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Psychosocial Function After Hematopoietic Stem Cell Transplantation

Posted on: Thursday, 3 February 2005, 03:00 CST

The authors report on a prospective cohort study of patients with chronic myelogenous leukemia undergoing allogeneic hematopoietic stem cell transplantation. The purpose was to evaluate the progression of quality of life and mood, as well as patterns of alcohol consumption, a behavior with potential adverse health consequences. Of the 84 subjects who completed serial measures and other interviews at admission for hematopoietic stem cell transplantation and 6-month follow-up, 75 provided data 12 months later. The main findings of this study were that quality of life improves, measures of depressive symptoms decline, and patients drink less alcohol overall. Time was the most important variable accounting for these changes. (Psychosomatics 2005; 46:34-40)

Allogeneic hematopoietic stem cell transplantation (HSCT) is a successful treatment for hematological cancer, acquired marrow failure, genetic hematological diseases, and autoimmune diseases.1 Although associated with significant morbidity and mortality, it is the sole chance of a cure for chronic myelogenous leukemia and certain other diseases.2 The existing literature on survivors of HSCT suggests a relatively high global quality of life after transplantation but also emotional or psychological distress in a significant proportion of patients.3,4

Some general trends have been identified. Mental health outcomes can improve from pretransplant to posttransplant.5,6 Quality of life after transplant, which encompasses physical, psychological, and social phenomena, has been described to improve with time as well.7- 11 Yet, some problems, such as energy level and sleep disturbance, persist, and only a minority of disease-free transplant survivors consider themselves to "have returned to normal" after the treatment.12,13

Little is known about specific behaviors after HSCT, such as alcohol consumption, which may have important health implications.14- 16 A retrospective case-control study of 34 patients17 found that those with lifetime substance abuse or dependence have a significantly diminished probability of survival in relation to comparable patients after HSCT.

Significant methodological problems limit the applicability of many previous findings. Limitations include the use of mixed patient samples (viz., autologous and allogeneic procedures with or without total body irradiation and differing courses of prior treatment for solid and hematological malignancies); retrospective, cross- sectional, or descriptive design; and very small group sizes with high loss to follow-up.3

Thus, a better appreciation of the psychosocial impact of allogeneic HSCT might be gained by focusing on patients with specific diseases. Chronic myelogenous leukemia is the most common indication for allogeneic HSCT and accounts for about 15% of the leukemias.18,19 A prospective study of psychosocial morbidity in 31 bone marrow transplant recipients found that the four patients with chronic myelogenous leukemia had a higher incidence of posttransplant psychosocial morbidity than the patients with other diagnoses. The authors speculated that the lack of previous intensive hematological treatment for chronic myelogenous leukemia accounted for the difference.20 Qualitative and quantitative descriptive data from 28 patients with chronic myelogenous leukemia who received an unrelated donor transplant at least 1 year ago reported an acceptable degree of quality of life in most participants, but that passage of time was unrelated to psychosocial improvement.21'22

The purpose of this prospective study was to evaluate the progression of quality of life, mood, and patterns of alcohol consumption as a measure of a specific behavior with potential adverse health consequences in a cohort of patients with chronic myelogenous leukemia undergoing allogeneic hematopoietic stem cell transplantation. The hypothesis that patients undergoing allogeneic HSCT experience improved psychosocial function in the subsequent 12- month period was tested with serial measures and follow-up interviews.

METHOD

This study reports on 84 subjects, a subset of 114 patients described elsewhere, who survived at least 6 months after HSCT and were therefore able to provide longitudinal data.23 The 114 patients represented 93% of the 122 individuals with chronic myelogenous leukemia admitted for allogeneic HSCT between July 1997 and January 2001. Three individuals declined (3%), and five (4%) were ineligible because they were not English speaking. Seventyfive of the 84 (89%) completed the 12-month study measures. Of the nine subjects without 12-month data, seven died between 6 and 12 months, and two declined further participation.

The subjects' mean age was 44 years (SD = 10). Most were married (70%), men (57%), and Caucasian (93%), with a mean occupational score of 47 (SD = 1 3). The occupation of each participant was scored according to Treiman's Standard International Occupational Prestige Scale 24 as a measure of socioeconomic status in a group for whom income may be adversely affected by illness. Examples of occupations scoring 47 include retail manager and garage operator. The occupational range in the group was 16 (e.g., house cleaner) to 78 (e.g., physician). Forty-seven (56%) smoked cigarettes in their lifetimes, with an average of 10.5 (SD = 20.2) pack-years. Most patients received transplantations within 1 year of a diagnosis of chronic myelogenous leukemia (77%), for disease in the stable phase (89%). The majority (93%) were admitted for myeloablative HSCT, whereas 7% had a T-cell depleted procedure. Most had a six/six human lymphocyte antigen match (86%) from a related sibling or other relative in about half of the cases (52%). The remainder had unrelated donor matches. These demographic and clinical characteristics are summarized in Table 1.

