A Molassiotis

Akira Akabayashi

C Fausel

F Baker

Hiroe Kikuchi

HN Brown

J Larsen

K Yokoyama

Kazuhiro Yoshiuchi

Keiki Kumano

KL Syrjala

MA Andrykowski

Maki Hachizuka

Mineo Kurokawa

MJ Hjermstad

Noriyuki Sakamoto

S Larson

S Leigh

Shuji Inada

SM Johnson Vickberg

T Sasaki

Tsuyoshi Takahashi

Wataru Fukuo

Yasuhito Nannya

Yoshiyuki Takimoto

BioPsychoSocial Medicine

English

PubMed

Springer - Publisher Connector

BioMed CentralBioPsychoSocial Medicine
ssOpen AcceShort report
Comparison of temporal changes in psychological distress after 
hematopoietic stem cell transplantation among the underlying 
diseases of Japanese adult patients
Wataru Fukuo1, Kazuhiro Yoshiuchi*1, Yoshiyuki Takimoto1, 
Noriyuki Sakamoto1, Hiroe Kikuchi1, Maki Hachizuka1, Shuji Inada1, 
Yasuhito Nannya2, Keiki Kumano3, Tsuyoshi Takahashi2, Mineo Kurokawa2,3 
and Akira Akabayashi1
Address: 1Department of Stress Sciences and Psychosomatic Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan, 
2Department of Hematology/Oncology, the University of Tokyo, Tokyo, Japan and 3Department of Cell Therapy and Transplantation Medicine, 
the University of Tokyo, Tokyo, Japan
Email: Wataru Fukuo - fukuow-tky@umin.ac.jp; Kazuhiro Yoshiuchi* - kyoshiuc-tky@umin.ac.jp; Yoshiyuki Takimoto - taki-tky@umin.ac.jp; 
Noriyuki Sakamoto - nomimi-tky@umin.ac.jp; Hiroe Kikuchi - kikuchih-tky@umin.ac.jp; Maki Hachizuka - hachimaki-tky@umin.ac.jp; 
Shuji Inada - shiinada-tky@umin.ac.jp; Yasuhito Nannya - ynanya-tky@umin.net; Keiki Kumano - kumano-tky@umin.ac.jp; 
Tsuyoshi Takahashi - tsu-tky@umin.ac.jp; Mineo Kurokawa - kurokawa-tky@umin.ac.jp; Akira Akabayashi - akirasan-tky@umin.ac.jp
* Corresponding author    
Abstract
Background: Although hematopoietic stem cell transplantation (HSCT) can potentially cure some
hematological malignancies, patients who undergo HSCT experience psychological distress.
However, there have been few studies on the short-term influence of HSCT on psychological
distress.
Methods: The subjects were 71 patients with hematological malignancies who underwent HSCT:
33 with acute leukemia, 19 with chronic leukemia, nine with myelodysplastic syndrome, and 10 with
malignant lymphoma. Psychological distress was assessed prior to HSCT and on the seventh day
after HSCT using the Profile of Mood States (POMS).
Results: With regard to Anger-Hostility, the interaction of time (pre- and post-HSCT) and group
(the four groups) was significant in male patients (p = 0.04), but not in female patients. With regard
to the other subscales of POMS, there was no significant main effect or interaction in male or
female patients.
Conclusion: It may be important to provide psychological support to patients throughout the
period of HSCT in consideration of differences in mood changes associated with the underlying
disease and patient sex in order to provide efficient psychiatric intervention for both better
psychiatric and survival outcomes.
Published: 21 November 2008
BioPsychoSocial Medicine 2008, 2:24 doi:10.1186/1751-0759-2-24
Received: 27 August 2008
Accepted: 21 November 2008
This article is available from: http://www.bpsmedicine.com/content/2/1/24
© 2008 Fukuo et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 4
(page number not for citation purposes)
BioPsychoSocial Medicine 2008, 2:24 http://www.bpsmedicine.com/content/2/1/24Findings
Hematopoietic stem cell transplantation (HSCT) is an
alternative to conventional treatment for patients with
hematological malignancies and can potentially cure sev-
eral malignant diseases. However, about one-third to two-
thirds of patients treated with allogeneic HSCT die due to
a relapse of the disease or from procedure-related compli-
cations such as organ damage and graft-versus-host dis-
ease (GVHD) [1,2]. As such, HSCT is associated with life-
threatening physical morbidity. In addition, patients
undergoing HSCT are obligated to stay in a germ-free
ward for several weeks where they suffer from social isola-
tion. They also have to wait at least two or three weeks
until the success of the HSCT procedure becomes evident,
which can influence their psychological state [3].
It has previously been reported that psychological distress
after allogeneic HSCT may vary with the underlying dis-
ease due to differences in chemotherapies prior to
HSCT[4,5]. In addition, although there have been some
studies on the psychosocial impact of HSCT on patients
undergoing allogeneic HSCT, most of them investigated
comparatively long-term influence [6,7] although
Hjermstad et al. [8] reported the course of anxiety and
depression in HSCT patients from two weeks to one year
after HSCT.
Therefore, the aim of this study was to compare the short-
term changes of psychological distress induced by alloge-
neic HSCT before the advent of successful engraftment in
adult Japanese patients with various underlying diseases.
Subjects were patients with hematological malignancies
who underwent HSCT at The University of Tokyo Hospi-
tal. The inclusion criteria were as follows: a) at least 18
years of age; b) a diagnosis of either acute or chronic
leukemia, myelodysplastic syndrome (MDS), or malig-
nant lymphoma; and c) received allogeneic HSCT
between September 1996 and April 2006 at The Univer-
sity of Tokyo Hospital. Patients were asked to complete
the Profile of Mood States (POMS) [9] twice – once before
entering the germ-free ward and a second time on the sev-
enth day after HSCT. After HSCT, the waiting period for
successful engraftment is at least two or three weeks.
Therefore, we chose the 7th day as the post-HSCT assess-
ment point to investigate mood states at a time well
before the success of the engraftment became evident.
POMS consisted of the following six subscales: Tension-
Anxiety, Depression, Anger-Hostility, Vigor, Fatigue, and
Confusion. The mean scores (SD) of Tension-Anxiety,
Depression, Anger-Hostility, Vigor, Fatigue, and Confu-
sion for men in the Japanese general population (n =
3154) are 12.0 (6.3), 9.9 (9.8), 10.8 (8.2), 14.2 (6.1), 9.3
(6.2), 8.6 (4.7), respectively while those for women in the
Japanese general population (n = 2423) are 12.1 (7.1),
10.9 (10.6), 10.9 (8.8), 13.3 (6.2), 10.2 (6.6), 8.7 (4.8),
respectively [9].
Repeated measures analysis of variance (ANOVA) was
used to compare temporal changes of each subscale of
POMS among four groups: Acute leukemia, chronic leuke-
mia, myelodysplastic syndrome (MDS), and malignant
lymphoma). We separately analyzed male and female
patients because Andorykowski et al. [6] reported that the
influence of HSCT on psychological status was different
between men and women. Age was also compared among
the four groups using ANOVA.
All the procedures and materials were approved by the
