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P058 Modified NHL-BFM-90 program in primary gastric diffuse large B-cell lymphoma (PGDLBCL) with adverse prognostic factors
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Poster Sessions
nodal disease, bulky form, and existence of B symptoms had certain influence on overall survival (OS) and event free survival (EFS) but these differences were not statistically significant (log rank, p>0.05). Univariate survival analysis showed that high IPI had statistically significant negative influence on overall and also on event free survival time (log rank, p<0.01). The Log rank test analysis signified that pts with a high proliferative fraction (Ki67>60%) had worse (OS5y) of 40% compared to those with low proliferation (Ki67<60%) with OS5y of 80% (p<0.01). There was a clear difference in achievement of complete remission between pts bcl-2 positive and negative (66% vs 86%, p<0.05). In survival analysis, bcl-2 negative pts (<50% of bcl-2+ tumor cells) had significantly higher OS5y 68% compared to those bcl-2 positive (>50% of bcl-2+ tumor cells) with OS5y 37% (p<0.05). Multivariate analysis performed by Cox’s model revealed that IPI>3, high Ki-67+ (at a threshold of 60% of positive cells), bcl-2 positivity (threshold 50%) had a significant independent prognostic value concerning overall survival (p<0.05). Conclusion: Initial high IPI score associated with high Ki67+ and bcl-2+ could represent possible predictive factors of poor prognosis, which will help identifying high risk subgroup of newly diagnosed pts with DLBCL.
P057 Roles of flow cytometry in bone marrow staging of B-cell non-Hodgkin lymphoma C. Na Nakorn, T. Polprasert, J. Srisakham, T. Assanasen. Division of Hematology, Department of Medicine and Department of Patology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: Bone marrow staging is important in determining the extent of disease and for making therapeutic decision in B-cell non-Hodgkin lymphoma (B-NHL). Flow cytometry has been widely used in this setting but its value has not been clearly demonstrated. Objectives: To determine the usefulness of bone marrow flow cytometry in staging of B-NHL. Materials and Methods: We compare the results of bone marrow studies using bone marrow aspirate (BMA), bone marrow biopsy (BMB) and three-color flow cytometry (FMC), in non-leukemic B-NHL patients performed during May 2003 to December 2006 at our institution and determine the concordant rate among these three methods in detecting bone marrow involvement by B-NHL. Results: Two hundred and sixty-eight bone marrow samples were analyzed in this study. Diffuse large B-cell lymphoma (DLBCL) was the most common histologic subtype (60.8%). Bone marrow (BM) involvement as confirmed by immunohistochemistry of BMB was observed in 65 samples. Prevalence of BM involvement was slightly higher in indolent B-NHL (32.2%) as compared to aggressive B-NHL (20.2%). Agreement among all three methods was observed in 167 samples (62.3%). BMA had the sensitivity of 78.5% and specificity of
73.8%. FCM alone had the sensitivity of 64.6% and specificity of 89.6%. FCM failed to demonstrate clonal B-cells mainly in patients with focal involvement pattern. When FCM was combined with BMA, the sensitivity was increased to 89.2% but the specificity was decreased to 68%. This performed worse than using morphological criteria in BMB alone, which showed sensitivity of 90.7% and specificity of 95%. Conclusion: Based on these data, we conclude that flow cytometry may not be necessary in bone marrow staging of B-NHL in patients with non-leukemic presentation.