The subjects completed the following measures at the time of admission for HSCT and then 6 and 12 months later: 1) the Functional Living Index-Cancer,25 a validated 22-item measure (original version) to assess the overall functional quality of the patient's day-to-day life with four items referring to today, seven items referring to the past 2 weeks, and one item referring to the past month; 2) the Quality of Life Index,26 a 5-item, physician- administered measure of quality of life over the past week and described to have convergent discriminant and content validity among cancer patients and high internal consistency with Cronbach's alpha = 0.78; 3) the Beck Depression Inventory,27 a 21-item measure for depression with high internal consistency, Cronbach's alpha = 0.92; 4) the Alcohol Use Disorders Inventory,28 a ??-item questionnaire to assess alcohol consumption, symptoms, and consequences of alcohol use in the previous year; and 5) the Alcohol Timeline Followback,29 a drinking assessment method whereby people provide retrospective estimates of their daily drinking in the previous 180 days. These two alcohol measures were chosen because of published reliability studies demonstrating their excellent psychometric properties.30 This study was reviewed and approved by the institutional review board of Brigham and Women's Hospital.

TABLE 1. Demographic and Clinical Characteristics of 84 Subjects Who Received Hematopoietic Stem Cell Transplantation

Data were analyzed with the SAS statistical package (version 8.e, SAS Institute, Gary, N.C.). Simple descriptive statistics were calculated and are reported as means with standard deviations or percentages. A one-sided t test was used to compare changes in measures at 6 months compared to baseline and at 12 months compared to 6 months. In addition, changes over time, from baseline to 12 months, were evaluated for each of our four primary outcome measures (the Functional Living Index-Cancer, the Quality of Life Index, the Beck Depression Inventory, and the Alcohol Use Disorders Inventory), with a repeated-measures analysis of variance (ANOVA). Because the Beck Depression Inventory has seven questions about somatic complaints, separate psychological and somatic scores for the Beck Depression Inventory were calculated for each time point and compared. For the follow-up data at 6 and 12 months, similar repeated-measures regression models were built with the following covariates: time; demographic variables, such as age, sex, and occupation; clinical variables, such as chronic myelogenous leukemia disease stage and interval between chronic myelogenous leukemia diagnosis and HSCT; and psychosocial variables, such as alcohol use. Individual covariates that were univariate significant were entered into a forward selection algorithm in order to determine a final regression model for each outcome measure. Since the univariate predictors were identical to the multivariate predictors, only the multivariate results are presented. A two-sided p value less than 0.05 was considered to be statistically significant.

RESULTS

The means for the longitudinal measures of quality of life, mood, and alcohol use are summarized in Table 2. There were two measures of quality of life: the self-administered Functional Living Index- Cancer and the physician-administered Quality of Life Index. From the patient's point of view, overall functional quality of life improved consistently from the time of HSCT admission (Functional Living Index-Cancer: mean = 102.6, SD = 20.2) to \1 months posttransplant (Functional Living Index-Cancer: mean= 118, SD = 22; t = 5.26, df=72, p<0.0001). There was also improvement between 6 and 12 months (mean= 118, SD = 22, versus mean =125.5, SD = 22.9; t = 3.83, df = 65, p = 0.0003). The range of possible Functional Living Index-Cancer scores is from 7 to 154, and higher scores indicate better functional quality on a day-to-day basis. The overall changes were statistically significant (repeated-measures ANOVA, p<0.0001).

The physician-administered Quality of Life Index, which rates activity, daily living, health, support, and outlook for the past week, with a total score ranging from O to 10, had a different pattern over time. In general, high scores reflect better quality of life, and scores of 3 or less are considered to be very low. At admission for HSCT, the mean score was 8.9 (SD =1.3), and decreased to 8.3 (SD= 1.9) at 6 months posttransplant (t = 2.52, df=82, p = 0.01). The mean score increased to 9 at the 12-month follow-up from the nadir at 6 months (8.3; t = 2.24, df = 69, p = 0.03). The overall changes were statistically significant (repeated-measures ANOVA, p = 0.01 ). The correlation between the Functional Living Index-Cancer and Quality of Life Index scores was r = 0.39 (p = 0.0002) at admission for HSCT, r = 0.67 (p<0.0001) at the 6-month follow-up, and r = 0.73 (p<0.0001) at 12-month follow-up.

