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A Systematic Review of Psychosocial Factors Affecting Survival After Bone Marrow Transplantation

Received June 5, 2002; accepted Oct. 24, 2002. From the Department of Psychology, Eastern Michigan University. Address reprint requests to Dr. Hoodin, Department of Psychology, Eastern Michigan University, 537 Mark Jefferson Hall, Ypsilanti, MI 48197; flora.hoodin{at}emich.edu (e-mail).

ABSTRACT

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An electronic database search identified 15 studies of psychosocial factors affecting survival after bone marrow transplantation. The studies were assessed for methodological quality by two reviewers using the procedures of Bland and colleagues. Although some studies found that psychological variables affect survival after bone marrow transplantation, the reviewers' analysis of the methodologically sound studies suggested that survival after bone marrow transplantation is not substantively affected by depressed mood or other psychopathology in adults or by social support in adults or children. Longer survival may be related to lower "anxious preoccupation," higher "fighting spirit," and better quality of life ratings before and soon after transplant in adults. Overall, however, the literature is insufficiently developed to provide definitive evidence for a relationship between psychological variables and survival after bone marrow transplantation. Future primary studies in this area should be designed to maximize replicability and generalizability.

INTRODUCTION

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Although Hippocrates's theories implicated psychosocial variables in the etiology of cancer more than 2,000 years ago,¹ the first scientific studies to systematically and statistically investigate the relationship between patients' psychological qualities and length of cancer survival appeared in the 1950s. Recent reviews have produced no definitive evidence that premorbid psychosocial variables² or psychological intervention³ affect cancer survival rates. Consistent with the theoretical model of Andersen,⁴ the premorbid psychosocial variables that have been most frequently investigated are psychiatric comorbidity (affective distress and coping style) and social support. Similar categories of variables were investigated in the 15 published studies of psychosocial influences on survival after bone marrow transplantation that are discussed in this review.^5–19 Although bone marrow transplantation is a treatment for solid organ and hematological malignancies and other diseases, the transplant protocol is more drastic and life threatening than standard cancer treatments. Consequently, psychological factors and coping repertoires could be hypothesized to have a significantly greater effect on patients' response to bone marrow transplantation procedures and the protracted recovery period thereafter while the immune system reconstitutes. However, to our knowledge, no comprehensive, systematic, critical review of studies examining the relationship between psychosocial variables and survival after bone marrow transplantation has been published.

Such a review is important for clinical as well as theoretical reasons. If psychological variables, in fact, influence the disease process or recovery, identifying high-risk individuals would be imperative. Identification of high-risk individuals could influence clinical management, including decisions about the appropriateness of the procedure for specific patients, allocation of staff time and other resources, and selection of psychological targets for pre- and posttransplant intervention, and could ultimately enhance patients' quality-adjusted life years of survival.

Synthesizing the literature on bone marrow transplantation is not straightforward. The pertinent studies of bone marrow transplantation used a variety of statistical analyses and data collection procedures, and differing, in many cases noncomparable, instruments to assess the psychosocial constructs under investigation. Therefore, to guide this systematic review, we used procedures recommended by Bland and colleagues,²⁰ which include coding the literature, rating the methods and content for quality, and annotating the most methodologically sound studies. The objectives of this systematic review were 1) to identify and summarize objectively all published studies investigating the relationship between psychosocial variables and survival after bone marrow transplantation and 2) to examine the methodological quality of the individual studies and systematically evaluate their findings.

METHOD

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Search Strategy
We searched the MEDLINE and PsycINFO databases for English-language, peer-reviewed studies published as of April 2002 that investigated the effect of psychosocial variables on survival after bone marrow transplantation.

Results of Search
Fifteen primary source studies met the search criteria.^5–19 Three studies focused on pediatric patients.^9,12,16 Of the 12 adult studies,^{5–8,10,11,13–15,17–19} two^10,18 investigated the same group of subjects; hence, in the discussion that follows, we will refer to the two studies jointly when appropriate.

Variables
For the purposes of this systematic review, we treated the medical and demographic variables in the primary source studies as control variables. The medical variables included diagnosis, type of transplant, disease stage, and estimate of risk status. The demographic variables included age, gender, marital status, and education level. As only one study reported quantified information about race or ethnicity,¹³ we did not include ethnicity in our list of demographic control variables.

