Stigma after being newly diagnosed with acute leukemia: the contributing factors among those patients

Objective: To date, little research has been done to answer whether people with acute leukemia (AL) experience stigma. No previous studies investigated stigma and its relationship with most common negative emotion and coping styles in patients newly diagnosed as AL. Therefore, the study was designed to nd out stigma and its possible contributing factors among the patients with initial diagnosis of AL. Methods: A total of 167 patients newly diagnosed as AL were recruited and investigated by Social Impact Scale (SIS), Medical Coping Modes Questionnaire, Hospital Anxiety and Depression Scale. The data was analyzed by multivariate linear regression to identify inuencing factors of stigma. Results: The mean score of SIS was 60.61 ± 9.45, with 13.17% of patients at high level. Almost individuals experienced anxiety or depression during rst chemotherapy after diagnosis. The main coping strategy was acceptance-resignation. Patients with following characteristics tend to experienced stronger stigma: male, childless, lower family income, higher degree of dependence, having chronic diseases, more severe depression, and tendency to adopt acceptance-resignation. Conclusions: Patients newly diagnosed as AL were in moderate level of stigma. Effective measures were suggested to alleviate stigma the patients undergoing when struggling for complete remission, especially for those exposed to risk factors of stigma.

It has long been recognized that various types of illnesses, including hematologic malignancy, are associated with stigma [8,9], which now being considered as a pervasive fundamental cause of population health inequalities [10]. Stigma and its concept were rst mentioned in 1963 by sociologist Goffman [8]. It was described as an attribute which is deeply discrediting due to the blemishes of body image, unpleasant stereotypes individual having, or being a member of an undesirable social group. In 2000, Fife put forward a concept in analysis of the relationship between mechanisms of stigma and the self (self-esteem, body image, and mastery) [11]. In his study, the conceptualization of stigma is grounded in Modi ed Labeling Theory. Based on this basis, he constructed the Social Impact Scale (SIS) containing four dimensions named social rejection, social isolation, nancial insecurity, and internalized shame as a tool to assess the cancer-related stigma. It is generally believed that public stigma is related to social discrimination and patients' negative self-perception, which can be internalized into internal stigma [12] and lead to proximal or distal consequences such as delay in seeking medical treatment [13], decline in treatment adherence [14], poor health outcomes, reduced chance for survival, lower QOL or even abandoning therapy in desperation.
When people diagnosed with AL, they already developed with various functional impairments due to anemia, infection, or hemorrhage trend. The severity of the illness, and the decrease in functional healthy status, did result in patients unable to participate in normal social life and setting them apart from others [5]. Consequently, the more social isolated they involving, the more social rejected they may feel.
Besides, the cost of AL treatment is enormous, some chemotherapy drugs are not covered by the basic medical insurance system in China. This could evidently bring grievous socioeconomic pressures for most patients, especially disadvantaged groups labeled as drain on economy or having urgent demand for social welfare in very beginning [15], putting them in particular risk for low self-esteem [6].
What's more, in China, people seldom talk about deaths for it was ominous. Even after con rmation of AL diagnosis, the desire to maintain normality in life can sometimes make them go to extreme lengths to conceal self-image disorder from others. Some social taboos frequently prevent individuals from seeking conventional health-care help, especially for socially stigmatized diseases such as cancer [16]. For those survivors, they concern about the disclosure of their medical history, making them feel more vulnerable to the "internalized shame", thus leading to the occurrence of stigma. Given the circumstances and characteristics of AL, we thereby use SIS to assess the level of stigma among patients in our study.
Numerous studies [5,17] have demonstrated anxiety and depression are two most common mental health disorders and negatively affect clinical outcomes in patients with AL. Regardless of highly developed medical science and increased survivorship, when people newly diagnosed with incurable disease, they experience with co-morbid depression or anxiety, and it was signi cantly associated with stigma[18]. Those with high level of depression or anxiety are predisposed to developed negative attitudes toward cancer, to hold stereotypical views of themselves and to specially reinforce the feelings of stigma [19,20].
Such circumstance can also be found in AL patients during our clinical daily work. So, we wonder and want to identify if these two very common negative emotions contribute to stigma in patients newly diagnosed as AL.
Coping represents the strategies that individuals use to manage the internal and external demands and plays a crucial role in people instinctively reacting to life stressors, threats, or speci c situation they encounter [21]. After diagnosed as AL, they may experience a variety of practical, social, emotional, and existential concerns due to the disease, side effects of treatments, and poor prognosis [22]. As to AL patients, it's quite clear that positive coping is associated with higher QOL, reduced depressive symptoms and better clinical outcomes [23], while negative coping responses were found to be associated with greater stigma [24,25]. When people adopt positive coping skills, like being active in seeking for solutions or feeling con dent in their coping strategies, stigma decreases [26]. Therefore, we aim to nd out whether coping strategy, the important variable, is related to stigma in AL patients, and can be considered as protective factor as other studies have revealed.
The occurrence of cancer stigmatization among survivors ranges from 13%-80% [20,27,28]. However, little research has been designed to identify whether people with AL experience stigma. Furthermore, no previous studies investigated the prevalence of stigma and its relationship with most common negative emotions and signi cant coping styles in patients newly diagnosed as AL. Based on the hypothesis that stigma experiencing may differ from different cultures and cancer types, therefore, the study was conducted to address the gap in understanding of stigma and its possible in uencing factors among patients with rst diagnosis of AL in China.