P058 Modified NHL-BFM-90 program in primary gastric diffuse large B-cell lymphoma (PGDLBCL) with adverse prognostic factors E. Zvonkov, E. Baryakh, B. Krasilnikova, A. Magomedova, A. Gubkin, S. Kravchenko, A. Kremenetskaya, A. Vorobjev. Department of oncohematology, N.N. Blokhin’s Russian Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russia CHOP chemotherapy can induce complete responses (CR) in up to 80% of patients PGDLBCL but the presence of unfavorable prognostic factors (male sex; bulky disease; stage > IE; B-symptoms; elevated LDH; high proliferation rate) decrease the efficacy of this therapy. Optimal therapy of these lymphomas is controversial. Aim: Efficacy and safety assessment of the modified chemotherapy scheme NHL-BFM-90 in treatment adult PGDLBCL with adverse prognostic factors. Patients and methods: Nine patients PGDLBCL with adverse prognostic factors underwent modified NHL-BFM-90 chemotherapy between January 2004 and December 2006. The following clinical information was obtained: age, sex, site of tumor, B-symptoms, LDH level, stage, morphology, therapy and duration of follow-up. The type of lymphoma was classified according to the WHO classification system. For staging, a modification of the Ann Arbor system, proposed Musshoff, was used. The NHL-BFM-90 program (blocks A and B) was modified for adults in the following way: methotrexate (1 g/m2 i/v during 12 hours) was used and leucovorine was administrated in 18 hours after the beginning of methotrexate infusion. Doxorubicin (50 mg/m2 ) was added on the third day of block A. Results: There were 6 women and 3 men. The mean age at presentation was 53 years (30 -73 ys), 2 pts were older than 60. Nine pts had tumor-related pain, 6 pts - Â-symptoms, 2 pts - pyloric stenosis and 2 pts - elevated LDH level. Gastric endoscopy revealed massive ulcerative infiltration of distal stomach portion more than 10 cm in size in all pts. The stages of disease were IE- 1 pt, IIE -7 pts, IV- 1 pt (stomach + tonsil). Diagnosis of diffuse large B-cell lymphoma was proved by endoscopic gastric biopsy with subsequent histological assay and immunohistochemistry. Proliferate rate of tumor cells was measured by nuclear Ki-67 expression and
Poster Sessions ranged from 70 to 100% in all patients. C-myc translocation was assessed for exclusion of Burkitt’s lymphoma. All pts received modified NHL-BFM-90 program as a first line of therapy. None patients received operative treatment. Altogether 33 blocks (A and B) of the modified chemotherapy program were applied (2-6, mean 4). Hem atologic toxity of grade 3 and 4 was observed in all pts, but fatal infectious complications, associated with chemotherapy were not registered. Acute reversible renal failure after 2 blocks in 2 cases and hepatitis virus B reactivation in 1 case became the reason for subsequent switch to ÑÍÎÐ therapy. All pts achieved a CR after two blocks. The mean follow-up is 24 month (range 1-33). No relapses have been registered so far. Radiotherapy was not used. Conclusion: NHL-BFM-90 chemotherapy has shown substantial activity in adult pts with PGDLBCL, especially in prognostically unfavorable cases. The number of cycles must be decreased, especially in cases with rapid response achievement.
Lymphoma II P059 Long-term results of CHOP/CHOP like chemotherapy ± rituximab in patients with diffuse large B-cell lymphoma (DLBCL) B. Mihaljevic, S. Sretenovic, S. Jankovic, B. Andjelic, L. Jakovic, B. Milicic, J. Bila, V. Milosevic, A. Sretenovic, M. Perunicic, M. Petrovic. Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia CHOP regimen was the gold therapy standard in newly diagnosed pts with DLBCL. With introducing of anti CD20 monoclonal Ab-rituximab, the overal survival was significantly improved. Aim: The aim of the study was to compare rituximab plus CHOP/CHOP like chemotherapy with CHOP/CHOP like regimens alone according to response rate and overall survival. Patients and methods: In all pts, initial International Prognostic Index (IPI), B symptomatology, bulky disease, RBC sedimentation rate, serum albumin and beta-2 microglobulin were determined. Fifty pts were treated with CHOP or EPOCH regimen, and 69 with rituximab plus CHOP/EPOH regimen. The median follow up was 79 months. Results: For the whole group of pts, the mean age was 53.95±16.71 yrs, range 21-81 (60.5% of pts were <60 yrs). Gender distribution was 61 male/58 female. The IPI score was as follows: low 23.5%, low intermediate 31.1% and high intermediate in 10.9% of pts. Bulky disease had 26.9%, LDH level was increased in 55.5% pts. The 5 yrs overall survival was significantly higher in pts without B symptoms (93.6% vs.43.55%, p=0,0008), in pts with LDH<450 (78.95% vs. 41.33%, p=0,0437) and in pts with CS I,II (90.12% vs. 44.65%, p=0,0002). The complete response in
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patients treated with immunochemotherapy is significantly higher than in the patients treated with chemotherapy alone (87% vs 66%, p= 0,006, log rank test). The 5 yrs survival probability was significantly higher in pts treated with immunochemotherapy: 78.88% vs 43.68% (p= 0.002, log-rank test). No long-term toxicity appeared to be associated with R-CHOP or R-EPOCH combination regimens. Conclusion: Using the combination of R- CHOP/EPOCH leads to significant improvement of the outcome of newly diagnosed pts with DLBCL with significant 5 year survival benefit. Having in mind that IPI and age adjusted IPI, as well as bulky disease didn’t have influence on survival in our group of pts, we think that the introduction of a new scoring system for survival probability should be considered.
