Qol and Patients' Care

Quality of life and outcomes in patients60 years of age after allogeneic hematopoietic cell transplantation

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Hematopoietic cell transplantation (HCT) has become an established standard of care for many older patients with hematologic malignancies. The effect of transplantation on the quality of life (QOL) of older patients, however, has not been well studied. We thus analyzed QOL in patients 60 undergoing an allogeneic HCT compared with patients <60 years. Prospective psychometric instruments were administered to 351 patients who underwent HCT from 2003 to 2010. Psychometric data were assessed longitudinally by validated questionnaires: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), Coping Inventory and the Profile of Mood State-Short Form. Patients 60 reported better social (P=0.006) and functional well-being (P=0.05) with FACT assessment, and had better total scores, (P=0.043) across all time points. When adjusted for baseline QOL scores as a covariate, social well-being remained significantly better, whereas the other scores became non-significant. With a median follow-up of 49 months, there were no significant differences in OS, relapse-free survival, relapse or chronic GVHD. This study provides further evidence that advanced age should not be a barrier in the decision to pursue allogeneic HCT. Older patients achieved comparable QOL when compared with younger patients.


Allogeneic hematopoietic cell transplantation (HCT) remains the only curative option for many hematologic malignancies. Advances in reduced-intensity conditioning (RIC) and supportive care have now commonly extended the use of HCT to patients 60 years of age.1, 2, 3 Several retrospective studies have compared the outcomes of myeloablative (MA) conditioning and RIC in patients undergoing HCT, and have demonstrated similar survivals.4, 5, 6, 7, 8, 9 Although long-term data on quality of life (QOL) remain limited, recent studies have also suggested similar health-related QOL (HRQOL) and psychosocial functioning (PF) scores following MA conditioning and RIC transplants, and perhaps even an improvement in certain QOL metrics with RIC regimens early in the post-transplant period.10,11 Several studies have also specifically investigated the results of transplantation in older patients and have suggested that older patients undergoing transplant have similar outcomes to their younger counterparts with fewer high-risk features.12, 13, 14, 15, 16 Several analyses investigating non-relapse mortality after HCT have found that older age in itself is not a significant risk factor.1,17, 18, 19 Comorbidities and performance status far outweigh age in predicting how well intensive preparative regimens will be tolerated, and age alone should not be used to exclude patients from undergoing transplantation, even with a MA regimen.20 As allogeneic HCT becomes more of an established standard of care in older patients, measurement of QOL is an increasingly important measurement of morbidity for long-term survivors. We thus undertook a longitudinal study in patients with hematologic malignancies and BM failure syndromes undergoing HCT to compare the HRQOL of patients age 60 with those less than the age of 60.

Patients and methods


The study was approved by the Institutional Review Board at the Cleveland Clinic and informed consent was obtained in accordance with the Declaration of Helsinki. Between June 2003 and December 2010, 435 patients, 18 years of age and older, with a hematologic malignancy or BM failure syndrome scheduled to undergo HCT were approached to participate in QOL assessments. Of the 435 eligible patients, 351 provided the baseline HRQOL assessments prior to transplantation.

QOL instruments

Validated instruments for HRQOL and PF assessment include three self-reported questionnaires: Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT);21 Coping Inventory (Brief COPE)22 and Profile of Moods States Short Form (POMS).23 Questionnaires were given at baseline prior to transplant, and longitudinally, at the time of first post-transplant follow-up and at days 100, 180 and 365. All patients were provided assessments at these time points regardless of events (relapse, GVHD), if alive and willing to participate. The FACT-BMT is a validated 37-item self-report QOL questionnaire, which includes a 10-item BMT subscale. The instrument measures the effect of therapy on domains in physical (PWB), functional (FWB), social (SWB) and emotional well-being (EWB), plus BMT-specific concerns (additional concerns, (AC)), with summary scores, (PWB+FWB+AC) which comprise the trial outcome index; and (PWB+FWB+AC+EWB+ SWB) which comprise the total score. Higher scores in these domains correspond to better HRQOL. Coping strategies were assessed by means of Brief COPE, which is a validated measure of coping strategies rated on a 4-point scale as measured by 14 domains: self-distraction, active coping, denial, substance use, use of emotional support, use of instrumental support, behavioral disengagement, venting, positive reframing, planning, humor, acceptance, religion and self-blame. Lower COPE scores represent worse QOL for denial, substance use, behavioral disengagement and self-blame whereas higher COPE scores represent better QOL on the other 10 domains. The POMS short form has been used to measure mood disturbance or psychological distress associated with cancer treatment. This validated version targets six domains of mood including depression, vigor, anger, tension, confusion and fatigue. Higher POMS scores represent better PF for vigor but worse PF for the other domains.

