Role of the molecular staging and response in the management of follicular lymphoma patients.

Bcl-2/IgH rearrangement is the molecular hallmark of follicular lymphoma which is present in 70 - 90% of cases at diagnosis. The significance of the bcl-2 rearrangement at onset of disease and of its clearing after treatment (molecular response) is still controversial. The aims of the present analysis are: to evaluate the incidence of bcl-2 rearrangement in blood and marrow in a cohort of patients systematically investigated at diagnosis, to describe the correlation between bcl-2 and presenting features, to clarify the correlation of molecular response with outcome. Of 98 patients studied at initial staging for the presence of bcl-2 rearrangement, 64 (65%) showed bcl-2/IgH rearrangement in peripheral blood (PB) and/or bone marrow (BM) (58 at Major Breakpoint Region, MBR, and 6 at minor cluster region, mcr) while no bcl-2/IgH rearrangement was detected in the remaining 34 (35%) (germline status). No statistically significant differences were found between bcl-2 positive and bcl-2 negative cases as concerns presenting clinical features and response to first-line therapy. The median event-free survival, EFS, was not reached for the bcl-2 negative patients in PB and was 11 months for bcl-2 positive patients (statistically significant, P = 0.01) and, similarly, the median EFS was not reached for the bcl-2 negative patients in BM and was 11 months for bcl-2 positive patients (statistically significant, P = 0.04). Of the 64 bcl-2 positive cases, patients were analysed for molecular response (48 in BM and 40 in PB): 16 were molecular responders in BM and 20 were molecular responders in PB. The median EFS was 19 months for molecular responders in PB and 9 months for non-responders; 1-year-EFS was 68% (95% CI; 49 - 88), for responders in PB and 42% (95% CI; 22 - 61) for non-responders (P = 0.05). The median EFS was 11 months both for molecular responders and non-responders in BM; 1-year-EFS was 52% for responders in BM (CI; 30 - 73), and 43% (CI 33 - 71) for non-responders (P = 0.7). No clinical feature showed significant correlation with PB and BM molecular responses. This analysis shows that bcl-2 rearrangement in blood and bone marrow is frequently detected at staging, even in stage I disease. Absence of the bcl-2 rearrangement is related to a better EFS and the achievement of a molecular response in peripheral blood after therapy is associated with a better EFS.

Splenic marginal zone lymphoma: a prognostic model for clinical use.

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100,000/microL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (x 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient.

Correlation of the FLIPI score for follicular lymphoma with period of diagnosis and type of treatment.

OBJECTIVES: Follicular lymphoma (FL) is generally considered an indolent disorder but a significant subset of patients shows a worse outcome. Aim of this study was to validate the FLIPI score in an independent series of follicular lymphoma patients and to correlate prognostic categories with the period of diagnosis and the use of anthracycline. METHODS: We evaluated the clinical characteristics, prognostic stratification, and outcome of 338 patients with follicular lymphoma consecutively diagnosed and followed at our Institution between 1975 and 2002. RESULTS: The distribution of patients within the prognostic categories of the IPI and FLIPI score, while confirming the indolent outcome of follicular lymphoma, shows that a subset of patients has a worse prognosis. With the IPI score, 62% of patients are in the low risk, 26% in the low-intermediate, and 12% in the high (high-intermediate+high) risk group. With the FLIPI score, 48% of patients are categorized as low risk, 31% as intermediate risk, and 21% as poor risk. With the IPI score, median OS is 17.3 years for the low risk; 6.3 for the intermediate risk, and 5.2 years for the high risk group (p=0.0004). With the FLIPI system, median OS is 15.5 years for the low risk, 8.3 years for the intermediate risk, and 5.2 for the poor risk group (p=0.0002). Prognostic scores were calculated also after dividing patients according to the time of diagnosis: in three periods (before 1987, between 1988 and 1997, and from 1998), as well as in two periods (before and after 1998). In all the periods studied survival of patients classified according to IPI and FLIPI categories was significantly different. CONCLUSION: This study shows in an independent series that the FLIPI score is a reproducible prognostic index of clinical utility for the initial assessment of patients with follicular lymphoma.

Combination of rituximab, cyclophosphamide, and vincristine induces complete hematologic remission of splenic marginal zone lymphoma.

Optimal treatment for splenic marginal zone lymphoma (MZL) is not clearly established. Splenectomy has been proposed as the treatment of choice in patients with cytopenias and/or symptoms caused by an enlarged spleen. Splenic MZL, which expresses the CD20 antigen on tumor cell surfaces, is a disease entity candidate to treatment with anti-CD20 monoclonal antibodies. We employed an immunochemotherapy regimen with rituximab/cyclophosphamide/vincristine in 3 patients with splenic MZL who had only a partial response following CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) or CHOP-like therapy. The immunochemotherapy regimen was well tolerated and all patients exhibited complete remission. To our knowledge, this is the first report of splenic MZL showing response to a combination of rituximab with chemotherapy.