The EORTC QLQ-HDC29: A supplementary module assessing the quality of life during and after high-dose chemotherapy and stem cell transplantation
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:
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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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Cited by (25)
Systematic Review of Patient-Reported Outcome Measures in Graft-versus-Host Disease
2020, Biology of Blood and Marrow TransplantationCitation Excerpt :The EORTC QLQ-High-Dose Chemotherapy (HDC29) is a supplementary module added to the QLQ-C30, designed for recipients of high-dose chemotherapy and HSCT. It adds 29 items, including 6 multi-item scales (gastrointestinal side effects, anxiety, impact on family, body image, sexuality, and inpatient issues), with 8 single-item questions (skin, fever, urinary frequency, bone pain, medications compliance, finishing tasks, ability to reproduce, and distinguishing life priorities) [94]. The QLQ-HDC29 was used in 1 study by Pallua et al. [61] (n = 45; Austria) reporting the Cronbach's alpha of 5 multi-item scales (mean Cronbach's alpha, .70; range, .52 to .82) and indicating acceptable internal consistency.
Acute GVHD prophylaxis plus ATLG after myeloablative allogeneic haemopoietic peripheral blood stem-cell transplantation from HLA-identical siblings in patients with acute myeloid leukaemia in remission: final results of quality of life and long-term outcome analysis of a phase 3 randomised study
2019, The Lancet HaematologyCitation Excerpt :Full details about the design, conduct, analysis, and results of the original study have been previously published.13 During the 2-year ATGFamilyStudy, QoL was assessed by means of two European Organisation for Research and Treatment of Cancer (EORTC) questionnaires—namely, the QLQ-C30, which has been developed for patients with cancer, including the setting of haemopoietic stem-cell transplantation,14 and the QLQ-HDC29 for those having intensive chemotherapy (version 3.0).15 For the long-term study, all the patients randomly assigned in the original study and who provided written informed consent were considered eligible.
Linguistic and content validation of a German-language PRO-CTCAE-based patient-reported outcomes instrument to evaluate the late effect symptom experience after allogeneic hematopoietic stem cell transplantation
2015, European Journal of Oncology NursingCitation Excerpt :It includes items that capture the full range of symptomatic treatment effects that may be experienced across a variety of disease sites and cancer treatment modalities, however to date PRO-CTCAE has had limited testing in SCT settings. SCT-specific PRO measures include the M. D. Anderson Symptom Inventory Bone Marrow Transplantation (MDASI-BMT) (Cleeland et al., 2000), Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) (Cohen et al., 2012), and European Organisation for Research and Treatment of Cancer High-Dose Chemotherapy module (EORTC-HDC29) (Velikova et al., 2007), however these instruments focus on the acute phase, measure a broad range of Health related Quality of Life (HRQOL) constructs, and address only a subset of the symptoms that can occur in long-term SCT survivors. For instance, none of these instruments captures symptoms such as muscle cramping, blurred vision or skin rash, symptoms that are common in long-term post-transplant survivors.
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for patients with Bone Metastases: The EORTC QLQ-BM22
2009, European Journal of CancerCitation Excerpt :During the Phase 1 interviews with bone metastases patients and HCPs, isolation from friends and family was indicated to be highly relevant by both the groups. To maintain consistency with EORTC phrasing of items, this question was adapted to coincide with an item from the High Dose Chemotherapy Module (HDC29).24 The prevalence ratio of all additional EORTC QLQ-BM22 items exceeded 30% with the exception of items 3, 4, 5 and 8 (which are all pain-related items).