterogeneity
in study design, patient population, comparator groups, assessment
instruments, time points examined, and conclusions reached.
A cohesive overview is needed to integrate these studies and
describe the clinical and research implications of findings.
The aim of the current review is to synthesize and critically
evaluate the current literature on QOL after allogeneic HCT in
adults. We start by addressing issues in the assessment of QOL in
HCT. We also examine the concept of clinically significant change
in QOL.We then summarize studies in a way we believe to be most
relevant to clinical practice, including longitudinal change in QOL
in allogeneic HCT and comparisons of QOL in allogeneic HCT
with autologous HCT, standard-dose chemotherapy, healthy matched
comparators, and population norms. An examination of GVHD,
reduced-intensity conditioning regimens (RICs), and other predic-
tors of QOL follows. Patient-reported benefits of HCT and
behavioral interventions to maintain or improve QOL are then
described. We conclude with a discussion and recommendations to
researchers and clinicians.
Methods
A Medline search was conducted using MeSH terms “quality of
life” or “health related quality of life” and “bone marrow transplan-
tation” or “hematopoietic stem cell transplantation.” Further searches
were conducted based on related references identified in Medline
and examination of references cited in selected articles. Criteria for
selected articles were (1) HCT for hematologic malignancies,
(2) sample of adults at time of assessment, (3) inclusion of patients
who underwent allogeneic HCT, and (4) use of at least one
quantitative multi-item measure of QOL. Excluded studies were
those exclusively focused on pediatric populations, only autolo-
gous HCT, available only in non-English languages, or otherwise
not relevant.
Assessment of QOL in HCT
Although there is recognition of the importance of standardized
assessment of QOL across clinical trials,
6
there is currently no
consensus regarding which measure should be used. Instead, the
HCT literature encompasses a variety of QOL measures, including
broad measures of QOL in healthy and patient populations,
measures of cancer-specific QOL, HCT-specific QOL, and GVHD-
specific side effects (Table 1). General measures of QOL have the
advantage of applicability for both patients who underwent HCT
and comparison groups, but may be less sensitive to side effects of
transplantation, including acute and chronic GVHD, than HCT-
specific measures.
7,8
Thus, investigators may wish to supplement a
general QOL measure with a HCT- or GVHD-specific measure to
adequately capture QOL.
There is also significant heterogeneity in the content of QOL
measures, as seen in Table 1. Even measures assessing similar
domains of QOL may differ in content. In a comparison of the
Submitted October 4, 2008; accepted March 24, 2009. Prepublished online
as Blood First Edition paper, March 31, 2009; DOI 10.1182/blood-2008-10-
182592.
© 2009 by The American Society of Hematology
7BLOOD, 2 JULY 2009


VOLUME 114, NUMBER 1

T
a
b
l
e
1
.
Q
u
a
n
t
i
t
a
t
i
v
e
,
m
u
l
t
i
-
i
t
e
m
m
e
a
s
u
r
e
s
c
o
m
m
o
n
l
y
u
s
e
d
t
o
a
s
s
e
s
s
Q
O
L
i
n
H
C
T
p
a
t
i
e
n
t
s
M
e
a
s
u
r
e
n
a
m
e
A
b
b
r
e
v
i
a
t
i
o
n
P
u
r
p
o
s
e
D
o
m
a
i
n
s
a
s
s
e
s
s
e
d
N
o
.
o
f
i
t
e
m
s
V
a
l
i
d
a
t
i
o
n
s
a
m
p
l
e
(
s
)
R
e
l
i
a
b
i
l
i
t
y
C
i
t
y
o
f
H
o
p
e
/
S
t
a
n
f
o
r
d
L
o
n
g
t
e
r
m
B
M
T
S
u
r
v
i
v
o
r
I
n
d
e
x
8
4
B
M
T
-
S
S
,
C
O
H
-
Q
O
L
H
C
T
-
s
p
e
c
i
fi
c
Q
O
L
S
u
b
s
c
a
l
e
s
:
P
r
o
d
u
c
t
i
v
e
a
c
t
i
v
i
t
y
a
n
d
f
u
n
c
t
i
o
n
i
n
g
,
h
e
a
l
t
h
s
t
a
t
u
s
a
n
d
t
r
e
a
t
m
e
n
t
-
r
e
l
a
t
e
d
p
h
y
s
i
c
a
l
s
y
m
p
t
o
m
s
,
q
u
a
l
i
t
a
t
i
v
e
a
s
p
e
c
t
s
o
f
d
a
i
l
y
l
i
f
e
3
3
i
t
e
m
s
a
s
s
e
s
s
e
d
v
i
a
i
n
t
e
r
v
i
e
w
H
C
T
p
a
t
i
e
n
t
s
—
C
a
n
c
e
r
R
e
h
a
b
i
l
i
t
a
t
i
o
n
E
v
a
l
u
a
t
i
o
n
S
y
s
t
e
m
–
S
h
o
r
t
F
o
r
m
8
5
C
A
R
E
S
-
S
F
,
C
I
P
G
e
n
e
r
a
l
m
e
a
s
u
r
e
o
f
Q
O
L
i
n
c
a
n
c
e
r
S
u
b
s
c
a
l
e
s
:
P
h
y
s
i
c
a
l
,
p
s
y
c
h
o
s
o
c
i
a
l
,
s
e
x
u
a
l
,
m
a
r
i
t
a
l
,
m
e
d
i
c
a
l
i
n
t
e
r
a
c
t
i
o
n
;
G
l
o
b
a
l
C
A
R
E
S
1
3
9
i
t
e
m
s
i
n
L
i
k
e
r
t
s
c
a
l
e
f
o
r
m
a
t
P
a
t
i
e
n
t
s
w
i
t
h
h
e
t
e
r
o
g
e
n
e
o
u
s
c
a
n
c
e
r
d
i
a
g
n
o
s
e
s
T
e
s
t
-
r
e
t
e
s
t
:
.
