This study aimed to assess the anxiety and depression in patients undergoing hematopoietic stem cell transplantation (HSCT).
Eighty-seven adult patients with various hematologic diseases, who were scheduled to receive autologous or allogeneic HSCT, were enrolled. The M.D. Anderson Symptom Inventory and the Hospital Anxiety Depression Scale were applied prospectively at hospital admission (D-14), on the day of transplantation (D day), and at 7 (D7) and 14 days (D14) after transplantation.
The severity of both anxiety and depressive symptoms increased over time, with a peak at D7, and then showed a downturn at D14. Physical distresses also started with mild intensity at base line, which were continuously aggravated until D7, and then a partial recovery afterwards. Approximately, 52% of the participants had significantly high anxiety or depression before the start of HSCT. The occurrence of aggravation of pain, nausea, shortness of breath, and lack of appetite was associated with the development of anxiety during isolation period. The patients with significant baseline anxiety had higher scores on fatigue and shortness of breath items at D7 compared to those without.
Our finding suggests the importance of psychiatric approaches, including preventive measures, for the patients undergoing HSCT.
Hematopoietic stem cell transplantation (HSCT) is a highly aggressive medical therapy among cancer treatments. Patients undergoing HSCT experience critical toxic side effects related to a rigorous conditioning regimen and graft-versushost disease (GVHD), with the risk of mortality from the procedure itself [
Previous researches have shown that approximately 20% of patients develop clinically significant psychiatric disorders, such as depressive disorder, anxiety disorder, or adjustment disorder with anxiety or depressed mood during hospitalization for HSCT [
Although numerous studies have reported the quality of life and physical or psychological burden of the survivors of HSCT, prospective data which examine the experience of patients during hospitalization for HSCT remain scarce [
We conducted a prospective longitudinal study to assess psychological and physical symptom burdens experienced by patients during hospitalization for HSCT. In this study, we also aimed to identify the association between aggravation of anxiety and depressive symptoms and that of physical symptom burdens. We also sought to investigate the impact of anxiety and depression before the start of HSCT on the clinical course of psychological and physical distress during hospitalization.
The subjects were 87 patients with hematologic disease who were scheduled to receive autologous or allogeneic HSCT at St. Mary’s Hospital, The Catholic University of Korea in Seoul, Korea. The patients were recruited from the outpatient clinic after they decided to undergo HSCT treatment following a clinician’s recommendation. Inclusion criteria were transplant eligible patients with hematologic diseases, at least 18 years of age, and the ability to understand the research and to give consent to participate in the study. Of the 116 eligible patients, 93 agreed to participate and provided informed consent. Six could not be assessed due to a change in treatment schedule or a withdrawal from participation. Finally, 87 patients participated in the first assessment.
All patient transplants were performed in laminar airflow, high-efficiency particulate air-filtered rooms until engraftment. In cases of allogeneic HSCT, GVHD prophylaxis was attempted with cyclosporine (for sibling donors) or tacrolimus (for unrelated donors) and short-course methotrexate. Granulocyte-colony-stimulating factor was administered subcutaneously to all patients from day 7 after the transplant until neutrophil recovery. Low-dose heparin or lipo-prostaglandin E1 was administered with ursodiol to prevent venoocclusive disease. Antimicrobial prophylaxis consisted of ciprofloxacin and intraconazole started at the beginning of the conditioning treatment. Cytomegalovirus prophylaxis consisted of high-dose IV acyclovir until engraftment for all patients. Every patient received Pneumocystis jirovecci prophylaxis with sulfamethoxazole/trimethoprim after engraftment until discontinuation of the immunosuppressant.
Among the 87 participants, 14 dropped out by day 14 (six at D day, seven at D7, and one at D14). Participants were lost due to compromised medical status (n=6, including one death) or a withdrawal from participation (n=8).
This study was approved by the Institutional Review Board of St. Mary’s Hospital, The Catholic University of Korea. All participants signed an informed consent form after receiving a full explanation of the procedure. All research was undertaken in accordance with the latest version of the Declaration of Helsinki (SCMC070T047).
Demographic and baseline clinical characteristics were assessed at pre-visit interviews before admission for HSCT. The study instruments were applied at hospital admission (D-14, day-10 to day-14 prior to transplantation, depending on the conditioning regimen), and subsequently on a weekly basis from the day of transplantation (D day) until discharge. Assessments were performed within 2 days of the scheduled interview. Similar to previous studies, only the data of D-14, D day, D7, and D14 were used in the analysis due to high dropout rates from discharge [
The M.D. Anderson Symptom Inventory (MDASI) [
Descriptive statistics were calculated for demographic and clinical characteristics of the participants. A mixed model for repeated measurement (MMRM) analysis was used to evaluate changes in HADS and MDASI symptom intensities and to evaluate group differences between those who had significant anxiety or depression prior to HSCT and those not, with diagnoses, HSCT methods, gender, and age as covariates. Pairwise logistic regression models were used to assess the association of MDASI symptom items with the occurrence of new anxiety and depression during HSCT. The individual MDASI symptoms item score at D7 was compared between the patients with and without significant anxiety/depression at D-14 using an analysis of covariance (ANCOVA) with the baseline scores, diagnoses, HSCT methods, gender, and age as covariates. All statistical tests were performed using SAS version 8.0 (SAS, Inc., Cary, NC, USA), with a two-tailed value of 0.05, and the power of the sample to detect an effect size was 80%.