Study design and statistical methods

This was a longitudinal study comparing collected HRQOL and PF assessments between patients 60 and <60 years of age. Secondary endpoints included OS, relapse, relapse-free survival, and incidence of acute and chronic GVHD.

Categorical variables were compared between 60 and <60 years using the chi-square test, whereas continuous or ordinal categorical variables were compared using the Wilcoxon rank sum test. Serial HRQOL and PF parameters were analyzed with repeated measures analysis of variance. This analysis assesses differences between age groups, differences over time and interaction between age group and time. Significant interaction indicates that differences in age groups are not constant over time, so comparisons between age groups must be made at each time point. If the interaction is not significant, then differences in age groups are reported across all time points with a single P-value. Because of the imbalance of transplant type (MA vs RIC) between age groups, it was included as a variable in the analysis. Repeated measures analysis of variance was done twice; once using baseline data as a time point and again using baseline data as a covariate in the model. If there are differences in age groups in the first analysis but not the second, then age group differences can be explained by the difference in HRQOL at baseline. Because the focus is on comparisons by age, P-values are not shown for the effects of time or transplant type. OS and relapse-free survival were estimated with the Kaplan–Meier method and compared between age groups with the log-rank test. All other outcomes were estimated with the cumulative incidence method and compared using the Gray test. Cox proportional hazards analysis was used to identify univariable prognostic factors for OS. Stepwise Cox analysis with a variable entry criterion of P0.10 and a variable retention criterion of P0.05 was used to identify multivariable prognostic factors. Cox results are summarized as the hazard ratio (HR) and 95% confidence interval (CI) for the HR. All statistical analyses were performed with SAS version 9.2 (SAS Institute, Cary, NC, USA).

Conditioning regimens, GVHD prophylaxis and supportive care

All cases were discussed in a transplant selection meeting and suitability and intensity of conditioning were determined by consensus of physicians, nurses and social workers. RIC was generally offered to patients60 years of age, and those younger than 60 years with significant comorbidities. Intensity of conditioning was defined according to the criteria defined by the Center for International Blood and Marrow Transplant Research (CIBMTR).24 The most common MA regimens included: Bu (i.v. 12.8 mg/kg or orally 14 mg/kg) and Cy (120 mg/kg); Cy (120 mg/kg) and 1200 cGy TBI; and etoposide (60 mg/kg) and TBI 1320 cGy. The most commonly used RIC regimen was Flu (90 mg/m2), TBI 400 cGy. Comorbidities were scored according to the HCT-specific index, and severity was graded as low (score 0), intermediate (score 1–2) and high (score 3) as previously defined.25 GVHD prophylaxis generally consisted of a calcineurin inhibitor, CSA or tacrolimus, in combination with MTX or mycophenolate mofetil. Supportive care was provided according to standard clinical guidelines as previously described.26