We grouped the psychosocial independent variables into six categories according to the types of measurement scales used in the studies: social support, depressed mood, other psychopathology, coping style, quality of life, and other. The instruments used in measuring these psychosocial variables are listed in Table 1 by category and are identified by type of assessment, reference for the measure,^21–45 and reference for the study of bone marrow transplantation that used the measure.

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TABLE 1. Measures of Psychosocial Variables Used in 15 Studies of the Relationship Between Psychosocial Variables and Survival After Bone Marrow Transplantation

Methods of Coding and Analysis
To assess the methodological quality of the primary studies and thus the strength of the evidence, we rated each study on six parameters for variations in design and methods. For each parameter, we designated a priori values on a 3-point scale (Appendix 1). The six parameters and the rationale for selecting them were as follows: 1) number of subjects, as studies of insufficient size have a built-in bias toward failing to reject the null hypothesis due to insufficient power; 2) study design, as prospective study design produces the most convincing evidence about causation by reducing confounds such as experimenter effects (e.g., recall bias or ratings affected by knowledge of outcome) and differences due to cohort effects that could operate in cross-sectional studies; 3) statistical soundness, following criteria articulated by Niland and Fisher⁴⁶ for time-to-event and regression models, as the complexity of these statistical procedures often contributes to their misuse and misinterpretation; 4) adjustment for potential medical confounds and 5) for potential demographic confounds, as both medical and demographic confounds could distort the observed relationship between the psychological risk factors and survival, unless the confounds were controlled in the design or analysis stage; and 6) psychometric value of psychosocial measures, as reliability and validity of assessment instruments dictate the potential for replication and generalization.⁴⁷

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APPENDIX 1. Criteria for Rating Study Parameters in a Systematic Review of Studies of the Relationship Between Psychosocial Variables and Survival After Bone Marrow Transplantationa

Reliability of Coded Ratings
The quality of each study was independently assessed by two reviewers, a licensed clinical psychologist and a clinical psychology doctoral candidate. Ratings of 1–3 were assigned to each of the six parameters, and an overall methodological quality score ranging from 6 to 18 was obtained by summing the six individual ratings for each study. Assessment of interrater reliability in the preliminary analyses produced Kendall's taus ranging from 0.58 (p<0.007) to 1.00 (p<0.001) for the individual parameters. The overall ratings of the methodological quality exhibited good reliability (Kendall's tau=0.81, p<0.001). All differences between the two raters were resolved by discussion, and the consensus ratings were used for this review.

RESULTS

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We review the studies of psychosocial variables related to survival after bone marrow transplantation from several perspectives. First, in Table 2, we present an overview of the studies. Next, paralleling our coding system categories, we describe the populations studied, numbers of subjects, type of study design, statistical procedures, and control variables. Thereafter, we discuss the classes of psychosocial variables in greater detail. We conclude by summarizing the most methodologically sound studies.

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TABLE 2. Relationship Between Psychosocial Variables and Survival After Bone Marrow Transplantation in 15 Studies of Adult and Pediatric Subjects

Populations Studied
All of the studies in this review included hematological oncology patients. However, approximately 54% of one group of adult subjects described by both Hoffman et al.¹⁰ and Sullivan et al.¹⁸ consisted of patients with solid organ tumors, and 32% of another group of adult subjects¹⁷ consisted of patients with unspecified diagnoses other than leukemia or lymphoma. In the review that follows, we will address the studies involving adult subjects^{5–8,10,11,13–15,17–19} separately from the pediatric studies.^9,12,16

Sample Size
Sample sizes (specifically, the number of patients whose data were included in the statistical analyses) ranged from 14 to 112 (mean=51; median=52). Seven studies reported sample sizes of less than 50,^{5,7,11–13,15,16} five of 50–100,^8,9,14,17,19 and three of more than 100.^6,10,18 Bearing in mind that, for comprehensive statistical models, the larger the subject-variable ratio, the less likely spurious findings, we awarded higher quality ratings to studies which analyzed more subjects.

Study Design
As a reflection of the difficulties of conducting a systematic review of diverse studies, the distinction between prospective and retrospective designs in the studies we reviewed was not always clear-cut. The majority of the survival studies in this review were prospective^{5,6,9–11,13,15,18,19} and examined the influence of pretransplantation psychosocial variables. Three of the prospective studies^6,9,11 used repeated measures, and one¹³ included a measure of symptom distress assessed 3–4 weeks after transplant as a predictor in the survival analysis. Of the remaining studies, one¹⁴ mixed subjects from a retrospective study with those from a prospective study. Five additional studies were retrospective,^7,8,12,16,17 although one of these¹⁷ was based on retrospective ratings of psychological evaluations conducted before bone marrow transplantation.

