Second Report of Clinical Significance of sFas for DLBCL Treated with CHOP and New Analysis of sFas for DLBCL Treated with R-CHOP.

Introduction: We have previously reported serum concentration of sFas predict a clinical outcome of patients with DLBCL. Here, we added the number of patients and confirmed that a high serum sFas level was associated with unfavorable prognosis of patients with DLBCL.

Patients and methods: We used a prospective, consecutive entry design, and the study protocol was approved by the Institution’s Review Board. Between October 1995 and September 2002 previously untreated 132 patients with DLBCL (Group A: patients treated without rituximab) and between December 2002 and March 2007 previously untreated 75 patients with DLBCL (Group B: patients treated with rituximab) confirmed by biopsy participated in this study. We considered eligible for this study all patients with histologically confirmed diagnosis of DLBCL, according to the Working-Formulation and the WHO classification. Serum sFas was determined using ELISA. Patients were assigned to receive eight cycles of CHOP or THP (tetrahydropyranyl-adriamycin) -COP therapy before September 2002. The patients who had been registered after October, 2002 received the R-CHOP or R-THP-COP therapy. A serum sFas level of 3.0ng /ml was used as the cut-off value in this study. All follow-up data were updated on March 1, 2007.

Results: In Group A: 132 patients were enrolled in this category (82 males, 50 females, age; 14 to 92 years, median; 66 years). IPI scoring was available in all patients; accordingly 18.2% patients were classified as low risk, 25.8% as low-intermediate; 32.6% as high-intermediate, and 23.5% as high risk. Overall, the CR rate was 73.5%; PRs were observed in 7.6% and failures in 18.9%. The CR rates for patients with an sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 51.1% and 81.6%, respectively (P<0.0005). The 5-year OS rates for patients with an sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 19.8% and 61.9%, respectively (P<0.0001). In Group B: 75 patients were enrolled in this category (42 males, 33 females, age; 24 to 88 years, median; 69 years). IPI scoring was as follows; 22.6% patients were classified as low risk, 26.6% as low-intermediate; 21.3% as high-intermediate, and 29.3% as high risk. Overall, the CR rate was 72.0%; PRs were observed in 22.7% and failures in 5.3%. The CR rates for patients with a sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 65.6% and 76.7%, respectively (NS). The 2-year OS rates for patients with an sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 54.7% and 92.2, respectively (P<0.01). Multivariate analysis using the proportional hazards model revealed that sFas concentration significantly correlated with overall survival in both group A and B (p<0.05).

Discussion: The IPI is now considered as the most reliable index. After introduction of rituximab to treat for B cell lymphoma, the change of the prognostic factor is expected. In this examination, initially, we could confirm that sFas was an important prognostic factor for DLBCL in the patients who are treated with CHOP regimen as a result of extending the period of surveillance. In addition, we could show that sFas is a useful prognostic factor for DLBCL in the patients who are treated with R-CHOP regimen, too.

Conclusion: Serum sFas is a significant prognostic factor for DLBCL and a useful tool for selecting the appropriate therapeutic strategy in patients with DLBCL.