8
2
-
.
9
1
8
5
E
u
r
o
p
e
a
n
O
r
g
a
n
i
z
a
t
i
o
n
f
o
r
t
h
e
R
e
s
e
a
r
c
h
a
n
d
T
r
e
a
t
m
e
n
t
o
f
C
a
n
c
e
r
Q
u
a
l
i
t
y
o
f
L
i
f
e
Q
u
e
s
t
i
o
n
n
a
i
r
e
8
6
E
O
R
T
C
Q
L
Q
-
C
3
0
G
e
n
e
r
a
l
m
e
a
s
u
r
e
o
f
Q
O
L
i
n
c
a
n
c
e
r
F
u
n
c
t
i
o
n
i
n
g
s
c
a
l
e
s
:
p
h
y
s
i
c
a
l
,
s
o
c
i
a
l
,
r
o
l
e
,
c
o
g
n
i
t
i
v
e
,
e
m
o
t
i
o
n
a
l
;
S
y
m
p
t
o
m
s
c
a
l
e
s
:
f
a
t
i
g
u
e
,
p
a
i
n
,
n
a
u
s
e
a
/
v
o
m
i
t
i
n
g
;
G
l
o
b
a
l
h
e
a
l
t
h
/
Q
O
L
s
c
a
l
e
3
0
i
t
e
m
s
i
n
y
e
s
/
n
o
o
r
L
i
k
e
r
t
s
c
a
l
e
f
o
r
m
a
t
N
o
n
r
e
s
e
c
t
a
b
l
e
l
u
n
g
c
a
n
c
e
r
C
r
o
n
b
a
c
h
a
l
p
h
a
:
.
5
4
-
.
8
6
8
6
E
u
r
o
p
e
a
n
O
r
g
a
n
i
z
a
t
i
o
n
f
o
r
t
h
e
R
e
s
e
a
r
c
h
a
n
d
T
r
e
a
t
m
e
n
t
o
f
C
a
n
c
e
r
Q
u
a
l
i
t
y
o
f
L
i
f
e
Q
u
e
s
t
i
o
n
n
a
i
r
e
–
L
e
u
k
e
m
i
a
m
o
d
u
l
e
3
5
,
8
7
E
O
R
T
C
Q
L
Q
-
L
E
U
,
E
O
R
T
C
Q
L
Q
-
L
E
U
-
B
M
T
L
e
u
k
e
m
i
a
-
s
p
e
c
i
fi
c
Q
O
L
S
u
b
s
c
a
l
e
s
:
G
V
H
D
,
i
n
f
e
c
t
i
o
n
3
2
i
t
e
m
s
i
n
L
i
k
e
r
t
s
c
a
l
e
f
o
r
m
a
t
A
c
u
t
e
m
y
e
l
o
g
e
n
o
u
s
l
e
u
k
e
m
i
a
C
r
o
n
b
a
c
h
a
l
p
h
a
:
.
7
1
-
.