The mean Beck Depression Inventory was highest at the time of admission for HSCT (9.6, SD = 6.8), declined somewhat at the 6- month follow-up (9.3), and declined again at the 12-month follow-up (8.0). The changes in Beck Depression Inventory scores over time were statistically significant (repeated-measures ANOVA, p = 0.05). The change from the admission to 6 month mean score was not statistically significant, unlike the difference between the 6 and 12 month Beck Depression Inventory score (t = 2.08, df =68, p = 0.04). All of these mean scores were in the nondepressed range for normal subjects. The percentage of subjects who had scores in the depressed range (≥10) was 32% at admission for HSCT, 36% at the 6-month follow-up, and 26% at the 12-month follow-up.

Separate scores for the psychological and somatic items of the Beck Depression Inventory were calculated and contrasted for the 75 subjects who completed this measure for all three time points and the nine for whom only admission and 6-month data were available. There were no differences between the two groups in either the psychological or somatic scales of the Beck Depression Inventory at admission and 6 months (two-tailed t tests, all p>0.05). Moreover, there were no differences when the scales were compared with repeated-measures ANOVA (F = 2.27, df=1, 80, p = 0.14).

Measures of subjects' alcohol consumption over the course of HSCT showed changes. The subjects drank the most in the 180 days before HSCT (mean =1.6 drinks per drinking day, SD= 1.8, 37% drinking days). Consumption was least in the first 180 days after HSCT (mean = 0.4 drink per drinking day, 5% drinking days) and began to increase between days 181 and 365 after HSCT (mean = 0.8 drink per drinking day, 15% drinking days). These changes were reflected in the serial Alcohol Use Disorders Inventory scores. All changes in the serial indices of alcohol consumption were statistically significant and are summarized in Table 2.

TABLE 2. Longitudinal Psychosocial Measures of 84 Subjects Who Received Hematopoietic Stem Cell Transplantation

In examining the outcome measures at 6 and 12 months, we found through repeated-measures multiple linear regression that time was the only significant predictor of self-reported quality of life, as measured by the Functional Living Index-Cancer (F = 49.29, df=144, p<0.001), although there was a suggestion that men reported a better quality of life than the women (effect estimate = 5.90, SE = 3.52, p<0.10). For physician-rated quality of life, the patients who were younger (effect estimate = -0.03, SE = OOl, p = 0.02) and who had more prestigious jobs (effect estimate = 0.02, SE = 0.01, p = 0.01) had better Quality of Life Index scores. In the adjusted model for Quality of Life Index, time also remained a significant predictor (F = 72.08, df=151, p<0.001). Neither pre-HSCT alcohol use nor Beck Depression Inventory scores were contributory in either measure of quality of life at any time. For the Beck Depression Inventory, significantly higher depression scores were found for women (effect estimate = -3.22, SE= 1.12, p = 0.005), but otherwise, only time was found to be a significant predictor (F = 3.28, df = 149, p = 0.04). Finally, the regression model for the Alcohol Use Disorders Inventory results demonstrated that younger patients (effect estimate = -0.09, SE = 0.03, pO.OOl), men (effect estimate= 1.04, SE = 0.49, p = 0.04), and patients who were lifetime smokers (effect estimate = -1.75, SE = 0.50, p<0.001 ) all had higher scores after treatment. Again, time remained a significant predictor of the Alcohol Use Disorders Inventory score in the adjusted model (F = 32.49, df = 148, p<0.001). No other potential predictors, including clinical measures, were found to be significant in either the univariate or multivariate models.

DISCUSSION

The main findings of this prospective study are that the quality of life in a homogeneous but representative cohort of patients undergoing allogeneic hematopoietic stem cell transplantation significantly improved in the 12-month period after admission for HSCT. Quality of life was measured by patient self-report and a brief physician-administered assessment. Measures of depressive symptoms between 6 and 12 months post-HSCT declined. Because the Beck Depression Inventory includes a number of somatic symptoms, the improvement may reflect physical as well as emotional recovery in the year after HSCT. Univariate and multivariate analyses of potential predictors of quality of life and depressive symptoms consistently demonstrated that time was the most important variable to account for these changes. These findings stand in contrast to other studies of patients with chronic myclogcnous leukemia that showed that time was not related to psychosocial improvement.21'22

There were other important predictors of outcome measures. Subject age (being younger) and occupation (having a more prestigious job) were statistically significant predictors in the multivariate model of the physicianadministered Quality of Life Index, in addition to time. Women had higher Beck Depression Inventory scores, therefore, subject sex was an important predictor, in addition to time, in the multivariate model of the Beck Depression Inventory.