Statistical Procedures
Time-to-event analyses, first used in 1988, were reported in eight studies.^{6–8,10,14,15,18,19} Multivariate regression analyses, first used in 1994, were reported in six studies.^{5,6,9,13,18,19} These multivariate studies examined not only the combined influence of interacting medical, demographic, and psychosocial variables but also the unique contribution of each variable while controlling for its intercorrelation with the other predictors. Various other statistical methods were also used in several studies,^8,11,16–18 either in combination with the previously mentioned procedures or in isolation.

Control Variables
Medical variables whose effects were controlled in the statistical analyses included diagnosis,^{5–11,13,15,18,19} type of bone marrow transplantation,^{5–7,9,10,13,15,17,18} disease stage,^8,19 and risk estimate.^5,17 Demographic variables that were controlled included age,^{5–8,11,15,17,19} gender,^{5–8,11,13,17,19} marital status,^5,6,8,13,19 and education.^5,8,17,19 All the studies used at least two demographic variables in describing the characteristics of the subjects. However, in the statistical analyses, one adult¹⁴ and two pediatric^12,16 studies did not control for medical or demographic variables, and three additional adult studies^9,10,18 did not control for demographic variables.

Psychosocial Variables
Psychosocial variables influencing bone marrow transplantation survival were grouped into six categories (Table 2). In our systematic evaluation of the studies, we accorded more weight to methodologically rigorous studies that met our criteria for methodological quality. Methodologically rigorous studies were defined as those with a quality rating at or above the 75th percentile of ratings. We will elaborate further on the detailed ratings in the later section on the overall methodological quality of the studies.

Social support
Of the adult studies, three found evidence for a positive relationship between social support and survival, two^8,17 using investigator-constructed measures and one¹⁵ using a psychometrically substantiated measure. Two studies found no relationship between support and survival; one, using content analysis of semistructured interviews,¹⁹ and the other using a psychodynamically based, investigator-constructed rating scale.¹⁰ Only one study¹⁹ met the methodological quality criteria. The weight of the evidence to date, taking into account the methodological quality of the studies, suggests that more substantive evidence is needed to support a positive relationship between greater social support and increased survival after bone marrow transplantation in adults.

Of the pediatric studies, one¹² found that 1-year survivors and nonsurvivors did not differ significantly in scores on a measure with partial psychometric validation²² but that they did differ in investigator-constructed ratings of family interchange, suggesting that greater social support had a positive effect on survival. Two studies found no relationship between survival and family functioning, one⁹ by using a psychometrically validated measure²¹ and the other¹⁶ by using a clinical rating. In summary, the more methodologically sound study⁹ did not support a relationship between pediatric bone marrow transplantation survival and family functioning as a measure of social support.

Depression
The relationship of depressed mood to survival has been investigated in adult studies only. Five studies^5,6,11,13,14 that used psychometrically validated self-report inventories or structured interviews found no statistical relationship between depressed mood and survival. Four of these five were prospective studies,^5,6,11,13 and one¹⁴ was a mixed prospective and retrospective study. Two studies,^8,17 both employing investigator-constructed ratings retrospectively, found negative relationships between mood and survival: patients with less positive mood died sooner. In summary, the weight of the evidence, based on both the quantity and methodological quality of the findings, is that depressed mood has not been compellingly demonstrated to affect bone marrow transplantation survival in adults.

Psychopathology
In two prospective adult studies using a structured interview¹¹ or psychometrically sound assessment instrument,⁶ no relationship was found between psychopathology and survival. In one retrospective pediatric study,¹² survival was negatively related to child and maternal psychopathology but positively related to paternal psychopathology. In summary, the weight of the evidence, based on both the quantity and methodological quality of the findings, is that psychopathology has no effect on survival after bone marrow transplantation in adults and that any effect of parental psychopathology on survival in children has not yet been convincingly established.