The sociodemographic and disease-related characteristics of the subjects are given in
Patients were divided into two groups, those who had significant anxiety or depression prior to HSCT (anxiety group or depression group) and those who did not (non-anxiety group or non-depression group), and their physical symptom scores on MDASI at D7, which was the most critical time point of distress, were compared (
In the current study, the courses of physical symptom burden of the patients undergoing HSCT showed a gradual increase in symptom intensity from baseline to a peak at 7 days after transplantation. It is consistent with the majority of prospective studies which used similar assessment time points [
In the current study, substantial number of patients already had significant level of anxiety and depression even before the start of transplantation. We found approximately half of the participants had HADS anxiety or depression scores>7 at baseline. This finding is notable given that only 3 participants had the past psychiatric history. Our finding seems rather higher compared to previous prospective findings [
It is interesting to note the difference of time course of emotional distress between patients with baseline anxiety or depression and those without.
Patients with baseline anxiety experienced significantly higher distress in the MADSI items of fatigue and shortness of breath at D-7, the most critical time point for distress from HSCT. No significant difference was observed between patients with baseline depression and those without. Additionally, aggravation of various symptoms, such as pain, nausea, shortness of breath, and lack of appetite were associated with newly emerged anxiety during isolation periods, whereas no MADSI symptom items were associated with newly-emerging depression. Numerous studies in cancer patients found that physical symptom intensity is associated with psychological factors such as anxiety and depression [
The current study had several limitations. Generalization of the results should be restricted because the sample size was small, and the study was performed at a single institution. The medication such as benzodiazepines and hypnotics were prescribed on an as-needed basis for patients, which could have affected the response to the assessments of psychological and physical distress. In the current study, to minimize patient burden during HSCT, only two subjective measures were used to assess distress during HSCT. Therefore, only small amounts of data were provided compared with previous prospective studies. However, considering the great degree of side effects such as fever, nausea, and GVHD, even a small amount of paperwork may have been difficult for the patients. Even in healthy populations, the number of questions in scales negatively influences the accuracy of answers [
Despite these limitations, the current study has significant meanings. It contributes to the prospective data of patients who are most difficult to engage in studies due to the considerable burden of side effects. The current results highlight the importance of the psychological distress in patients with hematologic disease and provide a basis for further studies on the benefits of the psychiatric treatment prior to the start of HSCT. Studies examining the efficacy and safety of psychiatric approaches such as medication and psychotherapy before the start of HSCT and studies to distinguish patients who experience persistent psychological symptoms after HSCT are needed.
The authors have no potential conflicts of interest to disclose.
Conceptualization: Ho-Jun Seo, Tae-Suk Kim, Jeong-Ho Chae. Data curation: Ho-Jun Seo, Young-Gun Baek. Formal analysis: Ho-Jun Seo, Jeong-Ho Chae. Investigation: Ho-Jun Seo, Young-Gun Baek. Methodology: Ho-Jun Seo, Byung-Sik Cho, Jeong-Ho Chae. Project administration: Ho-Jun Seo, Jeong-Ho Chae. Resources: Ho-Jun Seo, Byung-Sik Cho. Supervision: Byung-Sik Cho, Jeong-Ho Chae. Validation: Ho-Jun Seo, Yoo Hyun Um. Visualization: Ho-Jun Seo. Writing—original draft: Ho-Jun Seo. Writing—review & editing: Yoo Hyun Um, Jeong-Ho Chae.
Mean scores and cases (%) of HADS at different stage of the isolation periods*. A: HADS anxiety or depression cases were defined as HADS anxiety or depression scores>7, respectively. B: The main time effect in MMRM analysis. HADS: Hospital Anxiety Depression Scale.
HADS anxiety and depression scores across 4 time points by anxiety and non-anxiety group and by depression and non-depression group. A: HADS anxiety scores of anxiety and non-anxiety group. B: HADS depression scores of depression and non-depression group. *time by group effects in MMRM analysis using diagnoses, HSCT method, gender, and age as covariates. HADS: hospital anxiety depression scale, HSCT: hematopoietic stem cell transplantation.