7
9
8
7
F
u
n
c
t
i
o
n
a
l
A
s
s
e
s
s
m
e
n
t
o
f
C
a
n
c
e
r
T
h
e
r
a
p
y
–
G
e
n
e
r
a
l
8
8
F
A
C
T
-
G
G
e
n
e
r
a
l
m
e
a
s
u
r
e
o
f
Q
O
L
i
n
c
a
n
c
e
r
S
u
b
s
c
a
l
e
s
:
p
h
y
s
i
c
a
l
,
f
u
n
c
t
i
o
n
a
l
,
s
o
c
i
a
l
,
e
m
o
t
i
o
n
a
l
,
r
e
l
a
t
i
o
n
s
h
i
p
w
i
t
h
d
o
c
t
o
r
;
T
o
t
a
l
s
c
o
r
e
2
8
i
t
e
m
s
i
n
L
i
k
e
r
t
s
c
a
l
e
f
o
r
m
a
t
P
a
t
i
e
n
t
s
w
i
t
h
h
e
t
e
r
o
g
e
n
e
o
u
s
c
a
n
c
e
r
d
i
a
g
n
o
s
e
s
C
r
o
n
b
a
c
h
a
l
p
h
a
:
.
6
5
-
.
8
9
8
8
;
3
-
7
d
t
e
s
t
-
r
e
t
e
s
t
:
.
8
2
-
.
9
2
8
8
F
u
n
c
t
i
o
n
a
l
A
s
s
e
s
s
m
e
n
t
o
f
C
a
n
c
e
r
T
h
e
r
a
p
y
–
B
o
n
e
M
a
r
r
o
w
T
r
a
n
s
p
l
a
n
t
M
o
d
u
l
e
3
4
F
A
C
T
-
B
M
T
H
C
T
-
s
p
e
c
i
fi
c
Q
O
L
F
A
C
T
-
G
;
B
M
T
s
u
b
s
c
a
l
e
(
B
M
T
S
)
;
T
r
i
a
l
O
u
t
c
o
m
e
I
n
d
e
x
(
T
O
I
)
:
s
u
m
o
f
p
h
y
s
i
c
a
l
,
f
u
n
c
t
i
o
n
a
l
,
B
M
T
S
s
u
b
s
c
a
l
e
s
4
7
i
t
e
m
s
i
n
L
i
k
e
r
t
s
c
a
l
e
f
o
r
m
a
t
H
C
T
p
a
t
i
e
n
t
s
C
r
o
n
b
a
c
h
a
l
p
h
a
a
t
d
i
s
c
h
a
r
g
e
:
.
5
2
-
.
8
5
3
4
F
u
n
c
t
i
o
n
a
l
L
i
v
i
n
g
I
n
d
e
x
–
C
a
n
c
e
r
8
9
F
L
I
C
G
e
n
e
r
a
l
m
e
a
s
u
r
e
o
f
Q
O
L
i
n
c
a
n
c
e
r
S
u
b
s
c
a
l
e
s
:
p
h
y
s
i
c
a
l
,
p
s
y
c
h
o
l
o
g
i
c
,
s
o
c
i
a
l
,
c
u
r
r
e
n
t
w
e
l
l
-
b
e
i
n
g
,
g
a
s
t
r
o
i
n
t
e
s
t
i
n
a
l
s
y
m
p
t
o
m
s
;
T
o
t
a
l
s
c
o
r
e
2
2
i
t
e
m
s
i
n
v
i
s
u
a
l
a
n
a
l
o
g
u
e
s
c
a
l
e
P
a
t
i
e
n
t
s
w
i
t
h
h
e
t
e
r
o
g
e
n
e
o
u
s
c
a
n
c
e
r
d
i
a
g
n
o
s
e
s
C
r
o
n
b
a
c
h
a
l
p
h
a
:
.
6
5
-
.
8
7
8
9
c
G
V
H
D
S
y
m
p
t
o
m
S
c
a
l
e
7
—
M
e
a
s
u
r
e
o
f
s
y
m
p
t
o
m
s
o
f
c
G
V
H
D
S
u
b
s
c
a
l
e
s
:
e
n
e
r
g
y
,
s
k
i
n
,
n
u
t
r
i
t
i
o
n
,
l
u
n
g
,
p
s
y
c
h
o
l
o
g
i
c
,
e
y
e
,
m
o
u
t
h
;
O
v
e
r
a
l
l
3
0
i
t
e
m
s
i
n
L
i
k
e
r
t
s
c
a
l
e
f
o
r
m
a
t
H
C
T
p
a
t
i
e
n
t
s
C
r
o
n
b
a
c
h
a
l
p
h
a
:
.
7
9
-
.
8
5
7
;
T
e
s
t
-
r
e
t
e
s
t
:
.
2
8
-
.