There were some differences between the self-administered Functional Living Index-Cancer and the physician-administered Quality of Life Index. Possible explanations include the differences in the timeframe covered by each measure. While the Functional Living Index-Cancer has been found to be uncontaminated by social desirability issues, it may be that subjects overstated their quality of life when asked by a physician, at least in the hospital. In this study, subjects being younger and having a more prestigious job were predictors of the Quality of Life Index.

The subjects drank the most alcohol before admission for HSCT, least in the 6-month period after HSCT, and more in the last 6 months of follow-up but not as much as pretransplant levels. These changes may reflect adherence to physician recommendations to minimize alcohol consumption after HSCT or physical health status. Age, subject gender, lifetime history of cigarette smoking, and time were statistically significant predictors in the multivariate model for the Alcohol Use Disorders Inventory.

More than half of the subjects (56%) were lifetime cigarette smokers. This is about twice the overall prevalence of cigarette use by American adults.31 While tobacco use is the most prominent cause of respiratory cancers, its role in hematolymphopoietic malignancies is less clear.32"34

Potential limitations to the generalizability of these findings include the relatively small group size of 84 subjects and that the time of follow-up was restricted to 1 year. The group was limited to patients with one type of disease (chronic myelogenous leukemia) undergoing treatment at one center. The subjects were younger than the age typically associated with the onset of chronic myelogenous leukemia. However, this may be explained by the fact that younger patients are more likely to be candidates for HSCT, as reflected in other studies of chronic myelogenous leukemia patients treated in this way.35'36 Information on treatment for depression that some participants may have received was not available, but it is unlikely that the improved Beck Depression Inventory scores could solely be explained in this way. Several items of the Beck Depression Inventory pertain to somatic symptoms, such as appetite and energy; therefore, the improving clinical status of the subject might be reflected in the Beck Depression Inventory score. Although not statistically significant, the Beck Depression Inventory somatic scale score at 6 months was higher for the group that did not complete 12 month measures (of whom seven died) compared to the group that lived (Beck Depression Inventory somatic score: mean = 8.4 [SD = 5.0] versus 4.9 [SD = 2.7]; t = 2.07, df=9, p = 0.07). Indeed, changes in measures that are statistically significant are not necessarily clinically significant. Strengths of the study include its prospective design, consistent use of outcome measures, and minimal loss to follow-up.

Allogeneic HSCT is still the only proven curative approach for patients with chronic myelogenous leukemia and is the mainstay of treatment for younger patients in the chronic phase.37-39 HSCT is the second most frequent major organ transplant in the United States and has the potential for substantial growth and the\rapeutic application to many more diseases. As more people receive and survive HSCT, subsequent quality-of-life issues and other aspects of psychosocial function become increasingly important. Future studies might include patients with chronic myelogenous leukemia treated with allogeneic HSCT at other sites or other methods, such as Gleevec, as well as specific measures of psychological and physical function with longer follow-up.40,41

This study was supported by grants from the Alcoholic Beverage Medical Research Foundation (to Dr. Chang) and the National Institute on Alcohol Abuse and Alcoholism (K24 000289) (to Dr. Chang).

The authors thank research assistants Arti Gehani and Elizabeth Berger and interns Rodney C. Haring and Gregory Michael Brass from the Four Directions Summer Research Program at Harvard Medical School, Boston, who assisted with data collection and entry.

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GRACE CHANG, M.D., M.P.H., E. JOHN ORAV, PH.D.

TAY K. McNAMARA, PH.D., MEI-YEE TONG, M.S.

JOSEPH H. ANTIN, M.D.

Received Oct. 15, 2003; revision received March 24, 2004; accepted April 29, 2004. From the Department of Psychiatry, Brigham and Women's Hospital; the Departments of Psychiatry and Medicine, Harvard Medical School, Boston; and the Dana-Farber Partners Cancer Institute, Boston. Address reprint requests to Dr. Chang, Department of Psychiatry, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115; gchang@partners.org (e-mail).

Copyright 2005 The Academy of Psychosomatic Medicine.

Copyright American Psychiatric Press, Inc. Jan/Feb 2005

Source: Psychosomatics

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