To evaluate and compare the health-related quality of life (HRQOL) of patients with newly diagnosed CML in the first chronic phase (CML-CP1) receiving HLA-identical sibling donor (ISD) hematopoietic SCT (HSCT) or imatinib, a cross-sectional study that was part of a prospective cohort study at the Institute of Hematology, Peking University was performed. A total of 222 patients including 126 and 96 in the imatinib and ISD HSCT groups, respectively, were enrolled. HRQOL was measured using the Medical Outcomes Study 36-Item Short-Form Health Survey. The ISD HSCT group functioned significantly better on the role-physical functioning and mental health subscales, as well as the mental component summary (MCS) than the imatinib group. HRQOL was generally comparable to groups in the young population. Multivariate analysis showed that white blood cell count⩾30 × 109/L and plts count ⩾450 × 109/L were the major adverse factors affecting HRQOL in long-term survivors. Imatinib therapy was also an adverse factor affecting the MCS (odds ratio=1.7, P=0.032). Thus, long-term CML-CP1 survivors receiving ISD HSCT can attain desirable HRQOL comparable to or better than that of patients receiving imatinib.
With the rapid development of imatinib mesylate and second-generation tyrosine kinase inhibitors (TKIs), the therapeutic algorithm for CML has fundamentally changed. Imatinib is currently well accepted as the first-line treatment for patients with CML in the first chronic phase (CP1). Meanwhile, HLA-identical sibling donor (ISD) hematopoietic SCT (HSCT) is now reserved for patients who have failed to respond optimally to imatinib or second-generation TKIs, or who have relapsed with a T315I BCR-ABL1 mutation.1, 2, 3, 4, 5 Consequently, the annual transplantation rate in CML cases has decreased sharply.6, 7 However, TKI therapy has some limitations; TKIs can only control the disease, and most of the patients in developing countries cannot bear the economic burden of long-term TKI therapy.8 Furthermore, the long-term toxicity of imatinib is unknown. Therefore, ISD HSCT is still an important therapy option for CML-CP1 patients in China.
Both imatinib and ISD HSCT can significantly improve the long-term survival of CML patients.4, 9, 10, 11 Therefore, it is probably inappropriate to evaluate treatment efficacy purely on the basis of survival rate and time. Health-related quality of life (HRQOL) should be considered an important index for evaluating the efficacy of CML therapy. Several studies report the HRQOL of CML patients receiving imatinib or HSCT. Hahn et al.,12 report that imatinib confers better HRQOL than IFN-α plus s.c. low-dose cytarabine as a first-line treatment for CML. Meanwhile, Aziz et al.,13 report that imatinib treatment results in better HRQOL with prolonged treatment, whereas Efficace et al.,14 report that the HRQOL of CML patients is comparable to that of the normal population in many areas. On the other hand, Chang et al.,15 report that HRQOL improves significantly 1 year after HSCT. Moreover, Kiss et al.,16 report that the HRQOL of patients with CML who have survived after HSCT for more than 10 years is generally perceived as good. However, no studies have directly compared the HRQOL between patients with CML treated with imatinib and ISD HSCT.
Therefore, the primary objective of this study was to evaluate and compare the HRQOL of long-term survivors of CML-CP1 treated with imatinib or ISD HSCT and to identify the potential risk factors affecting the HRQOL of these patients.
Materials and methods
This cross-sectional HRQOL study was part of a prospective cohort study at the Institute of Hematology, Peking University (Registration no.: ChiCTR-TNC-10000955). Between April 2001 and March 2010, a total of 348 patients with CML-CP1 were enrolled in this prospective cohort study comparing the medical outcomes of imatinib and ISD HSCT. Upon entering the study, patients were non-randomly assigned to ISD HSCT or imatinib treatment on the basis of whether the patient had an ISD. The detailed inclusion criteria, study protocol and medical outcomes have been published previously.17 Patients who were still alive and at least in CCyR at the end of the study evaluation period in March 2012 were eligible for this HRQOL study, and 222 including 126 and 96 in the imatinib and ISD HSCT groups, respectively, agreed to participate. The response rate was 78.3% in the imatinib group and 66.2% in the ISD HSCT group. Informed consent was obtained from each patient and the study protocol was approved by the ethics committee of Peking University People’s Hospital. The characteristics of the patients are summarized in Table 1.