Study design and participants
A cross-sectional study was conducted using convenience sampling method in 2 tertiary hospitals of Fujian from August 2017 to May 2019. Hospitalized patients eligible for this study met the inclusion criteria: 1)a diagnosis of AL by clinical bone marrow aspiration for rst time;2 age ≥ 18 years 3 able to read or speak mandarin 4 willing to be enrolled in this study. Participants with mental illness, cognitive disorders, AIDS, other malignances or being not informed of illness after diagnosis were excluded. Before the survey, participates were provided written informed consent and were informed the procedure of the study in detail. Con dentiality was assured in all data for stigma is a sensitive topic. Participates completed the questionnaires by themselves except when they were in doubt or requested standard explanations. All questionnaires lled out were checked and kept in time by researchers.

Demographic & Clinical questionnaire
Demographic information (including gender, age, et al.) and clinical data (eg, type of leukemia, hospital stays) were recorded in Table 1.

Hospital Anxiety and Depression Scale (HADS)
The HADS, designed by Snaith, was introduced into China in 1983 [30]. It has a good rapid screening e cacy and is widely used among cancer patients in hospitals. The scale contains 2 subscales (HAS, HDS), 14 items, adopting 4-point Likert scale (0 = inexistence to 3 = frequently exist). The total scores of each subscale ranges from 0 to 21 (0 to 7, 8 to 10 and 11 to 20 indicates asymptomatic, suspicious and positive respectively). In this study, we choose 10 as the optimal critical value. The Cronbach's coe cient in this study was 0.892.

Medical Coping Modes Questionnaire (MCMQ)
The MCMQ, established by Feifel in 1897 and revised into Chinese version by Shen [31]. It's composed of 20 items covering 3 subscales: confrontation, avoidance, and acceptance-resignation. Each item is rated on 4-point Likert scale (1 to 4), the higher score of the subscale is, the more individual tends to adopt that kind of coping strategy. The Cronbach's coe cient of Chinese version in 3 subscales were 0.69, 0.60, and 0.76 respectively. In this study, the Cronbach's coe cient was 0.721, 0.718, and 0.746.

Statistical methods
The data was stored in Excel and analyzed by SPSS 22.0. The continuous variables and categorical variables were described by range (mean ± standard deviation) and frequencies (percentages) respectively. We compared stigma among patients with different baseline characteristics by using independent samples t tests for 2-level variables or 1-way ANOVA for variables with 3 or more levels.
Pearson's correlation was analyzed to demonstrate the correlations between stigma and anxiety, depression, coping strategies. We put variables from univariate analysis and Pearson's correlation above into multiple linear regressions analysis to determine the statistically signi cant factors that contributing to stigma. An alpha level of 0.05 was selected as criterion for statistical signi cance.

