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  • Survival-weighted health profile for long-term survivors of acute myelogenous leukemia

    Chiun Hsu1,2, Jung-Der Wang2,3, Jing-Shiang Hwang4, Hwei-Fang Tien2, Shueh-Mei Chang5, Ann-Lii Cheng1,2, Yao-Chang Chen1,6, & Jih-Luh Tang1,2 1Department of Oncology; 2Department of Internal Medicine, National Taiwan University Hospital (E-mail: [email protected]); 3Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, College of Public Health; 4Institute of Statistical Science, Academia Sinica; 5Department of Nursing; 6Department of Laboratory Medicine, National Taiwan University Hospital, Taiwan

    Accepted in revised form 30 July 2002

    Abstract

    The objective of this study was to use survival-weighted psychometric scores (SWPS) to construct a ‘health profile’ for long-term survivors of acute myelogenous leukemia (AML). The study cohort included all patients who had been diagnosed and treated in our institution from 1985 to 1999 and achieved complete remission after standard chemotherapy (n ¼ 259). One hundred and four patients were interviewed by the European Organization for the Research and Treatment of Cancer (EORTC)-QLQ-C30 questionnaire and the brief form of World Health Organization quality of life questionnaire (WHOQOL-BREF) to estimate the quality of life (QOL) function of the cohort. Forty-one patients underwent bone marrow transplan- tation (BMT) as consolidation or salvage therapy; 63 received chemotherapy alone. SWPS for every functioning domain and symptom item was obtained by direct integration of the mean QOL function with the survival function of the cohort. A Monte Carlo method was used to extrapolate the life-long SWPS beyond the follow-up limit. The mean scores of EORTC-QLQ-C30 and WHOQOL-BREF did not differ significantly between patients who received BMT or those who received chemotherapy only (p > 0.01). In mean SWPS, patients who received BMT had significantly (p < 0.01) better SWPS in all of the functioning domains and symptom items of EORTC-QLQ-C30 and all four domains of WHOQOL-BREF. However, when the life-long extrapolation of SWPS was made, these differences diminished in global health and several symptom items of EORTC-QLQ-C30 as well as in the social and environmental domains of WHOQOL-BREF. Patients’ perspective on QOL may be domain-specific and may evolve over time. SWPS may be useful to evaluate the efficacy of different treatment strategies for AML. Confirmation of the relative merit of BMT vs. chemotherapy alone from prospective studies is needed.

    Key words: Acute myelogenous leukemia, Bone marrow transplantation, Chemotherapy, Quality of life, Survival-weighted psychometric score

    Abbreviations: AML – acute myelogenous leukemia; BMT – bone marrow transplantation; EORTC – the European Organization for Research and Treatment of Cancer; QOL – quality of life; Q-TWiST – quality- adjusted survival time without symptoms of disease and toxicity of treatment; SWPS – survival-weighted psychometric score; WHO – the World Health Organization

    Introduction

    Quality of life (QOL) has been increasingly rec- ognized as an important endpoint in the evalua-

    tion of efficacy of cancer therapy [1, 2]. It is especially informative when alternative treatment options are available and when a trade-off between survival benefit and treatment-related toxicity

    Quality of Life Research 12: 503–517, 2003. � 2003 Kluwer Academic Publishers. Printed in the Netherlands.

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  • needs to be considered. Incorporation of QOL assessment into clinical decision making will thus take into account both the quality and quantity of survival.

    Attempts at quantifying and comparing the change of QOL within clinical trials have been made by estimating the quality-adjusted survival time. The Quality-adjusted Time Without Symp- toms of disease and Toxicity of treatment (Q- TWiST), first proposed by Glasziou et al. [3], has been used in clinical trials for patients with several solid tumors [4, 5] as well as hematological ma- lignancies [6, 7]. According to the Q-TWiST de- sign, the overall survival time is partitioned into several health states based on remission status and treatment-related toxicity. Each health state is as- signed a utility weight, and the Q-TWiST is cal- culated by summing the utility-weighted duration of each health state. A sensitivity analysis is needed to provide a range of outcomes to facilitate decision-making. However, since QOL is a multi- dimensional concept involving the patients’ phy- sical, emotional, and social functioning, a single utility value, as used in Q-TWiST analysis, may not reflect all the QOL dimensions that may be variably affected by the disease and the treat- ment.