P060 The influence of international prognostic score and bulky disease in patients with primary mediastinal B sclerosing lymphoma treated with immunochemotherapy B. Mihaljevic, B. Andjelic, L. Jakovic, S. Jankovic, A. Sretenovic, J. Bila, M. Mitrovic, V. Milosevic, M. Perunicic, S. Solujic, B. Milicic, M. Petrovic, D. Boskovic. Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia Primary mediastinal B sclerosing lymphoma (PMBL) is a subtype of the diffuse large B-cell lymphoma (DLBCL), which is, based on its frequency, the second most frequent mediastinal neoplasm. The tumor is frequent in women in the third and fourth decades of their life and the tumor is manifested as a large intrathoracic mass located in the anterior mediastinum with dyspnea, cough, superior vena cava syndrome, pleural and/or pericardial effusion. With conventional therapy, the prognosis is less favorable then in DLBCL-GC. Aim: The aim was to determine correlation of IPI and bulky disease with patinet’s outcome in this relatively rare DLBCL subtypes. Patients and methods: Thirty seven newly diagnosed patients were treated with immunochemotherapy (rituximab plus EPOCH or MACOP B regimens). The median follow up was 57 months. Results: There was no statistical difference among the pts with or without bulky disease on presentation. However, there was a trend of better survival in patients without bulky disease (3 yrs OS 80.72% vs 66,3%). According to IPI score, there was no difference between the subgroups but the 3 yrs OS in patients with high intermediate and high IPI was shorter then in the whole group (55.56% vs 73.82%). Conclusion: The immunochemoptherapy is an effective treatment for pts with PMBL. However, in our study IPI and bulky disease didn’t show prognostic significance and more sophisticated prognostic parameters should be evaluated.
Poster Sessions
nodal disease, bulky form, and existence of B symptoms had certain influence on overall survival (OS) and event free survival (EFS) but these differences were not statistically significant (log rank, p>0.05). Univariate survival analysis showed that high IPI had statistically significant negative influence on overall and also on event free survival time (log rank, p<0.01). The Log rank test analysis signified that pts with a high proliferative fraction (Ki67>60%) had worse (OS5y) of 40% compared to those with low proliferation (Ki67<60%) with OS5y of 80% (p<0.01). There was a clear difference in achievement of complete remission between pts bcl-2 positive and negative (66% vs 86%, p<0.05). In survival analysis, bcl-2 negative pts (<50% of bcl-2+ tumor cells) had significantly higher OS5y 68% compared to those bcl-2 positive (>50% of bcl-2+ tumor cells) with OS5y 37% (p<0.05). Multivariate analysis performed by Cox’s model revealed that IPI>3, high Ki-67+ (at a threshold of 60% of positive cells), bcl-2 positivity (threshold 50%) had a significant independent prognostic value concerning overall survival (p<0.05). Conclusion: Initial high IPI score associated with high Ki67+ and bcl-2+ could represent possible predictive factors of poor prognosis, which will help identifying high risk subgroup of newly diagnosed pts with DLBCL.