Sample characteristics
A total of 179 patients eligible for inclusion criteria were recruited into our study. 12 of them dropped out because of weakness and fatigue (5 patients

In uencing factors of stigma in patients newly diagnosed with AL
Multiple regression analysis was conducted with stigma score as the dependent variable, while demographic & clinical data, anxiety, depression, and coping strategies as the independent variables. The correlations of these predicting variables were 0.001 ~ 0.588, in a moderate degree of correlation. In the collinearity diagnosis, the tolerance value (TOL) of independent variables was 0.374 ~ 0.876( 0.1), the variance expansion coe cient (VIF) was 1.142-2.765, all of which were below 3, less than 10 of the evaluation index, which means the problem of multiple collinearity among independent variables involved in the regression analysis was not obvious. The results showed that 9 variables were entered into the regression equation after multiple regression analysis. Among them, the greatest contributor was acceptance-resignation, followed by confrontation (Table 3).  [11,24,25] that using SIS to assess stigma of HIV or cancer. As compared to latest studies of them, AL patients scored higher than lung cancer [13] and prostate cancer [14], but lower than HIV [11], colorectal cancer with stoma [12] and breast cancer [14]. The potential underlying reason for the difference may largely due to the type of cancer. The more serious self-image disorder of the disease the patients expose, the more stigma they might trend to experience. Of four dimensions of SIS, Chinese AL patients scores highest in nancial insecurity, followed by internalized stigma. Financial insecurity is a speci c consequence of discrimination related to emerging nancial crisis individual facing [11]. Pricivel et al [32] put forward a conceptual framework of " nancial toxicity" illustrating nancial burden and distress of patients with cancer is nowhere. The latter, in general, are combined with anxiety, depressed and self-blaming. Compared to other types of cancers, nancial insecurity in AL patients seems more pressing, particularly in initial treatment period [32]. Besides, since AL is frequently recognized as one of most panic diseases, patients with AL are thought to be unproductive and too fragile to continue the work [13]. From the observation of our routine work, they do concern a lot about how much treatment was going to cost and whether the family was able to afford? Those who have nancial insecurity were overly concerned about being discriminated and more vulnerable to hold self-accusations of themselves, especially when they have to sale assets or borrow money during induced remission stage. Suggesting clinical care providers should pay attention to the patients who having nancial insecurity.

Medical coping strategies
Coping strategy has a signi cant predictive effect on stigma, and reducing maladaptive coping may largely alleviate experienced stigma [33]. In this study, patients with new diagnosis of AL tend to adopt acceptance-resignation but no confrontation as coping strategy in dealing with their illness and they scored higher than AL patients reported before [34]. Our results indicates that coping strategies are in uencing factors of stigma with acceptance-resignation having strongest impact e ciency. Individuals coping with disease via acceptance-resignation experienced stronger stigma while it's opposite in confrontation. Use of acceptance resignation as a coping strategy was forcefully manifest in lifethreatened patients with little expectation of recovery and appeared to be negatively linked to effectiveness of coping [35,36]. When people diagnosed as AL, the potential unhealthy consequences, uncertain prognosis, and hopeless future do make it di cult for them to take positive coping behavior when confronted with the change of social status, the con ict of family roles, and the distress situation they struggling, which may lead to social discrimination, self-isolation, exacerbating internalized stigma.
Contrary to acceptance-resignation, those taking confrontation showed more positive involvement in treatment compliance, information seeking and emotional self-adjustment without neglecting their physical or psychological health defects [24], suggesting positive coping strategy can be used as protective factor of stigma.

Anxiety and depression
The strong positive correlation between stigma and depression in cancer group was already demonstrated in many studies and depressed individuals were 2 times more likely to experience stigma [20,37]. In our study, 80.84% of AL patients accompany with anxiety while depression occurred in 83.83% of them. Moreover, 70.06% of them experienced two emotions above at the same time. Similar to previous researches, both of them were positively associated with stigma. But only depression was proved to be an in uencing factor of stigma while anxiety was not entered into the linear regression.
which is consistent with a meta-analysis[38], indicating that a higher level of stigma was observed among patients with high depression. Patients with depressive symptoms may be particularly vulnerable to inferiority complex, worthlessness, fear of being ridiculed and isolated, etc. These emotions would further strengthen the stigma, making them repulsive to seek medical treatment or reluctance to interact with others, resulting in condition aggravation and treatment delays.