Patient, disease and transplant characteristics

Of the 351 patients, 304 were <60 years of age, median 47 years, (range 18–59) and 47 patients were 60 or older, median 62 years, (range 60–70). The majority of patients less than 60, n=256 (84%), underwent a MA transplant, while 48 (16%) received RIC HCT. Most patients60 years of age (37, 79%), underwent an RIC transplant with 10 (21%) patients receiving MA transplant, P<0.001. The most common indication for HCT was AML, with 123 (41%) patients <60 years and 23 (49%) patients 60 years having this diagnosis. Approximately two-thirds of patients in each age group were in remission at the time of HCT, whereas a third had some evidence of active disease. Data on cytogenetic risk were not available on this cohort of patients. Older patients tended to have an intermediate risk HCT comorbidity score (n=24, 51%); the remaining with low-risk (n=12, 26%) or high-risk (n=11, 23%) scores. Comorbidity scores were evenly distributed in patients <60, with 114, (38%) patients with low risk, 87 (29%) intermediate risk and 103 (34%) high risk. Other baseline characteristics are as shown in Table 1.

Table 1 Patient, disease and transplant characteristics

GVHD, relapse and survival outcomes

Incidence of acute GVHD did not differ between age groups. Incidence estimates at day 180 among patients <60 and those 60 were 42 vs 43% grade II–IV, P=0.93; and 16 vs 6% grade III–IV, P=0.14. Incidence of chronic GVHD at 18 months also did not differ (40% for both groups for any chronic GVHD, P=0.72; 24 vs 13% for extensive chronic GVHD, P=0.15). The cumulative incidence of relapse at 5 years was 31 and 43% for patients <60 and 60, respectively, P=0.14. OS at 5 years was 37 and 29% for patients <60 and 60, respectively, P=0.71 (Figure 1). Multivariable analysis of OS for patients <60 revealed that intermediate-risk (HR 1.46, 95% CI 1.01–2.11, P=0.042) or high-risk HCT-CI (HR 1.91, 95% CI 1.35–2.70, P<0.001), active disease at transplant (HR 1.55, 95% CI 1.16–2.08, P=0.003) and HLA mismatch (HR 1.88, 95% CI 1.32–2.68, P<0.001) were associated with greater risk for mortality, while male gender (HR 3.53, 95% CI 1.62–7.71, P=0.002) and an increase in the number of prior chemotherapy regimens (HR 1.27, 95% CI 1.05–1.54, P=0.016 per one regimen increase) were associated with greater risk for mortality in patients 60.

Figure 1

Kaplan-Meier curve of OS in patients <60 and 60 years of age after allogeneic HCT.

Health-related quality of life

Mean HRQOL as measured by the FACT-BMT at baseline and post-HCT for the two groups are shown in Supplementary Table 1. After adjustment for transplant type, patients 60 years had significantly better (higher) scores across all time points post-transplant compared with patients <60 in three FACT domains (social well-being, P=0.006, Figure 2a; functional well-being, P=0.05, Figure 2b; and total summary scores, P=0.043, Figure 2c). There were no differences in regards to physical well-being, emotional well-being or additional BMT concerns. We also did not find any differences in the two groups in regards to areas of mood and psychological distress as measured by the POMS (depression, vigor, anger, tension or confusion) except for worse (higher) scores of fatigue reported by younger patients compared with older patients, P=0.01. We found that older patients had worse (lower) scores on two COPE domains across all time points: use of planning (P=0.012) and humor (P=0.014); however, use of other coping strategies (self-distraction, active coping, denial, substance abuse, emotional support, instrumental support, behavioral disengagement, venting, positive reframing, acceptance, religion or self-blame) were not different among the groups. Adjusting for baseline QOL, however, only social well-being (P=0.002) remained significantly better in older patients compared with younger patients, and no other differences were seen in any of the other domains of FACT, POMS or COPE.

Figure 2

QOL Assessment Scores by Age as measured by the FACT-BMT. (a) Social well-being (b) functional well-being (c) total summary score.

Two COPE domains indicated significant interaction between age group and time: active coping (interaction P=0.018) and behavioral disengagement (interaction P=0.039). Active coping was worse among older patients at day 365 only (P=0.018), and behavioral disengagement was worse among older patients at post-discharge only (P=0.016). These differences became not significant, however, when baseline data was analyzed as a covariate.