Coping style
Of the six adult studies^{5,6,11,13,14,19} investigating the relationship of coping style to survival, three^5,11,14 employed the Mental Adjustment to Cancer Scale,³⁷ which has four subscales (fighting spirit, helplessness/hopelessness, fatalism, and anxious preoccupation). Of these three studies, two^11,14 with methodological shortcomings found no association between survival and scores on subscales of the Mental Adjustment to Cancer Scale, whereas one⁵ of the more methodologically sound studies found that those with a high level of "anxious preoccupation" died sooner but found no differential effect for "fighting spirit" or other constructs measured by subscales of the Mental Adjustment to Cancer Scale. Apart from methodological differences, a possible reason for the inconsistencies across studies is that the Mental Adjustment to Cancer Scale exhibits instability over time^11,14 and is thus possibly not independent of physical condition, at least when used with bone marrow transplantation patients. Although an additional study¹⁹ found a statistically significant positive relationship between survival and "fighting spirit" before transplantation, this construct was measured by content analysis of semistructured interviews and so may not be the same as the construct assessed by the Mental Adjustment to Cancer Scale. Thus, the weight of the evidence to date, based on methodological quality, is that longer survival after bone marrow transplantation in adults may be associated with a lower level of "anxious preoccupation" (Mental Adjustment to Cancer Scale subscale) and a higher level of "fighting spirit" (not the construct measured by the Mental Adjustment to Cancer Scale subscale). However, these findings require replication.

Other coping style constructs have also been investigated. "Health locus of control," assessed by means of a Dutch rapid assessment instrument,³⁵ was found to be unrelated to survival.⁶ "Distraction," assessed by means of content analysis of semistructured interviews,¹⁹ was inversely related to survival. High self-esteem (as measured by the Dutch 9-item version of the modified Rosenberg Self-Esteem Scale³⁹) was positively associated with survival.⁶ High hopefulness and low acceptance of illness (measured with the modified Jalowiec Coping Scale³⁶) were predictive of longer survival.¹³ Both lower "health care orientation" and higher sexual impairment before bone marrow transplantation (as measured by the Psychosocial Adjustment to Illness Scale³⁸) were predictive of longer survival.¹¹ In pediatric studies, "child motivation for the procedure," assessed by means of subjective, retrospective staff ratings, was unrelated to survival.¹⁶ In summary, no conclusions can be drawn regarding the generalizability of the varied coping style constructs assessed in the studies that were reviewed.

Quality of life
All three adult studies^5,6,13 assessing the quality of life of bone marrow transplantation recipients used psychometrically sound measures; all were prospective and were among the more methodologically rigorous studies. Longer survival after transplant was associated with higher quality of life before transplant⁵ and 3 weeks after transplant (assessed in terms of lower scores on measures of symptom distress).¹³ However, one study,⁶ using a psychometrically validated measure, found that survival after bone marrow transplantation was unrelated to quality of life before transplant, a finding corroborated by an investigator-constructed measure. The single pediatric study that assessed this variable⁹ found no relationship between survival and pretransplant quality of life assessed with a psychometrically sound measure. In summary, the weight of the evidence, based on methodological quality, is that longer survival after bone marrow transplantation may be associated with better quality of life before and soon after transplant in adults but not in children.

Other psychosocial variables
The category of other psychosocial variables comprises disparate variables assessed in four adult studies^7,10,17,18 and one pediatric study.⁹ The findings are reviewed briefly here for the sake of completeness. Longer survival in adults was associated with higher scores on an investigator-constructed, psychodynamically based, composite assessment quantifying family support, "individual maturity," and "ability to communicate a mature psychological construct of transplant."^10,18 Shorter survival time in adults was associated with a history of substance abuse, after the study group was stratified by smoking history.⁷ No statistical relationship with survival in adults was found for clinician ratings of patients' compliance with treatment.¹⁷ In the single pediatric study⁹ in this category, parental marital adjustment was found to have no relationship with child survival. In summary, no conclusions can be drawn regarding the generalizability of the miscellaneous constructs reviewed in this section.

Overall Methodological Quality of Studies
We identified methodologically sound studies as studies that were prospective; that had relatively sound statistical procedures, including a sufficient number of subjects to support the number of variables evaluated; that controlled for medical and demographic variables; and that used psychometrically sound psychosocial measures. The quality ratings for all studies ranged from 7 to 17 (possible range=6–18), with a mean of 12.7 and median of 13. Thus, the overall methodological quality of the studies reviewed here was moderate. The final consensus ratings are displayed in Table 3.