Demographic and clinical characteristics
In addition to the impact of coping strategies and depression, patients' gender, fertility circumstance, family monthly income, degree of disease dependence and combined with chronic diseases were in uencing factors of stigma, reminding us to pay close attention to how those characteristics as risk predictors contributing to stigma.
Gender in uences feelings of social isolation, social reject, nancial insecurity and internalized shame [11]. Higher stigma experiencing was found in male patients than female, particularly in youth aged 18 ~ 44. That results were consistent with previous qualitative [39], quantitative studies [25,40] or systematic review [13]. Male individuals, under the age of 18 ~ 44 was actively involved in their life. When diagnosed with AL, many of them have to quit jobs and suffer a loss of family role or social status. They were in a large part labeled an undesirable personal trait. Being apart from routine life what it used to be dose yield pessimism and interpersonal relationship predicaments, making them vulnerable to stigma.
The ndings suggested fertility should be consider as an important variable contributing to stigma which had not been reported before. Childless patients in our study undergoing stronger stigma compare to those who already nished fertility. Moreover, they were at high level in internalized shame dimension, with the average of item score (3.1 ± 0.504). However, no association was found between marital status and stigma level in regression analysis which was inconsistent with prior studies [20,27]. In China's traditional conception of fertility, children are life renewing itself and deem to extensions of parents. A healthy body was an inevitably necessary requirement in continuation of the family line. After diagnosed with AL, fertility is basically deprived. Affected by such unacceptable reality and sociocultural stereotypes, patients might unable to complete psychological self-reconstruction.
Family per capita monthly income was demonstrated to be an in uencing factor too, which was consistent with the results of Yilmaz's study [28] but contrary to Meyer's [41]. Depending on Yilmaz's view, low-income level negatively affected cancer-related stigma. The cost of AL treatment is substantial and increasing [32]. Higher income to some extent means lesser pressure to burden expenditure caused by illness. Emerging evidence [10] shows that stigma should be considered alongside the social determinants, such as socioeconomic status, social relationships. The existing economic conditions affect AL patients' attitude towards diseases and self [42], which may subsequently in uence their perception of stigma.
Combined with chronical disease and Increased dependence expose advanced age people to more discrimination [28]. Older patients combined with chronic diseases had been shown to face double stigmatization [10] and display more negative attitudes [20]. Similar ndings were con rmed in our study.
Those two factors are relevant to severity of the illness of the patients, which is also consistent with previous ndings that perceived severity of the illness, or a decrease in functional health status, did result in greater stigmatization [43]. This may due to at least two reasons. Firstly, the more severe illness, the greater dependence, the less able the individuals are to participate in limited activities of daily living. They may generally need caregivers to help them eat, dress even defecate on bed, strengthening their sense of self-shame. Secondly, chronic diseases affected the e cacy and prognosis of the therapy and one of its typical in uence is to prolong the length of hospital stays. Therefore, these two factors may indirectly affect stigma experiencing via deteriorating functional health status.

Study Limitations
The study has several limitations. The objects of this study are mainly concentrated in same area. The stigma and psychological states of AL patients in other provinces remain unknown. Besides, considering stigma is a sensitive topic, although we have ensured con dentiality of all information, a few patients might conceal their true feelings or even reported opposite answer, causing bias in results. Thus, it is suggested to expand sample size to minimize bias so as to con rm these ndings in the future.

Clinical Implications
Stigma is a so common unhealthy psychological state existing in patients with cancer that it is often overlooked. Our study was primarily to identify the level of stigma and its in uencing factors among patients with initial diagnosis of AL in China. Induced remission chemotherapy after diagnosed is deem to an optimal and crucial stage of AL treatment and determines the success or failure of survival. Our ndings emphasized it's equally important for medical staff and caregivers to not merely be focus on induction therapy but also help to relief stigma the patients undergoing when striving for complete remission. Moreover, close attention should be considered for those with following characteristics: male, childless, combine with chronic disease, exposed to nancial crisis or high dependence. For those who exposed to risk factors of stigma, further effective interventions are suggested to alleviate patients' depression as well as to guide them to manage diseases with more positive coping strategies, thus protect them against stigma via these protective factors.

Con ict of Interest statement for all authors
The authors declare no con ict of interest. All authors approved the nal manuscript and have participated su ciently in the work to take the responsibility for appropriate portions of the content.

Availability of data and material
The data that support the ndings of this study are available from the corresponding author upon reasonable request.
Code availability Not applicable.

Author contributions
Rong Hu, and Xiao-Ying Jiang contributed to the study conception and design.Miaoran-Lin, Ying-Chun Lin and Yi-mei Weng were responsible for Material preparation. Data collection and analysis were performed by Miao-Ran Lin. The rst draft of the manuscript was written by Miao-Ran Lin and all authors commented on previous versions of the manuscript. All authors read and approved the nal manuscript.

Ethical approval
The study was performed in accordance with the Declaration of Helsinki and was approved by the Ethics

Consent to participate
Informed consent was obtained from all individual participants included in the study.

Consent for publication
Patients signed informed consent regarding publishing their data.