institutional review board of the University of Tokyo and
informed consent was obtained from all subjects.
Seventy-one out of 200 eligible patients completed POMS
twice. Male patients consisted of 22 with acute leukemia
(of 64 eligible), 11 with chronic leukemia (of 24 eligible),
six with MDS (of 22 eligible), and six malignant lym-
phoma patients (of 14 eligible). Female patients consisted
of 11 with acute leukemia (of 38 eligible), eight with
chronic leukemia (of 18 eligible), three with MDS (of five
eligible) and four lymphoma patients (of 15 eligible).
There was no significant difference in age among the four
male groups (mean ± SD years: acute leukemia, 37.0 ±
11.9; chronic leukemia, 35.6 ± 10.4; MDS, 45.2 ± 10.0;
malignant lymphoma, 39.7 ± 13.8) or in the female group
(mean ± SD years: acute leukemia, 29.6 ± 10.4; chronic
leukemia, 42.8 ± 12.6; MDS, 31.0 ± 7.0; malignant lym-
phoma, 35.5 ± 16.1).
With regard to Anger-Hostility, the time × group interac-
tion was significant in male patients (p = 0.04) although
mean scores were lower than the mean + SD score for
Anger-Hostility for men in the Japanese general popula-
tion, while there was no significant effect for female
patients (Figure 1). As shown in Figure 1, Anger-Hostility
scores in the male MDS and malignant lymphoma groups
worsened, whereas there was no change in the other two
groups. With regard to the other subscales of POMS, there
was no significant main effect or interaction for male or
female patients.
Contrary to the previous study [4], Anger-Hostility scores
in the chronic leukemia group did not worsen compared
to the other groups. The reason for this discrepancy might
be that many chronic leukemia patients in the present
study had undergone intensive chemotherapy before
HSCT due to blastic crisis or acute exacerbation.
In the present study, the Anger-Hostility scores of patients
with MDS, who had not undergone intensive chemother-
apy, worsened after HSCT. Examples of Anger-HostilityPage 2 of 4
(page number not for citation purposes)
BioPsychoSocial Medicine 2008, 2:24 http://www.bpsmedicine.com/content/2/1/24might include unfocused anger such as "Why is this hap-
pening to me?" This result is consistent with a previously
reported study [4] where patients with chronic leukemia
felt more distress than those with acute leukemia because
many of the patients with chronic leukemia had not gone
through intensive chemotherapy. Future studies are
needed to investigate the reason for the temporal pattern
of change in Anger-Hostility scores in patients with malig-
nant lymphoma.
In the present study, the time × group interaction in
Anger-Hostility was significant for male patients but not
for female patients. There have been few studies on the
influence of gender on psychological states after HSCT.
One study by Sasaki et al. [10] reported that being female
was one of the risk factors for developing mental distur-
bances during isolation. The reason for this difference in
results concerning gender effects on psychological states
after HSCT compared to the previous study is not clear
because the time of the assessment was not the same in
the two studies. Therefore, further prospective studies are
needed to investigate the influence of gender on the psy-
chological state after HSCT.
In the present study we observed a significant interaction
of time (pre- and post-HSCT) and group (the four groups)
in Anger-Hostility (p = 0.04) but not in Tension-Anxiety
or in Depression. These results may partly be due to the
time of the second assessment (one week after HSCT) of
psychological distress. Hjermstad et al. [8] reported that
depressive mood peaked two to four weeks after HSCT
and that anxiety gradually decreased four weeks after
HSCT. However, further studies are needed to investigate
prospective changes in anger or hostility because there has
been no study on anger or hostility after HSCT.
There are some limitations in the present study. First, the
sample sizes of some groups were small, especially for
female patients, thus we could not detect differences
among the groups. Second, many potential subjects who
were eligible did not participate. Finally, some factors that
might influence psychosocial variables, such as family
function [11,12], the presence of a spouse [11] and phys-
ical functioning [13,14] were not controlled or investi-
gated.
In conclusion, it may be important to support patients
throughout the period of HSCT with consideration to dif-
ferences in mood changes that are associated with the
underlying disease and patient sex. Because there have
been studies that address mental disorders during HSCT
[10] and the effect on transplant outcomes of early psy-
Temporal changes in POMS Anger-Hostility score before and after HSCTFigure 1
Temporal changes in POMS Anger-Hostility score before and after HSCT. Changes in Anger-Hostility scores 
between pre- and post-hematopoietic stem cell transplantation (HSCT) are displayed by disease group. For male patients, the 
interaction of time and group was significant (p = 0.04) (A). However, for female patients there was no significant main effect 
or interaction (B). Patients with higher Anger-Hostility scores have more distress. T1, time point of pre-HSCT; T2, seventh day 
after HSCT. The mean score (SD) of Anger-Hostility for men in the Japanese general population (n = 3154) is 10.8 (8.2) while 
that of women in the Japanese general population (n = 2423) is 10.9 (8.8) [9].Page 3 of 4
(page number not for citation purposes)
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chological distress [8], further studies on the influence of
factors such as gender, psychosocial factors and chemo-
therapy before HSCT on mood changes during HSCT may
contribute to efficient psychiatric intervention for both
better psychiatric and survival outcome.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
WF designed the study, collected the data, performed sta-
tistical analyses, interpreted the results, and drafted the
manuscript. KY designed the study, collected the data, per-
formed statistical analyses, interpreted the results, and
drafted the manuscript. YT interpreted the results and
drafted the manuscript. NS, HK, MH, and SI collected the
data, interpreted the results, and drafted the manuscript.
YN, KK, and TT helped collect the data, interpret the
results, and draft the manuscript. MK and AA helped inter-
pret the results, and draft the manuscript. All authors read
and approved the final manuscript.
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Comparison of temporal changes in psychological distress after hematopoietic stem cell transplantation among the underlying diseases of Japanese adult patients