P057 Roles of flow cytometry in bone marrow staging of B-cell non-Hodgkin lymphoma C. Na Nakorn, T. Polprasert, J. Srisakham, T. Assanasen. Division of Hematology, Department of Medicine and Department of Patology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: Bone marrow staging is important in determining the extent of disease and for making therapeutic decision in B-cell non-Hodgkin lymphoma (B-NHL). Flow cytometry has been widely used in this setting but its value has not been clearly demonstrated. Objectives: To determine the usefulness of bone marrow flow cytometry in staging of B-NHL. Materials and Methods: We compare the results of bone marrow studies using bone marrow aspirate (BMA), bone marrow biopsy (BMB) and three-color flow cytometry (FMC), in non-leukemic B-NHL patients performed during May 2003 to December 2006 at our institution and determine the concordant rate among these three methods in detecting bone marrow involvement by B-NHL. Results: Two hundred and sixty-eight bone marrow samples were analyzed in this study. Diffuse large B-cell lymphoma (DLBCL) was the most common histologic subtype (60.8%). Bone marrow (BM) involvement as confirmed by immunohistochemistry of BMB was observed in 65 samples. Prevalence of BM involvement was slightly higher in indolent B-NHL (32.2%) as compared to aggressive B-NHL (20.2%). Agreement among all three methods was observed in 167 samples (62.3%). BMA had the sensitivity of 78.5% and specificity of
73.8%. FCM alone had the sensitivity of 64.6% and specificity of 89.6%. FCM failed to demonstrate clonal B-cells mainly in patients with focal involvement pattern. When FCM was combined with BMA, the sensitivity was increased to 89.2% but the specificity was decreased to 68%. This performed worse than using morphological criteria in BMB alone, which showed sensitivity of 90.7% and specificity of 95%. Conclusion: Based on these data, we conclude that flow cytometry may not be necessary in bone marrow staging of B-NHL in patients with non-leukemic presentation.
P058 Modified NHL-BFM-90 program in primary gastric diffuse large B-cell lymphoma (PGDLBCL) with adverse prognostic factors E. Zvonkov, E. Baryakh, B. Krasilnikova, A. Magomedova, A. Gubkin, S. Kravchenko, A. Kremenetskaya, A. Vorobjev. Department of oncohematology, N.N. Blokhin’s Russian Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russia CHOP chemotherapy can induce complete responses (CR) in up to 80% of patients PGDLBCL but the presence of unfavorable prognostic factors (male sex; bulky disease; stage > IE; B-symptoms; elevated LDH; high proliferation rate) decrease the efficacy of this therapy. Optimal therapy of these lymphomas is controversial. Aim: Efficacy and safety assessment of the modified chemotherapy scheme NHL-BFM-90 in treatment adult PGDLBCL with adverse prognostic factors. Patients and methods: Nine patients PGDLBCL with adverse prognostic factors underwent modified NHL-BFM-90 chemotherapy between January 2004 and December 2006. The following clinical information was obtained: age, sex, site of tumor, B-symptoms, LDH level, stage, morphology, therapy and duration of follow-up. The type of lymphoma was classified according to the WHO classification system. For staging, a modification of the Ann Arbor system, proposed Musshoff, was used. The NHL-BFM-90 program (blocks A and B) was modified for adults in the following way: methotrexate (1 g/m2 i/v during 12 hours) was used and leucovorine was administrated in 18 hours after the beginning of methotrexate infusion. Doxorubicin (50 mg/m2 ) was added on the third day of block A. Results: There were 6 women and 3 men. The mean age at presentation was 53 years (30 -73 ys), 2 pts were older than 60. Nine pts had tumor-related pain, 6 pts - Â-symptoms, 2 pts - pyloric stenosis and 2 pts - elevated LDH level. Gastric endoscopy revealed massive ulcerative infiltration of distal stomach portion more than 10 cm in size in all pts. The stages of disease were IE- 1 pt, IIE -7 pts, IV- 1 pt (stomach + tonsil). Diagnosis of diffuse large B-cell lymphoma was proved by endoscopic gastric biopsy with subsequent histological assay and immunohistochemistry. Proliferate rate of tumor cells was measured by nuclear Ki-67 expression and
Poster Sessions ranged from 70 to 100% in all patients. C-myc translocation was assessed for exclusion of Burkitt’s lymphoma. All pts received modified NHL-BFM-90 program as a first line of therapy. None patients received operative treatment. Altogether 33 blocks (A and B) of the modified chemotherapy program were applied (2-6, mean 4). Hem atologic toxity of grade 3 and 4 was observed in all pts, but fatal infectious complications, associated with chemotherapy were not registered. Acute reversible renal failure after 2 blocks in 2 cases and hepatitis virus B reactivation in 1 case became the reason for subsequent switch to ÑÍÎÐ therapy. All pts achieved a CR after two blocks. The mean follow-up is 24 month (range 1-33). No relapses have been registered so far. Radiotherapy was not used. Conclusion: NHL-BFM-90 chemotherapy has shown substantial activity in adult pts with PGDLBCL, especially in prognostically unfavorable cases. The number of cycles must be decreased, especially in cases with rapid response achievement.
