The t(14;18) translocation is a highly consistent feature of follicular lymphoma although the und... more The t(14;18) translocation is a highly consistent feature of follicular lymphoma although the underlying mechanism generating this fusion remains uncertain. The breakpoints on chromosome 18 are at one of two sites, designated mbr and mcr, in the bcl-2 gene. A polymerase chain reaction strategy has been developed for amplification and direct sequencing of the resultant 14q+ and 18q- reciprocal junctions. Sequence analysis of the amplified 14q+ junction established that 21 tumours contained a bcl-2 (mbr) sequence to an immunoglobulin JH region, the majority being J5 or J6. A nonrandom pattern of breakpoints within the mbr region was found. Clustering of the breakpoint occurred with over 60% of the translocations clustering within 10 bases. There was a second cluster within the mbr 50 bases 3' of the first cluster. One of these junctions had an unusual configuration with the bcl-2 and JH sequences separated by a recognisable DH region. This suggests that at least some of the junctional sequences, previously thought of as N insertions, may be fragments of unrecognised DH regions. In one of these tumours it was possible to sequence the reciprocal 18q- junction, showing it to consist of a DH/bcl-2 (mbr) fusion. Analysis of both reciprocal junctions for a translocation in the mcr region of bcl-2, showed that this 18q- junction also consisted of DH fused to a bcl-2 sequence. In contrast to previous analyses, which demonstrated either loss or duplication of bcl-2 sequences at the breakpoints, the bcl-2 sequence was conserved during the mbr and mcr translocations in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
Follicular lymphoma (FL) is considered an indolent but incurable disease. It remains to be clarif... more 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.
To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell... more To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL). A retrospective international survey of 373 patients with primary testicular DLCL. Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy. Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.
The t(14;18) translocation is a highly consistent feature of follicular lymphoma although the und... more The t(14;18) translocation is a highly consistent feature of follicular lymphoma although the underlying mechanism generating this fusion remains uncertain. The breakpoints on chromosome 18 are at one of two sites, designated mbr and mcr, in the bcl-2 gene. A polymerase chain reaction strategy has been developed for amplification and direct sequencing of the resultant 14q+ and 18q- reciprocal junctions. Sequence analysis of the amplified 14q+ junction established that 21 tumours contained a bcl-2 (mbr) sequence to an immunoglobulin JH region, the majority being J5 or J6. A nonrandom pattern of breakpoints within the mbr region was found. Clustering of the breakpoint occurred with over 60% of the translocations clustering within 10 bases. There was a second cluster within the mbr 50 bases 3' of the first cluster. One of these junctions had an unusual configuration with the bcl-2 and JH sequences separated by a recognisable DH region. This suggests that at least some of the junctional sequences, previously thought of as N insertions, may be fragments of unrecognised DH regions. In one of these tumours it was possible to sequence the reciprocal 18q- junction, showing it to consist of a DH/bcl-2 (mbr) fusion. Analysis of both reciprocal junctions for a translocation in the mcr region of bcl-2, showed that this 18q- junction also consisted of DH fused to a bcl-2 sequence. In contrast to previous analyses, which demonstrated either loss or duplication of bcl-2 sequences at the breakpoints, the bcl-2 sequence was conserved during the mbr and mcr translocations in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
Follicular lymphoma (FL) is considered an indolent but incurable disease. It remains to be clarif... more 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.
To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell... more To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL). A retrospective international survey of 373 patients with primary testicular DLCL. Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy. Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.
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