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Gardulf A: Factors associated with poor general health after stem-cell transplantation. Support Care Cancer

Henslee-Downey PJ: Physical and psychosocial status of adults one-year after bone marrow transplantation: a prospective study. Bone Marrow Transplant

Kelly MJ: Stages of bone marrow transplantation: a psychiatric perspective. Psychosom Med

Mental disturbances during isolation in bone marrow transplant patients with leukemia. Bone Marrow Transplant

Perceived social support, family environment and psychosocial recovery in bone marrow transplant long-term survivors. Soc Sci Med

Psychiatric and psychosocial aspects of bone marrow transplantation. Psychosomatics

Psychological distress among adult patients being evaluated for bone marrow transplantation. Psychosomatics

Psychosocial morbidity in bone marrow transplant recipients: a prospective study. Bone Marrow Transplant

Recovery after allogeneic marrow transplantation: prospective study of predictors of long-term physical and psychosocial functioning. Bone Marrow Transplant

Reliability and validity of the Japanese version of the Profile of Mood States.

Stock W: Progress in the treatment of adults with acute lymphoblastic leukemia. Curr Opin Hematol

Targeted chronic myeloid leukemia therapy: Seeking a cure.

The course of anxiety and depression during the first year after allogeneic or autologous stem cell transplantation. Bone Marrow Transplant

WH: Global meaning and psychological adjustment among survivors of bone marrow transplant. Psycho-oncology

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Comparison of temporal changes in psychological distress after hematopoietic stem cell transplantation among the underlying diseases of Japanese adult patients

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