    An alternative approach is direct integration of the patient cohort’s survival function with the QOL function, the latter can be estimated by a cross-sectional survey of the surviving patients in the cohort, as proposed by Hwang et al. [8]. Since most QOL questionnaires have a multi-dimen- sional construct, the integration of the psycho- metric scores from different dimensions with the survival function will generate a survival-weighted ‘health profile’ of the patient cohort. Furthermore, the calculation of the survival-weighted psycho- metric scores (SWPS) can be extrapolated beyond the follow-up limit of the patient cohort to pro- duce life-long estimation of QOL changes [9, 10]. Therefore, comparison of projected life-long cu- mulative change of the psychometric scores, i.e., the ‘survival-weighted’ psychometric scores, may be feasible and useful in the evaluation of efficacy of different cancer therapies.

    High-dose chemotherapy plus allogeneic bone marrow transplantation (BMT) has an established role in the treatment of acute myelogenous leuke- mia (AML) [11]. It has curative potential for pa-

    tients with disease relapse. Besides, BMT is often recommended as consolidation treatment after induction chemotherapy for young patients who have a human leukocyte antigen (HLA)-compati- ble sibling donor [12, 13] and is associated with a lower rate of disease relapse and longer disease- free survival [14–16]. However, many studies indicated that BMT patients may suffer from prolonged physical as well as psychosocial prob- lems [17–19]. Therefore, the choice between different treatment strategies will depend on both the potential survival benefit and the pa- tient’s long-term subjective QOL assessment [20, 21].

    We herein report the results of SWPS estimation of long-term survivors of adult AML patients. The main purpose of this study is to explore the fea- sibility of using SWPS as an endpoint to compare the efficacy of BMT and conventional chemo- therapy.

    Patients and methods

    Patients

    Between January 1985 and December 1999, a total of 465 adult primary AML patients were diag- nosed and treated at our institution. Two hundred fifty nine of the 347 patients (74.6%) who had received standard induction chemotherapy achieved complete remission and these patients constituted the study cohort. The cohort consisted of 137 men and 122 women, with a median age at diagnosis of 35.7 years (range: 14.1– 77.7 years). As of December 2000, 134 pa- tients died during follow-up and 18 lost to follow- up.

    The design of the current study is to estimate the QOL function of the study cohort by a cross-sec- tional interview of the surviving patients in that cohort (see below). Contact in person on the pa- tients’ visit to the clinic or by telephone was made for all the 107 surviving patients to explain the purposes and process of this study. Three patients refused further contact. Written informed consent was obtained from the other 104 patients and these patients form the basis of the questionnaire inter- view.

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  • Questionnaire interview

    Two QOL questionnaires were used in this study. One is the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 version 3.0 (QLQ-C30 v 3.0), a questionnaire designed specifically for can- cer patients [22]. The 30 items in EORTC-QLQ- C30 were grouped into several functioning do- mains (global health, physical, emotional, role, cognitive, and social functioning) and symptom items that are related to the underlying cancers or their treatment. The Taiwanese Chinese version of QLQ-C30 v 3.0 was verified by EORTC after standard forward–backward translation process and field test (Dr Wei-Chiu Chie, College of Public Health, National Taiwan University). The EO- RTC-QLQ-C30 questionnaire uses a Likert-type scale, an ordinal one, to grade patients’ judgment on different aspects of QOL. The ‘scalability’ of EORTC-QLQ-C30 has been studied by using a non-parametric Mokken scaling model [23, 24]. The result indicated that the scalability of EORTC scales was quite satisfactory except for those of role functioning and cognitive function- ing.

    The other questionnaire is WHOQOL-BREF, a generic questionnaire developed by the World Health Organization. WHOQOL-BREF is a brief form of the original questionnaire WHOQOL-100 and consists of 26 items that are grouped into physical, psychological, social, and environmental domains [25, 26]. WHOQOL-BREF also uses a Likert-type, 5-point scale to grade the patients’ response to QOL items. To ensure scalar equiva- lence among different language versions of the questionnaire, a descriptor study was designed to specify the ‘anchor points’ for the different types of response scales (capacity, intensity, frequency, evaluation). Between the extreme ‘anchors’ of, say, ‘never-always’ or ‘not at all-completely’, interme- diate descriptors that best correspond to the 25, 50, and 75% points between the two anch

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