Incidence, risk factors and outcome of histological transformation in follicular lymphoma.

Histological transformation (HT) into diffuse large B-cell lymphoma (DLBCL) was documented in 37 of the 281 (13%; 95% CI, 9-18) follicular lymphoma (FL) patients treated at our institute from 1979 to 2007. HT occurred at a median of 2·75 years from initial FL diagnosis and HT rate was 15% at 10 years and 26% at 14 years, with a plateau from that point onward. Patients with bulky or extranodal disease, or those diagnosed before 1990 had a significantly higher risk of HT. When initial treatment strategies were taken into account, a reduced HT risk was seen in the patients initially managed with a 'watch and wait' policy, while the risk appeared significantly increased in the small subset of 18 patients initially managed with rituximab plus chemotherapy (P = 0·0005). HT was associated with a significantly shorter cause-specific survival (P = 0·0002). Predictors of survival after HT were the Follicular Lymphoma International Prognostic Index at diagnosis, as well as age and performance status at the time of HT. Our data confirm the adverse clinical outcome of FL after HT. In keeping with previous isolated reports, our findings suggest that there is a subgroup of patients in whom HT may not occur.

The development of more than one histologic type of lymphoma in the same patient is frequent and confers a worse prognosis.

BACKGROUND AND OBJECTIVES: Distinct types of lymphoma may develop in the same patient either simultaneously or sequentially. The frequency and clinical significance of this phenomenon are still only partially known. DESIGN AND METHODS: We conducted a retrospective analysis of all cases of lymphomas of different histology occurring in the same patient, denoting these cases as multiple histology lymphoma (MHL). The clinicopathologic characteristics of these cases were compared with those of cases with a single histology (SHL). The histologic classifications were made according to the REAL classification by the same pathologists throughout the study period. RESULTS: MHL were identified in 46 of 347 (13%) consecutive cases of lymphoma diagnosed at a single institution. They presented more frequently in stage III-IV (p=0.008), but the age, sex, and IPI score of patients with MHL did not differ from those of patients with SHL. Small lymphocytic/lymphoplasmacytic subtype was more frequent (16.1% vs 3%, p<0.0001) and Hodgkin's lymphoma (4% vs 16%; p=0.004) less frequent in MHL. Response rates to treatment were similar (85% vs 77.5%), whereas 5-year overall survival was significantly lower for MHL than for SHL (31% vs 67%; p=0.015). Among MHL, 14 cases were diagnosed simultaneously and 32 sequentially, after a median of 18 months. The two subgroups with simultaneous and sequential presentation did not differ in their demographic, clinicopathologic or prognostic characteristics. INTERPRETATION AND CONCLUSIONS: Lymphomas of different histology develop frequently in the same patient, either simultaneously or sequentially. Patients with MHL form a subgroup with few peculiar presenting clinicopathologic features but a markedly worse prognosis, thus warranting prospective biological and clinical studies.

Platelet kinetic study in patients with idiopathic thrombocytopenic purpura (ITP) refractory or relapsing after corticosteroid treatment.

BACKGROUND: A platelet kinetic study (PKS) is not indicated in the evaluation of adult patients with idiopathic thrombocytopenic purpura (ITP) at presentation. However, in ITP patients refractory to or relapsing after corticosteroid therapy, its appropriateness is considered uncertain. METHODS: We prospectively performed a PKS with (111)In oxine-labeled autologous platelets in 93 consecutive adult ITP patients failing steroid treatment. RESULTS: In 22 patients (24%) a primary condition accounting for thrombocytopenia was identified (17 with myelodysplastic syndrome and three aplastic anemia). Non-ITP patients had significantly longer platelet circulating life span (P=0.0001), lower splenic platelet uptake (P=0.008) and higher liver platelet uptake (P=0.05) compared to 71 patients with confirmed ITP. Among ITP patients with platelets persistently <50 x 10(9)/L, splenectomy was considered in 48 cases. In 23 (48%) it was prospectively excluded because of platelet life span > or = 7 days (11 cases), no splenic platelet uptake together with high liver uptake (10 cases), or both conditions (two cases). Splenectomy was successfully carried out in the other 25 patients, obtaining a response rate of 100% (22 complete responses; three partial responses). Persistent relapse occurred in six of 25 (24%) splenectomized patients after a median of three months (range 1-8). PKS parameters were not able to predict post-splenectomy relapse, although relapsed patients had lower splenic/hepatic platelet uptake ratio (2.6 in relapsed vs 4.9 in persistently responsive patients; P=0.08). CONCLUSIONS: It was concluded that in patients with chronic ITP failing steroid therapy, some PKS parameters may be prospectively used to increase the short term success rate of splenectomy.

Frequency of hepatitis B virus mutant in asymptomatic hepatitis B virus carriers receiving prophylactic lamivudine during chemotherapy for hematologic malignancies.

Hepatitis B virus (HBV) reactivation is a potentially fatal complication of chemotherapy in asymptomatic HBV carriers. Prophylactic lamivudine has proven effective for its prevention, but the potential emergence of lamivudine-resistant HBV YMMD mutants, as shown in patients treated for chronic hepatitis, may limit its use. To evaluate the frequency of HBV YMMD mutant and its clinical significance, we have analysed 32 courses of primary lamivudine prophylaxis given to HBV carriers with haematologic malignancies, from the start until 1-5 months after the end of chemotherapy. Lamivudine was used for a median of 6 months (range 2-24+) and median follow-up was 19.5 months (range 5-40). Four episodes of HBV reactivation with mild hepatitis and no evidence of mutant strain occurred after chemotherapy completion and after lamivudine withdrawal. At follow-up YMMD mutant was detected in one patient with normal transaminase levels, who had been on continuous lamivudine for 20 months. In conclusion, among HBV carriers treated with chemotherapy for haematologic malignancies, the emergence of HBV YMMD mutant occurred in 3.1% of prophylactic lamivudine courses and was of little clinical relevance.

Patterns of survival of follicular lymphomas at a single institution through three decades.

Follicular lymphoma (FL) is considered an indolent but incurable disease. It remains to be clarified whether the outcome has changed after the recent introduction of novel treatment modalities. We retrospectively analyzed the outcome of 281 patients with FL treated at the Oncology Institute of Southern Switzerland from 1979 to 2007. Three diagnostic eras were considered, according to the major therapeutic changes: before 1989 ('alkylating agents era', n = 73), 1990 to 1999 ('aggressive regimens and G-CSF era', n = 119), and 2000 to 2007 ('rituximab era', n = 89). The distribution of prognostic factors was similar in the three eras. A significant improvement in cause-specific survival (CSS) was observed over time (p = 0.0088), but not in overall survival. Median CSS was 12.5 years for patients with FL diagnosed before 1989, but was not reached in the more recent groups. The estimated CSS rate at 5 years in the three eras was 80%, 86%, and 91%, respectively. The CSS of patients with FL treated at our institution has improved over the last 25 years. This improvement, already evident before the wide introduction of rituximab in clinical practice, may be a result of the sequential application of effective therapies and improved supportive care.