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TABLE 3. Ratings of Methodological Quality of Six Study Parameters for 15 Studies of the Relationship Between Psychosocial Variables and Survival After Bone Marrow Transplantation in Adult and Pediatric Subjectsa

The findings of the most methodologically rigorous studies,^5,6,13,19 which had ratings at or above the 75th percentile on the six study parameters we rated, may be summarized in two ways. One approach is to examine each study for the sequence and number of variables grouped in the particular multivariate model used for the analysis. The value in doing so is that one can examine the unique contribution of any single variable while simultaneously controlling for its covariation with the other variables in that particular model. In different models, the unique contribution of each variable can differ because the contribution of each variable is considered in the light of the contribution of all the other variables in the model.⁴⁸ Further, each model is fitted to a particular sample drawn from a population, and its fit to any other sample, even from the same population, cannot be assumed but must be tested through replication. In this approach, the standardized regression coefficient for each variable provides an estimate of the relative contribution of that variable in terms of predicted change in log (survival) hazard for each unit increase in the predictor in that particular model.

Summarizing the studies with the highest methodological quality in this manner allows for the following observations. In all four studies,^5,6,13,19 the influences of psychosocial variables were investigated after controlling for medical and demographic variables. Longer survival was not found by Broers and colleagues⁶ to be significantly associated with any pretransplant psychological factors (i.e., not depressed mood, psychopathology, health locus of control, functional status, or quality of life), although an association approaching significance was observed for higher self-esteem. Longer survival was found by Andrykowski and colleagues⁵ to be significantly associated with better quality of life before bone marrow transplantation (ß=–0.02) and with lower scores for anxious preoccupation (ß=0.14) but not with depressed mood or fighting spirit. Longer survival was reported by Molassiotis and colleagues¹³ to be associated with higher scores for hopefulness before bone marrow transplantation (ß=2.19), lower scores for acceptance of illness (ß=1.42), and lower symptom distress scores 3 weeks after transplant (ß=0.20) but not with depressed mood before transplant. Longer survival was reported by Tschuschke and colleagues¹⁹ to be associated with higher scores for "fighting spirit" and lower scores for distraction but not with social support (parameter estimates were not reported).

The second approach for summarizing findings is to review the findings by category of psychosocial variable (Table 4). Of the studies of higher methodological quality, one investigated social support,¹⁹ three depression,^5,6,13 and one psychopathology,⁶ but no significant association with bone marrow transplantation survival emerged. All four studies investigated coping style, and three^5,6,13 investigated quality of life. Conflicting findings regarding coping style and quality of life possibly result from psychometric differences among the measures used. Fighting spirit was not associated with longer survival in one study,⁵ which measured that construct by using the Mental Adjustment to Cancer Scale, but was in another¹⁹ that used content analysis to identify the construct. Lower scores for anxious preoccupation⁵ and distraction,¹⁹ higher scores for hopefulness,¹³ and lower scores for acceptance of illness¹³ were associated with longer survival, but health locus of control was not associated with survival.⁶ Longer survival was not associated with quality of life before bone marrow transplantation in one study⁶ but was positively associated in another.⁵ Longer survival was associated with higher quality of life (measured in terms of lower scores for symptom distress) at 3 weeks after transplant.¹³

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TABLE 4. Relationship Between Psychosocial Variables and Survival After Bone Marrow Transplantation in Four Studies With High Ratings of Methodological Qualitya

DISCUSSION

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How strong is the evidence that psychosocial factors affect mortality after bone marrow transplantation? In contrast to a simple narrative review of the literature that would not take methodological quality into consideration, this systematic review suggests that the literature is insufficiently developed to provide adequate and meaningful evaluations of conceivable relationships between the psychosocial variables examined to date and survival after bone marrow transplantation. The weight of the evidence thus far, taking into account the methodological rigor of the research, is as follows. Greater social support has not been substantively shown to be associated with increased length of survival after bone marrow transplantation in adults or children. Neither depressed mood nor other psychopathology has been shown in a methodologically rigorous fashion to have an effect on survival after bone marrow transplantation in adults. Lower scores for "anxious preoccupation" (Mental Adjustment to Cancer Scale subscale), higher scores for "fighting spirit" (not the construct measured by the Mental Adjustment to Cancer Scale subscale), and better quality of life before and soon after transplant may be associated with longer survival in adults, but these findings require replication. In particular, quality of life measures may be confounded with illness severity or stage.

