Publications

Despite improved responses, chronic lymphocytic leukaemia (CLL) remains incurable with conventional chemotherapy. Patients with poor-risk factors or who fail conventional chemoimmunotherapy are offered autografts, preferably after achieving remission. This report presents the totality of evidence through a systematic review that assessed the efficacy of autografts in CLL. A search of MEDLINE databases from 1966-2006 and hand-search of references identified 82 prospective-randomized, non-randomized comparisons or single-arm trials, of which only nine met our inclusion criteria: two trials were funded by public/government, one by private foundations, one jointly by private/public, and was unclear in five. No randomized controlled trials comparing autografts versus conventional chemotherapy (or chemoimmunotherapy) were found. Six studies were single-arm and three were non-randomized with a control-arm (autologous versus allogeneic). Overall, 361 patients were enrolled, but only 292 were transplanted. Transplant-related mortality ranged from 0% to 9%. Complete responses ranged from 74% to 100% and molecular responses ranged from 57% to 88%. Overall survival ranged from 68% at 3 years to 58% at 6 years. It is uncertain whether autograft is superior to conventional therapy. The high incidence of myelodysplastic syndrome (9-12%) is particularly concerning in CLL, where median survival is 9 years.

PURPOSE: Elderly patients share the majority of the disease burden in cancer. Although 61% of new cancer cases occur among elderly, they comprise only 25% of the patients enrolled onto randomized clinical trials (RCTs). A systematic review to assess the accurate participation of elderly patients in RCTs has not been performed.

PATIENTS AND METHODS: We reviewed all consecutively completed phase III RCTs conducted by five National Cancer Institute-sponsored cooperative groups. Published papers and study protocols were used for data extraction. We used a cutoff age of 65 years to define elderly patients. For trials that did not exclusively enroll elderly, data were extracted on number of participants 65 years of age. Outcome between the innovative and the standard treatment was compared.

RESULTS: Of 345 studies, only one trial exclusively enrolled elderly patients (0.28%); 57% of the trials (n = 197) had no stratification by age, and 12% of the studies had a stratification age 65 years (n = 42). Overall survival in the trial exclusively enrolling elderly favored the newer treatments (hazard ratio [HR], 0.69; 95% CI, 0.47 to 1.02; P = .06). Additionally, in trials enrolling more than 40% of elderly, survival and event-free survival favored the innovative treatments (HR for survival, 0.91; 95% CI, 0.84 to 0.99; P = .03; HR for event-free survival, 0.85; 95% CI, 0.72 to 1.01; P = .07). Treatment-related mortality was similar in both the innovative and standard treatment groups (HR, 0.91; 95% CI, 0.47 to 1.78; P = .8).

CONCLUSION: Our data indicate that enrollment of elderly in experimental RCTs is not associated with increased harm to this patient population. Increased participation of elderly may help in finding new treatments that are clinically applicable specifically to this cohort of patients.

BACKGROUND: The randomized, controlled trial (RCT) is the "gold standard" for establishing the effect of any intervention. This approach, however, is often not feasible with rare diseases such as cutaneous T-cell lymphoma.

METHODS: We review the principles of evidence-based medicine to see which are particularly pertinent to the study of rare diseases.

RESULTS: When an RCT is not feasible, attention is given to determining all the available prior data. Evaluation of the new data and the historic base requires attention to biases, but can allow estimation of a "true" study result.

CONCLUSIONS: Even when an RCT cannot be performed because of insufficient cases, utilization of evidence-based methodology can help minimize bias and maximize the truth of observed new data.

Scientists around the world publish a tremendous amount of biomedical research every year, and the process of synthesizing the published research is an uphill task. Systematic review is the most promising technique to critically appraise and synthesize the findings and also argues for the totality of evidence, which is important for effective oncology management.