Assessment of HRQOL
The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) is a widely used HRQOL measure for adults. It includes the following eight subscales: physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. The eight subscales are aggregated to form two summary measures: the physical component summary (PCS) and the mental component summary (MCS), with a population mean of 50 and a s.d. of 10—higher scores indicate better functioning.18, 19
Eligible patients were contacted by phone by the investigators, who informed the survivors of the purpose of the study. A package including a consent form, a set of questionnaires and a self-addressed stamped envelope were mailed to the patients willing to participate. All patients were requested to sign the written informed consent form, complete the questionnaires and return both at their earliest convenience. Patient’s detailed clinical information was gathered through a medical database.
Demographics, disease-related factors and HRQOL were compared between the imatinib and ISD HSCT groups using the χ2 test and Fisher’s exact test for dichotomous variables and t-tests for continuous variables and SF-36 scores.
Univariate and multivariate Cox regression analyses were used to identify the potential factors affecting the HRQOL of CML-CP1 patients. Variables in the univariate analysis included age, sex, Sokal scores, clinical presentations at diagnosis and therapy regimen (that is, imatinib versus ISD HSCT). Clinical presentations at diagnosis included splenomegaly (yes versus no) and laboratory parameters; laboratory parameters at diagnosis included white blood cell count (⩾30 × 109/L versus <30 × 109/L), Hb (⩾120 g/L versus <120 g/L), plts count (⩾450 × 109/L versus <450 × 109/L), peripheral blood blasts (yes versus no), peripheral blood basophils (⩾5% versus <5%) and BM blasts (⩾5% versus <5%). All factors with P<0.1 in univariate Cox regression analysis were included in the multivariate Cox proportional hazard regression model. The level of significance was set at P<0.05. Unless otherwise specified, all reported P-values are two-tailed. All data analyses were conducted with SPSS (SPSS Inc., Chicago, IL, USA).
SF-36 scores of the total population
Patients treated with imatinib functioned significantly better in the bodily pain subscale, whereas patients treated with ISD HSCT functioned significantly better in the role-physical functioning and mental health subscales as well as the MCS. All other domains were comparable between the two groups (Table 2).
SF-36 scores of the young population
We evaluated the HRQOL of patients younger than 30 years of age; we used 30 years as the cutoff, because it was the 25th percentile of the age of the patients in this study. Among the patients younger than 30 years of age, all subscales, and the PCS and MCS scores were comparable between the groups (Table 3).
Risk factors for HRQOL in the total population
In univariate analysis, female sex, white blood cell count, plts count, peripheral blood blasts, peripheral blood basophils, splenomegaly, Sokal scores and imatinib therapy adversely affected the PCS scores. Meanwhile, white blood cell count, plts count, splenomegaly and imatinib therapy adversely affected MCS scores. In the multivariate analysis, white blood cell count ⩾30 × 109/L and plts count ⩾450 × 109/L at diagnosis both significantly adversely affected the PCS and MCS scores. In addition, imatinib therapy significantly adversely affected the MCS scores, whereas female sex significantly adversely influenced the PCS scores (Table 4).
Analysis of non-respondents
The demographics, Sokal scores, clinical presentations at diagnosis and therapy regimens of respondents and non-respondents were compared. There were no significant differences between the groups. In addition, the incidence of chronic graft-versus-host disease was comparable between respondents and non-respondents in the ISD HSCT group (data not shown).
Although there are several studies on the HRQOL of CML patients receiving imatinib or HSCT,12, 13, 14, 15, 16 none compare the HRQOL of long-term CML survivors receiving these two therapies. In the present study, the mean PCS and MCS scores in the imatinib group were 50.7 and 50.7 in the total population and 51.0 and 49.9 in young population, respectively. They are comparable to those of the healthy population, which has a mean of 50 by definition. Furthermore, the HRQOL of the ISD HSCT group was comparable to or better than that of the imatinib group, indicating that CML-CP1 patients receiving ISD HSCT can attain desirable HRQOL.
