8; 95% confidence interval (CI) 0.6–1.0; P = 0.08] (Table 2). Table 2 Prognostic factors for overall survival   Univariate model Multivariate model Factor HR (95%CI) P value HR (95%CI) P value Age (61 ≤) 2.2 (0.8–6.7) 0.15 – - Sex (male) 2.6 (0.7–9.3) 0.14 – - Stage III, IV 7.6 (1.0–5.8) 0.15 – - Extranodal site (2 ≤) 1.7 (0.6–4.8) 0.35 Alvelestat – - LDH (> upper normal limit) 1.8 (0.5–5.8) 0.34 – - Performance status (2–4) 2.8 (1.0–8.1) 0.05 – - RDI (CPA+DOX) per 0.1 0.7 (0.6–0.9) 0.02* 0.8 (0.6–1.0) 0.08 IPI (high/high intermediate) 4.7 (1.3–17) 0.02* 3.8 (1.0–14) 0.05 Albumin (3.5 mg/dl ≤) 0.7 (0.4–1.2) 0.20 – - Prophylactic G-CSF 1.6 (0.5–4.9) 0.44 – - HR: hazard ratio; CI: confidence interval; RDI: relative dose intensity;

CPA: cyclophosphamide; DOX: doxorubicin; G-CSF: granulocyte colony-stimulating factor Factors Influencing RDI The univariate analyses identified advanced age and higher IPI score as risk factors for reduced RDI. In the multivariate logistic analysis of all these factors, only older age remained as a factor that retained persistent statistical significance [odds ratio (OR) = 0.4; 95% CI 0.2–0.8; P = 0.02]. (Table

3). Table 3 Factors influencing RDI (above the Median): Univariate and Multivariate analysis   Univariate model Multivariate model 1 Multivariate model 2 Factor OR (95%CI) P value OR (95%CI) P value OR (95%CI) P value Age (61 ≤) 0.3(0.2–0.8) 0.0099* 0.4 (0.2–0.8) 0.06 0.4 (0.2–0.8) 0.02* Sex (male) 1.3 (0.6–2.9) 0.54 – - – - Stage III, IV 0.8 (0.4–1.9) 0.68 – - – - Extranodal site (2 ≤) 1.0 (0.4–2.3) 1.00 – - – - LDH (> upper normal limit) 0.5 (0.2–1.2) 0.11 – - 0.6 (0.3–1.4) 0.24 Performance status (2–4) 0.6 (0.2–1.5) www.selleckchem.com/products/AG-014699.html 0.24 – - – - IPI (high/high intermediate) 0.4 (0.2–1.0) 0.04* 0.6 (0.3–1.6) 0.33 – - Alb (3.5

mg/dl >) 0.8 (0.5–1.4) 0.50 – - – - Prophylactic Cyclooxygenase (COX) G-CSF + 1.7 (0.7–3.8) 0.22 – - – - IPI: international prognostic index. G-CSF: granulocyte colony-stimulating factor Discussion In DLBL patients, our data demonstrated that a high RDI of CHOP trended towards a significant association with better survival, even when the CHOP was combined with rituximab. Only advanced age was identified as a risk factor for reduced RDI. There are several previous studies of the relationship between the RDI of chemotherapy and survival in aggressive lymphoma. A high RDI of doxorubicin in CHOP, M-BACOD, or MACOP-B chemotherapy [4], a high RDI of each drug (cyclophosphamide, doxorubicin or vincristine) and a high averaged RDI of these three drugs in CHOP for diffuse large cell lymphoma (DLCL) reportedly had a significant, positive impact on survival [5]. In addition, in ACVB chemotherapy for aggressive lymphoma, the averaged RDI of doxorubicin and cyclophosphamide was strongly associated with survival [6].