9
3
7
M
e
d
i
c
a
l
O
u
t
c
o
m
e
s
S
t
u
d
y
S
h
o
r
t
F
o
r
m
–
3
6
9
0
,
9
1
S
F
-
3
6
G
e
n
e
r
a
l
m
e
a
s
u
r
e
o
f
Q
O
L
i
n
h
e
a
l
t
h
y
a
n
d
p
a
t
i
e
n
t
p
o
p
u
l
a
t
i
o
n
s
S
u
b
s
c
a
l
e
s
:
p
h
y
s
i
c
a
l
f
u
n
c
t
i
o
n
i
n
g
,
r
o
l
e
–
p
h
y
s
i
c
a
l
,
b
o
d
i
l
y
p
a
i
n
,
g
e
n
e
r
a
l
h
e
a
l
t
h
,
v
i
t
a
l
i
t
y
,
s
o
c
i
a
l
f
u
n
c
t
i
o
n
i
n
g
,
r
o
l
e
–
e
m
o
t
i
o
n
a
l
,
m
e
n
t
a
l
h
e
a
l
t
h
;
C
o
m
p
o
s
i
t
e
s
c
o
r
e
s
:
p
h
y
s
i
c
a
l
,
m
e
n
t
a
l
3
6
i
t
e
m
s
i
n
y
e
s
/
n
o
o
r
L
i
k
e
r
t
s
c
a
l
e
f
o
r
m
a
t
G
e
n
e
r
a
l
U
S
p
o
p
u
l
a
t
i
o
n
,
c
a
r
d
i
a
c
p
a
t
i
e
n
t
s
,
c
h
r
o
n
i
c
p
a
i
n
,
d
i
a
b
e
t
e
s
,
d
e
p
r
e
s
s
i
o
n
C
r
o
n
b
a
c
h
a
l
p
h
a
:
.
6
3
-
.
9
4
9
0
,
9
1
M
e
d
i
c
a
l
O
u
t
c
o
m
e
s
S
t
u
d
y
S
h
o
r
t
F
o
r
m
–
1
2
9
2
S
F
-
1
2
G
e
n
e
r
a
l
m
e
a
s
u
r
e
o
f
Q
O
L
i
n
h
e
a
l
t
h
y
a
n
d
p
a
t
i
e
n
t
p
o
p
u
l
a
t
i
o
n
s
C
o
m
p
o
s
i
t
e
s
c
o
r
e
s
:
p
h
y
s
i
c
a
l
,
m
e
n
t
a
l
1
2
i
t
e
m
s
i
n
y
e
s
/
n
o
o
r
L
i
k
e
r
t
s
c
a
l
e
f
o
r
m
a
t
G
e
n
e
r
a
l
U
S
p
o
p
u
l
a
t
i
o
n
T
w
o
w
e
e
k
t
e
s
t
-
r
e
t
e
s
t
:
.
7
6
,
.
8
9
9
2
N
o
t
t
i
n
g
h
a
m
H
e
a
l
t
h
P
r
o
fi
l
e
9
3
N
H
P
G
e
n
e
r
a
l
m
e
a
s
u
r
e
o
f
Q
O
L
i
n
h
e
a
l
t
h
y
a
n
d
p
a
t
i
e
n
t
p
o
p
u
l
a
t
i
o
n
s
S
u
b
s
c
a
l
e
s
:
e
n
e
r
g
y
l
e
v
e
l
,
p
a
i
n
,
e
m
o
t
i
o
n
a
l
r
e
a
c
t
i
o
n
,
s
l
e
e
p
,
s
o
c
i
a
l
i
s
o
l
a
t
i
o
n
,
p
h
y
s
i
c
a
l
a
b
i
l
i
t
i
e
s
3
8
i
t
e
m
s
i
n
y
e
s
/
n
o
f
o
r
m
a
t
M
e
d
i
c
a
l
p
a
t
i
e
n
t
s
,
h
e
a
l
t
h
y
i
n
d
i
v
i
d
u
a
l
s
F
o
u
r
w
e
e
k
t
e
s
t
-
r
e
t
e
s
t
:
.
7
7
-
.
8
5
9
3
Q
u
a
l
i
t
y
o
f
L
i
f
e
I
n
d
e
x
9
4
Q
L
I
G
e
n
e
r
a
l
m
e
a
s
u
r
e
o
f
Q
O
L
i
n
p
a
t
i
e
n
t
p
o
p
u
l
a
t
i
o
n
s
T
o
t
a
l
s
c
o
r
e
5
i
t
e
m
s
i
n
L
i
k
e
r
t
s
c
a
l
e
f
o
r
m
a
t
a
s
s
e
s
s
e
d
b
y
p
h
y
s
i
c
i
a
n
M
e
d
i
c
a
l
p
a
t
i
e
n
t
s
C
r
o
n
b
a
c
h
a
l
p
h
a
:
.
7
8
9
4
8 PIDALA et al BLOOD, 2 JULY 2009


VOLUME 114, NUMBER 1