Lymphoma II P059 Long-term results of CHOP/CHOP like chemotherapy ± rituximab in patients with diffuse large B-cell lymphoma (DLBCL) B. Mihaljevic, S. Sretenovic, S. Jankovic, B. Andjelic, L. Jakovic, B. Milicic, J. Bila, V. Milosevic, A. Sretenovic, M. Perunicic, M. Petrovic. Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia CHOP regimen was the gold therapy standard in newly diagnosed pts with DLBCL. With introducing of anti CD20 monoclonal Ab-rituximab, the overal survival was significantly improved. Aim: The aim of the study was to compare rituximab plus CHOP/CHOP like chemotherapy with CHOP/CHOP like regimens alone according to response rate and overall survival. Patients and methods: In all pts, initial International Prognostic Index (IPI), B symptomatology, bulky disease, RBC sedimentation rate, serum albumin and beta-2 microglobulin were determined. Fifty pts were treated with CHOP or EPOCH regimen, and 69 with rituximab plus CHOP/EPOH regimen. The median follow up was 79 months. Results: For the whole group of pts, the mean age was 53.95±16.71 yrs, range 21-81 (60.5% of pts were <60 yrs). Gender distribution was 61 male/58 female. The IPI score was as follows: low 23.5%, low intermediate 31.1% and high intermediate in 10.9% of pts. Bulky disease had 26.9%, LDH level was increased in 55.5% pts. The 5 yrs overall survival was significantly higher in pts without B symptoms (93.6% vs.43.55%, p=0,0008), in pts with LDH<450 (78.95% vs. 41.33%, p=0,0437) and in pts with CS I,II (90.12% vs. 44.65%, p=0,0002). The complete response in
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patients treated with immunochemotherapy is significantly higher than in the patients treated with chemotherapy alone (87% vs 66%, p= 0,006, log rank test). The 5 yrs survival probability was significantly higher in pts treated with immunochemotherapy: 78.88% vs 43.68% (p= 0.002, log-rank test). No long-term toxicity appeared to be associated with R-CHOP or R-EPOCH combination regimens. Conclusion: Using the combination of R- CHOP/EPOCH leads to significant improvement of the outcome of newly diagnosed pts with DLBCL with significant 5 year survival benefit. Having in mind that IPI and age adjusted IPI, as well as bulky disease didn’t have influence on survival in our group of pts, we think that the introduction of a new scoring system for survival probability should be considered.
P060 The influence of international prognostic score and bulky disease in patients with primary mediastinal B sclerosing lymphoma treated with immunochemotherapy B. Mihaljevic, B. Andjelic, L. Jakovic, S. Jankovic, A. Sretenovic, J. Bila, M. Mitrovic, V. Milosevic, M. Perunicic, S. Solujic, B. Milicic, M. Petrovic, D. Boskovic. Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia Primary mediastinal B sclerosing lymphoma (PMBL) is a subtype of the diffuse large B-cell lymphoma (DLBCL), which is, based on its frequency, the second most frequent mediastinal neoplasm. The tumor is frequent in women in the third and fourth decades of their life and the tumor is manifested as a large intrathoracic mass located in the anterior mediastinum with dyspnea, cough, superior vena cava syndrome, pleural and/or pericardial effusion. With conventional therapy, the prognosis is less favorable then in DLBCL-GC. Aim: The aim was to determine correlation of IPI and bulky disease with patinet’s outcome in this relatively rare DLBCL subtypes. Patients and methods: Thirty seven newly diagnosed patients were treated with immunochemotherapy (rituximab plus EPOCH or MACOP B regimens). The median follow up was 57 months. Results: There was no statistical difference among the pts with or without bulky disease on presentation. However, there was a trend of better survival in patients without bulky disease (3 yrs OS 80.72% vs 66,3%). According to IPI score, there was no difference between the subgroups but the 3 yrs OS in patients with high intermediate and high IPI was shorter then in the whole group (55.56% vs 73.82%). Conclusion: The immunochemoptherapy is an effective treatment for pts with PMBL. However, in our study IPI and bulky disease didn’t show prognostic significance and more sophisticated prognostic parameters should be evaluated.