QOL assessment attrition

There was significant attrition post HCT over time in our study, and we thus undertook a descriptive analysis to further evaluate the potential effect of GVHD and relapse on completion of QOL assessments. Of the 304 patients <60 years of age, continued participation with QOL surveys within the year of transplant was only achieved by 175 (58%), 166 (55%), 104 (34%) and 85 (28%) patients at first visit post discharge, day 100, 180 and 365, respectively. Similarly, out of the 46 patients 60 years of age, 28 (60%), 19 (40%), 14 (30%) and 12 (26%) had continued participation with QOL assessments by the first visit post discharge, day 100, 180 and 365, respectively. Attrition rate and incidence of acute and chronic GVHD, and relapse are as described for each time point in Supplementary Table 2. By day +365, 219 (72%) patients <60 years had not completed a QOL survey. Of these, 130 patients died, and of the remaining 89 patients, 56 (63%) had acute GVHD, 41 (46%) chronic GVHD and 16 (18%) relapsed disease. Of those who had completed the survey (n=85), 53 (62%) had acute GVHD, 40 (47%) had chronic GVHD and 5 (6%) had relapsed disease. In comparison, 35 (74%) of patients 60 had not completed a QOL survey at day +365. Of these, 18 patients had died, and of the remaining 17 patients, 11 (65%) had acute GVHD, 7 (41%) had chronic GVHD and 4 (24%) had relapsed disease. Of those patients 60 years who had completed the QOL assessment, 7 (58%) had acute GVHD, 6 (50%) had chronic GVHD and none had relapsed. Given the small numbers, we were unable to do a formal analysis on GVHD and QOL within the older age group.


As the field of HCT advances and the number of long-term survivors increases, QOL and patient-reported outcomes are becoming increasingly important. HRQOL is related to the physical, cognitive, emotional, social functioning and well-being of an individual and plays a central role in cancer treatment. It is often cited by cancer survivors as among their greatest concerns.27

Although increasing data suggest that RIC HCT is safe and beneficial in older patients,18,28,29 there remains little data on the impact of HCT on the HRQOL of this population. In addition to finding similar survival outcomes among older and younger patients, our current study also demonstrates comparable HRQOL throughout and after HCT. Older patients reported higher social and functional well-being scores post HCT, translating into higher overall total summary scores and superior QOL at all time points post HCT. However, when adjusted for baseline QOL scores, only better social well-being remained significant. This indicates that reported QOL is different, and generally perceived as better in older patients compared with younger patients prior to transplant, and that this difference persists post HCT. In contrast to previous studies, we did not see any difference in physical well-being in older patients compared with younger patients, (P=0.11),30 perhaps reflecting a fitter older population.

We found a higher incidence of grades III–IV acute GVHD in patients <60 compared with patients 60, 16% vs 6% at day 180; however, this was not significant, and may have been because of the higher proportion of patients <60 receiving MA regimens. Previous studies have found that acute GVHD is highly associated with a decline in QOL after HCT,31,32 and this effect may have contributed to the QOL scores in our younger cohort. A recent paper by Blaise et al.,33 comparing two different reduced intensity conditioning regimens, demonstrated a correlation between the preparative regimen, BU, fludarabine and anithymocyte globulin and decline in HRQOL, primarily attributed to the higher incidences of GVHD and non-relapse mortality with that regimen. Lee et al.31 found that patients who experience grade II–IV acute GVHD and chronic GVHD experience a decline in trial outcome index score at 6 months, whereas at 12 months chronic GVHD alone had the strongest association. Although older age and use of PB cells are risk factors for development of chronic GVHD, we did not find any significant differences in chronic GVHD in our cohort, perhaps because of our limited numbers, and thus are unable to make any conclusions regarding its effect on QOL.