Some studies report that patients receiving imatinib can attain a desirable recovery of mental health,12, 13, 14 whereas others indicate that the mental health of long-term CML survivors after HSCT is comparable to that of the general population.16 However, which therapy results in a better recovery of mental health remains unknown. In the present study, the MCS scores of long-term survivors in the ISD HSCT group were significantly higher than that in the imatinib group. In addition, imatinib therapy was significantly associated with the lower MCS scores in a multivariate analysis. Worrying about disease progression and the economic burden (imatinib is only reimbursable in a limited no. of cities with high reimbursement barriers in China.20 The annual cost for imatinib in China is U.S. $41 000. Socially disadvantaged patients may be eligible to receive financial help from a government controlled foundation; however, those patients still will be responsible for $10 300 per annum.21) associated with long-term imatinib therapy may adversely affect mental health. Moreover, daily imatinib administration and regular disease monitoring might result in individual psychosocial limitations. On the other hand, several studies demonstrate that HRQOL returns to normal within 3–5 years after HSCT, whereas mental health can recover to desirable levels.22, 23, 24, 25 Some authors suggest that patients faced with the procedure and complications of HSCT pay more attention to and spare more effort toward cultivating their psychosocial domain; a positive attitude is also necessary for a patient to be a long-term survivor.22 Furthermore, an increased feeling of well-being may reflect a sense of personal triumph at overcoming the odds, which could accompany post-transplant survival.26 Thus, patients can report better recovery of mental health after receiving ISD HSCT.
Several studies report that imatinib is effective in children and adolescents with CML-CP1.27, 28 However, imatinib can only control and not ‘cure’ the disease. Furthermore, the long-term (that is, several decades) effects of TKI usage remain unknown. Long-term TKI treatment may also cause potential complications affecting vital organs, such as left ventricular abnormalities.29 Growth retardation is a significant adverse effect of imatinib in prepubertal children.30 Furthermore, Efficace et al.,14 recently reported that young patients receiving imatinib have markedly impaired HRQOL. Therefore, the use of imatinib therapy in young patients remains controversial.31, 32 In the present study, we demonstrated that patients treated with ISD HSCT have HRQOL comparable to that of patients treated with imatinib. HSCT remains the only proven cure for CML, and the outcome of HSCT for CML has improved significantly.4, 33 Furthermore, young patients can attain desirable HRQOL after HSCT. Therefore, ISD HSCT may still be a reasonable therapy option for young patients with CML-CP1.
It is well accepted that splenomegaly and several laboratory parameters including high white blood cell count at CML diagnosis are associated with poor medical outcome.34, 35 In the present study, white blood cell count ⩾30 × 109/L and plts count ⩾450 × 109/L at diagnosis, significantly, adversely affected the HRQOL of long-term survivors; splenomegaly was associated with poorer HRQOL in univariate analysis even though it was not statistically significant and was excluded from the final multivariate analysis. Kiss et al.,16 also report that splenomegaly is one of the most important factors adversely affecting the HRQOL of long-term survivors after HSCT. These results suggest that the parameters that reflect tumor burden might also be relevant to post-therapy HRQOL.
The main limitation of the present study is that a relatively large proportion of patients, particularly the ISD HSCT recipients, did not respond to our invitation to participate. Although our response rate is somewhat low, it is not unreasonable for a cross-sectional study, and it was similar to our previous study.36 It may be related to the lack of a reward for participation or the design of the mailed questionnaire.36 However, certain patients might be unwilling to take part in the study due to poor recovery of HRQOL. To decrease this bias, we found that demographics, Sokal scores, clinical presentations at diagnosis and therapy regimens were all comparable between respondents and non-respondents. Particularly, we observed that the incidence of chronic graft-versus-host disease, which was the most adverse factor affecting HRQOL after HSCT,36 was also comparable between respondents and non-respondents in ISD HSCT group. So non-respondents might have comparable HRQOL to respondents.
In summary, long-term CML-CP1 survivors receiving ISD HSCT can attain desirable HRQOL comparable to or better than that of patients receiving imatinib. Thus, ISD HSCT is an important treatment alternative to imatinib for CML-CP1 patients with available donors.
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We thank the medical editors at Editage, who provided editing assistance to the authors during the preparation of this manuscript.This work was supported by the Key Program of National Natural Science Foundation of China (Grant No. 81230013) and the Beijing Municipal Science & Technology Commission (Z111107067311070).
The authors declare no conflict of interest.
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Cite this article
Mo, X., Jiang, Q., Xu, L. et al. Health-related quality of life of patients with newly diagnosed chronic myeloid leukemia treated with allogeneic hematopoietic SCT versus imatinib. Bone Marrow Transplant 49, 576–580 (2014). https://doi.org/10.1038/bmt.2013.232
- hematopoietic SCT
- health-related quality of life
- identical sibling donor
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