Sociodemographic and disease-related characteristics of the participants (N=87)
Characteristic | N | % |
---|---|---|
Age, years | ||
Mean (SD): 38.1(14.1) | ||
Range: 18–65 years | ||
Gender | ||
Male | 50 | 57.5 |
Female | 37 | 42.5 |
Marital status | ||
Married | 54 | 62.1 |
Unmarried | 30 | 34.5 |
Divorced or widowed | 3 | 3.4 |
Religion | ||
None | 39 | 44.8 |
Protestant | 17 | 19.5 |
Buddhism | 12 | 13.8 |
Catholic | 18 | 20.7 |
Others | 1 | 1.1 |
Education | ||
Less than high school | 13 | 14.9 |
High school degree | 32 | 36.8 |
Above college | 42 | 48.3 |
Economic status (below 2/3 of median wage) | ||
Previous psychiatric treatment | 21 | 24.1 |
Time since diagnosis, months | 3 | 3.4 |
Median: 6 | ||
IQR: 5–15 | ||
Diagnosis | ||
Acute myelogenous leukemia | 22 | 25.3 |
Acute lymphoblastic leukemia | 26 | 29.9 |
Multiple myeloma | 16 | 18.4 |
Non-Hodgkin’s lymphoma | 2 | 2.3 |
Severe aplastic anemia | 10 | 11.5 |
Myelodysplastic syndromes | 8 | 9.2 |
Chronic myelogenous leukemia | 3 | 3.4 |
Type of HSCT | ||
Autologous | 31 | 35.6 |
Allogeneic | 56 | 64.4 |
Conditioning regimen | ||
Chemotherapy only | 28 | 32.2 |
IQR: interquartile range, HSCT: hematopoietic stem cell transplantation
Mean (SD) scores of 6 physical symptom items of MDASI at different stage of the isolation periods
Items of MDSAI | D-14 | D day | D7 | D14 | p |
---|---|---|---|---|---|
Pain | 2.58 (3.20) | 4.22 (2.85) | 5.95 (3.14) | 4.93 (3.24) | <0.001 |
Fatigue | 3.63 (2.89) | 4.55 (2.88) | 5.39 (2.83) | 4.70 (2.65) | <0.001 |
Nausea | 2.10 (2.89) | 5.21 (2.19) | 5.51 (3.62) | 4.13 (3.34) | <0.001 |
Shortness of breath | 1.54 (2.51) | 2.11 (2.54) | 2.90 (3.04) | 2.06 (2.73) | 0.001 |
Lack of appetite | 3.13 (3.25) | 4.71 (3.20) | 5.07 (3.36) | 4.70 (3.03) | <0.001 |
Disturbed sleep | 3.46 (3.33) | 4.78 (3.19) | 4.87 (3.19) | 4.08 (3.10) | <0.001 |
p<0.01,
the main time effect in MMRM analysis.
MDASI: M.D. Anderson Symptom Inventory
The association between newly developed anxiety or depression and aggravation of physical symptoms during isolation periods
Items of MDSAI | New anxiety |
New depression |
||
---|---|---|---|---|
OR | 95% CI | OR | 95% CI | |
Pain | 3.30 | 1.16–9.41 | - | - |
Fatigue | - | - | - | - |
Nausea | 4.55 | 1.39–14.82 | - | - |
Shortness of breath | 4.90 | 1.79–13.40 | - | - |
Lack of appetite | 5.41 | 1.79–16.34 | - | - |
Disturbed sleep | - | - | - | - |
new anxiety/depression and aggravation of physical symptoms were defined as a case of HADS anxiety/depression scores>7 and scores of each symptom item in MDASI >5, respectively.
MDASI: M.D. Anderson Symptom Inventory, HADS: hospital anxiety depression scale, OR: odds ratio, CI: confidence interval
Comparison of mean scores (SD) of physical symptom burdens at D7 between the patients who had significant anxiety/depression prior to HSCT (anxiety/depression group) and not (no anxiety/no depression group)
Items of MDSAI | Anxiety group | Non-anxiety group | p | Depression group | Non-depression group | p |
---|---|---|---|---|---|---|
Pain | 6.60 (2.70) | 5.60 (3.30) | 0.164 | 6.16 (3.12) | 5.68 (3.18) | 0.452 |
Fatigue | 6.55 (2.25) | 4.81 (2.94) | 0.009 |
5.04 (2.83) | 5.84 (2.81) | 0.241 |
Nausea | 6.28 (3.26) | 5.12 (3.75) | 0.186 | 5.67 (3.48) | 5.29 (3.83) | 0.690 |
Shortness of breath | 3.93 (3.31) | 2.38 (2.78) | 0.020 |
2.53 (2.83) | 3.37 (3.27) | 0.198 |
Lack of appetite | 5.52 (3.31) | 4.84 (3.39) | 0.365 | 4.90 (3.29) | 5.29 (3.49) | 0.589 |
Disturbed sleep | 5.03 (3.64) | 4.79 (2.97) | 0.405 | 4.96 (2.81) | 4.76 (3.66) | 0.411 |
p<0.05,
p<0.01,
ANCOVA was performed with baseline scores, diagnoses, HSCT methods, sex and age as covariates.
HSCT: hematopoietic stem cell transplantation