Although several studies have reported a relationship between psychosocial variables and survival after bone marrow transplantation, our analysis of the studies with higher methodological quality suggests that such relationships may be artifacts of methodological shortcomings. Numerous difficulties are inherent in conducting the type of research reviewed here. Studies in this review reported data on patients followed for at least 6 months and data accumulated over a protracted period of time, up to 11 years. Nevertheless, the numbers of subjects in the studies were modest in light of the conditions that must be met for the statistical analyses required to answer the research questions. Thus, biases, confounds, and type II errors are more likely.

A further complication of longitudinal studies is that length of follow-up itself may be a variable that influences the findings. For example, in the first 6 months after transplant, medical risk to allogeneic transplant recipients is greater from transplant-related complications, which could possibly overshadow any influences of psychological variables. However, the relative effect of psychological variables may be greater for autologous transplant recipients in this same time period, since their risk of medical complications is relatively smaller.

Yet another caution derives from the fact that bone marrow transplantation procedures have changed over the years in which the studies were conducted (e.g., the 1980s versus the 1990s). These procedures will continue to change, affecting not only the comparability of earlier and later studies, but also the comparability of data accumulated earlier with data accumulated later within longer-running longitudinal studies. For example, Broers and colleagues⁶ found that even within the 5-year span from 1987 to 1992 in their study, patients who received transplants in a later year had a lower probability of death than those who received transplants a year earlier.

Apart from difficulties already mentioned, the psychosocial measures themselves are a potential source of problems. First, nonlinear relationships between psychosocial variables and prognosis may result in null findings but not trivial relationships. For example, low anxiety and excessive anxiety may both be associated with shorter survival, while a moderate level may be associated with longer survival. Second, comparability among studies is limited due to the use of differing measures of the same variable across studies, as seen for example, regarding fighting spirit and social support. Third, the response formats of the measures may not be appropriate for the sensitivity of the constructs, and therefore the measures may fail to detect significant relationships between the psychosocial variable and survival status. For example, expanding the 4-point Mental Adjustment to Cancer Scale response format to a 7-point Likert response format may increase its sensitivity to differences in fighting spirit, just as a similar expansion of response formats of other scales has been shown to increase their discriminative validity (e.g., reference 49). Last, not all of the instruments used in the studies had established reliability or validity. Some were simply unstandardized ratings devised by the investigators. Ideally, only measures with established reliability and validity should be used in order to minimize random error.

Given such difficulties in designing, executing, collecting, and analyzing data in this domain of research, and given that some investigators have acknowledged the methodological shortcomings of their studies, the reports that have been published are to be commended for blazing a trail. A possible shortcoming of our review is that, in the absence of a standard system for rating study methods, we created a simple system for rating the strength of evidence linking psychosocial variables to mortality after bone marrow transplantation. A different rating system could conceivably result in the selection of a different set of more methodologically rigorous studies.

CONCLUSIONS

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Despite the difficulties we have specified, building a sound body of literature investigating this domain is not only possible but important. Although the overwhelming physical demands of bone marrow transplantation procedures could significantly outweigh any effect of psychosocial variables on survival, the findings from the reviewed studies suggest that this may not necessarily be the case. Identifying high-risk individuals before treatment could enhance decision-making and resource allocation processes and so could contribute significantly to increasing the chances of prolonged survival.

Future research on survival after bone marrow transplantation may benefit by theoretical grounding in Andersen's recently modified influential model of categories of preexisting variables that appear to correlate with psychological difficulties after cancer diagnosis.⁵⁰ These variables include psychiatric comorbidity, medical comorbidity, social support, socioeconomic status, coping style, and health behavior compliance. Research conducted within the framework of this model may hold the key to establishing definitively the psychosocial and other variables that affect recovery and survival in all types of cancer patients. In addition, as indicated by our systematic review, special consideration should be given to methodological rigor. Ideally, studies of survival after bone marrow transplantation should be prospective and statistically thorough, have a large enough number of subjects to support multivariate analyses, control for medical and demographic confounds, and use psychometrically validated psychosocial measures. In summary, future primary studies examining the variables that affect survival after bone marrow transplantation should be designed to maximize replicability and generalizability.

REFERENCES

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