What Have We Learned from Measuring Health-Related Quality of Life in Patients with Chronic Lymphocytic Leukemia? A Systematic Review of Published Studies from 1990 to 2007.

While a large amount of health-related quality of life (HRQOL) studies has been conducted in patients with solid tumors, no data are available for patients with CLL. The aim of the present work was therefore to quantify and evaluate the quality of studies investigating patient’s self-reported HRQOL in CLL patients. A systematic literature search for studies meeting the criteria, published from 1990 to 2007, was undertaken on a number of databases. Candidate articles were mainly searched in PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL). Meeting abstracts at ASCO and ASH conferences were also assessed. We used the following key terms to identify candidate articles “quality of life” and “CLL” or “lymphocytic leukemia” or “chronic leukemia”. All articles included in the review were independently evaluated based on a pre-defined set of methodological issues and criteria by two reviewers (SM and FE). These included a number of methodological and statistical quality criteria such as HRQOL missing data documentation, timing of assessment, rationale for instrument selection and discussion of outcomes in terms of clinical significance. In addition, HRQOL and traditional clinical outcomes were extracted and analyzed. More than 200 candidate articles were evaluated, but only 5 studies met the inclusion criteria for the review. The majority of articles were excluded as HRQOL was not measured by patient’s reported tools. Overall, some 1019 patients were involved in these studies. HRQOL was assessed in 3 prospective randomized controlled trials (RCTs) and 2 longitudinal non-randomized studies. Two of these 5 studies were only published as abstracts. The EORTC QLQ-C30 was the most frequently used measure being utilized in 4 out of 5 studies. Some methodological constraints were identified, mainly in terms of handling of HRQOL missing data and possible lack of sensitivity of the measure being used. The most robust evidence stemmed from a prospective RCT comparing Fludarabine (F) vs. Fludarabine + Cyclophopsphamide (FC) where HRQOL was assessed as a secondary endpoint. While there was no significant HRQOL difference between treatment arms over time, this study showed nonetheless that the newer FC combination had no detrimental effect on patient’s HRQOL compared with the standard F arm. This information definitely reinforces concomitant clinical findings which favor the more intensive FC treatment (e.g. in terms of clinical response and progression-free survival). Taken together, very limited conclusions can to date be drawn with regard to HRQOL issues in patients with CLL in view of the paucity of data in this area. There is urgent need of implementing HRQOL research in patients with CLL and of providing the scientific community with robust evidence-based data on the impact of new treatment approaches in these patients.