We recognize a number of limitations to our study that must be considered when interpreting these data. This was a single institution study reflecting the participation of a subset of patients undergoing HCT who had completed at least a baseline QOL survey. Inherent in this type of analysis is the selection of fit patients, regardless of age, who were considered eligible for HCT both from a physical and psychosocial perspective. To further assess this, we compared baseline characteristics of the patients who agreed to participate in QOL assessments (n=351) with those who declined participation (n=84). A higher proportion of patients in the group who declined participation were male (64 vs 52%, P=0.045), had a reduced intensity transplant (38 vs 24%, P=0.01) and had a transplant in the latter years (2007–2010), (76 vs 51%, P<0.001), which may have had to do with our institution’s change in social work practices at the time. There were no differences in age, comorbidity index or other survival/GVHD outcomes. Given the comparatively small numbers and differences, it is unlikely that these variances had a large impact on our QOL assessments. We unfortunately did not have complete data on socioeconomic status to compare between all the groups.

In addition, our cohort of older patients was clearly a healthy population highly selected for HCT, as demonstrated by the differences between younger and older patients in prognostic risk factors (HCT-CI, disease status, HLA match) for survival in multivariable analysis. The number of older patients 60 included in this study was much smaller than the population <60 years of age, and represents a highly selected population of patients and an imbalance between the two groups. Because of the limited number of patients 60 completing the QOL assessments, we were not able to discern potential differences in type or degree of acute or chronic GVHD compared with younger patients, which may have affected the QOL. Perhaps most importantly, there was significant post-HCT attrition over time in our study. As previously observed by others, patients with better QOL are more likely to have completed QOL surveys, whereas not returning surveys is significantly associated with subsequent relapse or death.34,35 Although we performed a descriptive analysis of GVHD and relapse events as related to QOL surveys and did not find any major differences in these events in relation to QOL attrition, one would expect that patients experiencing effects of GVHD, disease progression or who die from transplant complications are likely to have worse QOL than survivors of HCT.36 In addition, given the relatively short follow-up, this study does not address important issues of long-term effects of chronic GVHD and transplant leading to late decline of QOL.

Nevertheless, although there have been several studies evaluating HRQOL in RIC HCT compared to MA HCT, this is the first study that specifically evaluates age and HRQOL in HCT. Although it may have previously been assumed that increased age or comorbidities negatively influence HRQOL outcomes in patients undergoing HCT, this study, similar to other studies, demonstrates comparable and even superior outcomes in certain domains of HRQOL in older patients. Perhaps even more interesting and an area worthy of further investigation, is that younger patients specifically reported worse QOL across domains of social well-being, both at baseline and after HCT. It can be hypothesized that older patients may have been more likely to have experienced adversity or health-related problems, making them better able to endure the effects of illness than younger patients. In addition, younger patients may be more affected by non-HRQOL concerns including the adverse effect of HCT on their careers, finances and family/children, including issues of fertility. For example, the ability to return to work or hold a job has often been cited as an important indicator of return to normal life and has previously been used in the assessment of QOL.30 Within a HCT population, one study demonstrated that only 30% of transplant patients were able to return to work at 6 months.30 This may not be an issue for many older patients as they may have retired or not be working and do not have the same social, career or financial stressors that a younger population may have. This current study may help guide further investigation into ways to identify and help a younger population cope and improve post-HCT QOL as the number of young survivors increases.

This study substantiates previous data that when evaluating older patients and weighing the risks and benefits of HCT, age alone should not preclude consideration for transplant. It demonstrates, that in addition to survival, QOL measurements are comparable between older patients who are able to receive a transplant and younger transplant recipients. QOL is actually often perceived as better in older patients compared with younger patients prior to transplant, and this difference persists after HCT. This study should help guide further study on different methods to help improve HRQOL in both younger and older patients undergoing HCT as the number of long-term survivors continues to increase.


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We thank the transplantation team at the Cleveland Clinic Taussig Cancer Institute for their contributions, and all our patients for their participation. We thank Navneet Majhail MD, MS for his constructive review of the manuscript.

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Correspondence to B K Hamilton.

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The authors declare no conflict of interest.

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Hamilton, B., Rybicki, L., Dabney, J. et al. Quality of life and outcomes in patients60 years of age after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 49, 1426–1431 (2014) doi:10.1038/bmt.2014.166

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