The EORTC QLQ-HDC29: A supplementary module assessing the quality of life during and after high-dose chemotherapy and stem cell transplantation

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Abstract

High-dose chemotherapy followed by haematopoietic stem cell transplantation can be associated with high physical and emotional distress levels and reduced quality of life. Systematic prospective measurement of impact of therapy on patient quality of life can aid treatment choices and provide better patient information.

We describe the development of a high-dose chemotherapy questionnaire module to supplement the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30). Phases 1–3 of module development were conducted in United Kingdom, Germany, Austria and Norway, according to EORTC QOL Group guidelines. Forty-eight quality of life (QOL) issues were generated from the literature searches and interviews with health care professionals (n = 24) and patients (n = 92). This produced a 50 item provisional module. Further testing in 169 patients resulted in the QLQ-HDC29 module, containing 29 items, conceptualised into six multi-item scales and eight single items.

The EORTC QLQ-C30, supplemented by QLQ-HDC29 will provide a comprehensive QOL measure for the international clinical trials of high-dose chemotherapy.

Introduction

High-dose chemotherapy (HDC) with haematopoietic stem cell transplantation (HSCT) has been applied increasingly during the past 20 years in a variety of clinical situations. The latest European Group for Blood and Marrow Transplantation (EBMT) activity survey reported that in 2003, there were 21,028 first HSCT (66% autologous and 34% allogeneic) and 4179 additional re- or multiple transplants reported from 597 centres in 42 European countries.1 Main indications were lymphoma (55%; 93% autologous), leukaemia (31%; 78% allogeneic) and solid tumours (9%; 92% autologous).

Allogeneic HSCT has been established as the standard consolidation therapy with curative potential in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) in first or subsequent remission according to patients (cyto)genetic profile and risk of relapse.2, 3 However, the benefit of allogeneic HSCT is considerably offset by complications following transplantation, including graft-versus-host disease and toxicity of HDC and radiotherapy.

HDC with autologous HSCT represents standard care in multiple myeloma,4, 5 relapsed Hodgkin’s disease6 or relapsed aggressive non-Hodgkin’s lymphomas7 in younger patients. HDC is experimental in other types of malignant lymphomas including chronic lymphocytic leukaemia (CLL). HDC may be beneficial in patients with solid tumours,8, 9 but is generally regarded as experimental.

Initially, bone marrow was the primary source of stem cells for HSCT. Prospective randomised studies confirmed the advantage of peripheral blood compared to bone marrow as a stem cell source both in malignant lymphoma and solid tumours.10, 11 Today, peripheral blood is the main source of stem cells for autologous HSCT. In allogeneic HSCT, the change in the stem cell source from bone marrow to peripheral blood began later and proceeded more slowly. In 2003, 65% of all allogeneic HSCT were peripheral blood derived, although a debate on differences in acute and chronic graft-versus-host disease following either source of stem cells is still ongoing.1

HDC is associated with significant immediate, intermediate and long-term toxicity. Many of the toxicities from chemotherapy are dose dependent and HDC requiring stem cell transplantation can impair the subjective quality of life more than lower dose regimens during the treatment period and in the long term. The use of total body irradiation (TBI) as a part of high-dose therapy can have an additional negative impact on patients’ functioning. Over recent years a significant number of studies examined the short and long-term impact of HSCT on functioning and quality of life (QOL). High-dose treatment and HSCT are associated with high physical and emotional distress levels and reduced quality of life.12, 13 In the long term, studies reported overall good functional level in HSCT survivors, in spite of problems with emotional well-being, increased fatigue, sleep problems, and sexual dissatisfaction.14, 15, 16 Compared with healthy controls, physical and social functioning is still worse.17 Some studies show that physical recovery occurs earlier than psychological recovery.18, 19 Up to 65% of patients report fatigue and sleeping disorders and these symptoms may persist for several years following SCT.20, 21, 22, 23 Recently, neuropsychological deficits have been investigated in patients undergoing HSCT.24, 25 Problems with memory or attention can be found in nearly 20% of patients in the first year after HSCT.

Most of this research is done in cross-sectional single centre studies, including survivors after treatment and there are relatively few studies investigating QOL prospectively in clinical trials during treatment and in the long term.26, 27 The United Kingdom MRC AML10 trial indicated, in a large cohort, an adverse impact of bone marrow transplantation on professional and leisure activities, and worse sexual and social relationships.28 More specific assessment and replication of such data are required to clarify any reconsideration of treatment strategies, based on QOL data.

The aim of this study was to develop a treatment-specific quality of life (QOL) questionnaire to supplement a widely used core measure (EORTC–QLQ C30),29 in order to assess treatment-specific side-effects/co-morbidity and additional QOL dimensions (emotional, social and family issues) for patients with malignancies treated with high-dose myeloablative treatment with HSCT, including allogeneic/autologous bone marrow transplantation (Auto-BMT/Allo-BMT) or peripheral stem cell transplantation (PSCT).

The module was targeted to cover time during the treatment (usually in-patient) and up to 6 months post-treatment (usually out-patient). In addition, the module was tested in patients who had completed their transplant between 1 and 10 years earlier to assess its applicability to long-term effects.

Section snippets

Study design

The development of the provisional module was according to guidelines published by the EORTC QOL Group30 (http://www.eortc.be/home/qol/Manuals.htm, 12.06.2001). The module development process has four distinct phases (see Table 1), aimed at ensuring validity and reliability.

Phase IV of the module development process consists of psychometric testing and will be carried out on questionnaire data collected in future clinical trials.

Phase I: generation of QOL issues

Relevant QOL issues/themes for patients treated with HSCT were

Phase 1: generation of issues

Thirty-six articles on QOL and psychosocial issues during and immediately after the transplant were identified. Twenty-six were original studies and 10 were reviews. Ten questionnaires were identified that assess QOL aspects relevant to the period of active treatment with HDC and HSCT and these were reviewed. A list of 120 relevant symptoms/issues/co-morbid conditions was compiled and summarised into the following domains:

  • physical (57 issues subdivided into side-effects and complications –

Discussion

The EORTC QLQ-HDC29 has been developed methodologically to measure physical side-effects and important emotional and family issues in patients with different malignancies, undergoing myeloablative treatment. The content of the questionnaire has been determined by the extensive literature search, by interviews with health care professionals (including doctors, nurses, psychologists) and most importantly by interviews with patients themselves. It includes the experiences of professionals and

Conflict of interest statement

No conflict of interest to be declared.

Acknowledgements

This study was partially supported by an EORTC QOL Group Grant.

Galina Velikova is supported by Cancer Research, UK.

Orhan Sezer is supported by research grants from the Hector Stiftung Weinheim, Germany and Deutsche Krebshilfe, Bonn, Germany.

We thank all patients and professionals participating in the study.

We are grateful to Jane Blazeby, Helena Michelson, Maxine Stead and the Module development committee of EORTC QOL Group for their helpful comments and suggestions.

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