Prognostic Significance of BCL-2 Expression in Patients with Multiple Myeloma

Background: multiple myeloma (MM) remains an incurable disease that accounts for approximately 10% of all hematologic cancers. Patients (pts) with MM treated with conventional chemotherapy have a median overall survival of 36–42 months. Various adverse prognostic factors have been described in MM, including elevated B2 microglobulin, hypoalbuminemia, cytogenetic abnormalities of chromosome 13 (13q14 del, monosomy 13), and elevated CRP among others. BCL-2 mediates anti-apoptotic pathways and its expression has been implicated with lack of response to certain chemotherapeutic agents and unfavorable prognosis in different human malignancies. Objective: to evaluate the prognostic significance of BCL-2 expression in patients with MM. Methods: adult pts who were diagnosed with MM at our institution since 1/1/90 were retrospectively analyzed. Expression of BCL-2 was determined by immunohistochemistry (IHC) staining of deparafinized bone marrow specimens. Median survival was calculated for BCL-2 (+) and BCL-2 (−) groups. Survival curves were estimated according to the Kaplan-Meier method, and were compared with the use of the log-rank test. Median survivals were also compared by using Wilcoxon-Mann-Whitney test. Two-tailed alpha level of 0.05 was considered statistically significant. SAS® software (Cary, NC) was used for statistical analysis. Results: sixty-six patients were initially identified. Forty-four pts were excluded because bone marrow samples were not available for IHC staining. Twenty-two pts (11 males, 11 females), with a median age at the time of diagnosis of 64 years (range: 46 to 83 years) were included for this analysis. Fourteen pts (64%) had positive BCL-2 bone marrow specimens, including 4 mild, 3 moderate, and 7 strong staining, while for 8 pts (36%), bone marrow specimens did not stain for BCL-2. Twelve pts (86%) from BCL-2 (+) group and 4 pts (50%) from BCL-2 (−) group died during the period of follow-up; 8 pts are still alive at the time of this analysis, 23 to 71 months (median: 39 months) after diagnosis. The median survival among BCL-2 (+) pts was 35 months (95% CI: 24 – 69 months) and among BCL-2 (−) pts was 47 months (95% CI: 13 months - N/A). Overall survival did not differ between the two groups (p-values for log-rank and Wilcoxon-Mann-Whitney tests, 0.8256 and 0.7072, respectively). Conclusion: although our study did not show correlation between BCL-2 expression and overall survival, median survival among BCL-2 (−) pts with MM was 34% longer than BCL-2 (+) pts. The authors recognize the limitations associated with this analysis including the retrospective nature of the study, small sample size, and exclusion of a large number of patients. This study highlights the need for prospective evaluation of the prognostic significance of BCL-2 expression among pts with MM.