A Predictive Model for Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL): A Retrospective Analysis of 1,252 Cases Performed by the Intergruppo Italiano Linfomi (IIL).

Introduction: few studies have explored the usefulness of a prognostic index specifically devised for patients with localized DLBCL. The IIL has performed a retrospective analysis of a large group of patients with limited stage DLBCL and developed a new prognostic model.

Results: 1,252 patients with localized (Ann Arbor stage I-II) aggressive B-cell lymphoma (IWF: G or H, WHO:DLBCL) diagnosed from 1988 to 2002 and without CNS involvement, treated by 4 cooperative groups and 2 single institutions, are the subject of this analysis. Patient’s median age was 57 years (range, 17–91) and M/F ratio was 1.26. Clinical stage was I in 239 (19%), IE in 303 (24%), II in 356 (28%) and IIE in 354 (28%) patients, respectively. Supradiaphragmatic disease was present in 56% of patients, 13% had > 3 nodal sites, 53% had extranodal involvement, and 7% had >1 extranodal site. Bulky disease (≥10 cm) was present in 26% of patients, ECOG-PS >1 in 12% and B symptoms in 14%. Abnormal biochemical data included: elevated LDH (28%), β_2-microglobulin (B2M;19%) and ESR (38%) and reduced albumin (< 3.5 g/dL) in 21% of the cases. Patients were treated with anthracyclin-containing regimens ± IF-RT. After a median follow-up of 62 months for alive patients (range 1–183 months), 3 and 5-year OS rates were 73% and 71%, respectively. By univariate analysis the following 11 variables were found to be predictive of a short survival: age ≥65 yrs (P=0,0001), stage II nodal (P=0,0001), number of nodal sites (P<0.0001), poor ECOG-PS (P<0.0001), B symptoms (P=0.0009), bulky disease (P=0.0001), elevated ESR (P=0.0001), LDH (P<0.0001), Radiotherapy (P<0.001), B2M (P=0.007) and reduced serum albumin (<0.0001). By Cox multivariate analysis, age ≥65 years (p<0.001), stage II nodal (P<0.001), high LDH (P<0.001) and bulky disease (P<0.01) were indipendent risk factors (RF) for a short survival. The prognostic model was calculated with the sum of scores assigned to each variable; a score of 2 was assigned to advanced age, high LDH, and Bulky; for Stage a score of 1 was considered for stage Ie-IIe and 2 for stage II nodal. Three groups of patients with a different probability of survival (P<0.000001) were identified. Patients at low (Score 0–1; 387 pts), intermediate (Score 2–3; 484 pts) or high risk (Score 4–8; 381 pts) had a 5 years OS of 87%, 77%, 51% respectively. The predictive performance of the model was internally validated through a non parametric Bootstrap method and through residues’ analysis.

Conclusions: This prognostic model, developed and validated on a very large series of patients with localized DLBCL, will allow us to select appropriate therapeutic approaches on the basis of different risk categories.