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P056 International prognostic index, bulky disease, Ki67, bcl-2 and the outcome in newly diagnosed patients with diffuse large B cell lymphoma
Poster Sessions Conclusion: Expression of CD10+ in DLBCL has prognostic significance in association to response rate in first line DLBCL. In future prospective study, on higher number of patients, influence of CD10+ in DLBCL prognosis in association with RR, RFS and OS should be determined.
P054 Clinical and morphological characteristics of non-Hodgkin’s lymphomas I. Poddubnaya, A. Babkina, B. Toloknov, I. Poddubnaya. Moscow, Russia Aim: The aim of the study was comparison of the clinical and morphological features primary and secondary nonHodgkin’s lymphomas (NHL) of female reproductive system (FRS) - 23 cases. Patients and methods: In Cancer Research Center of RAMS from 1989 till 2005- 321 patients with extranodal NHL were observed. Results: The FRS lesion was found in 8 cases: cervix uteri- 4 cases, breast- 2 cases, 1 cases- vagina and ovaries -1 case. 6/8 cases were defined as aggressive variant NHL (diffuse large B-cell lymphoma-5 and Berkitt’s lymphoma-1); only in 2/8 cases was indolent follicular lymphoma (II type). Middle age of patients was 52 years. According to An-Arbor classification 6/8 women had IIA stage, 2/8 -I stage. IPI in all 8 cases defined as good. LDG level exceeded discriminative only in 2/8 cases. Treatment was effective in all pts: CR was determined in 7 of 8 pts (duration 3-10 years). 15 cases of secondary NHL of FRS were defind as aggressive type of NHL with breast and ovaries lesion. Middle age in this group of patients was 39 years. IPI was definded as poor in all cases. Complete remission after treatment was reached only in 2 of 15 cases. Conclusion: Extranodal non- Hodgkin’s lymphomas of female reproductive system, both primary and secondary, are rare disease. Primary lesion is more typical for older women, secondary - mainly affecting younger women (in reproductive period). Chemotherapy response and prognosis are better in primary FRSNHL.
P055 Clinical and morphological characteristics of non-Hodgkin’s lymphomas A.V. Babkina, B.O. Toloknov, I. Poddubnaya. Moscow, Russia Aim: The aim of the study was comparison of the clinical and morphological features primary and secondary nonHodgkin’s lymphomas (NHL) of female reproductive system (FRS) - 23 cases. Patients and methods: In Cancer Research Center of RAMS from 1989 till 2005- 321 patients with extranodal NHL were observed. The FRS lesion was found in 8 cases: cervix uteri - 4 cases, breast - 2 cases, 1 cases - vagina and ovaries -
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1 case. 6/8 cases were defined as aggressive variant NHL (diffuse large B-cell lymphoma-5 and Berkitt’s lymphoma-1); only in 2/8 cases was indolent follicular lymphoma (II type). Middle age of patients was 52 years. According to An-Arbor classification 6/8 women had IIA stage, 2/8 - I stage. IPI in all 8 cases defined as good. LDG level exceeded discriminative only in 2/8 cases. Treatment was effective in all pts: CR was determined in 7 of 8 pts (duration 3-10 years). Results: 15 cases of secondary NHL of FRS were defind as aggressive type of NHL with breast and ovaries lesion. Middle age in this group of patients was 39 years. IPI was definded as poor in all cases. Complete remission after treatment was reached only in 2 of 15 cases. Conclusion: Extranodal non- Hodgkin’s lymphomas of female reproductive system, both primary and secondary, are rare disease. Primary lesion is more typical for older women, secondary - mainly affecting younger women (in reproductive period). Chemotherapy response and prognosis are better in primary FRSNHL.
P056 International prognostic index, bulky disease, Ki67, bcl-2 and the outcome in newly diagnosed patients with diffuse large B cell lymphoma M. Perunicic Jovanovic, L. Jakovic, B. Mihaljevic, A. Bogdanovic, B. Andjelic, A. Sretenovic, S. Jankovic, D. Boskovic. Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia, Newly diagnosed patients with Diffuse large B cell lymphoma (DLBCL) treated with immunochemotherapy have durable remissions and improved overall survival. Still it is important to initially identify high risk patients (pts) who may benefit from even more effective therapies. Aim: The aim of the study was to determine the prognostic value of clinical and molecular parameters in pts with DLBCL. Their significance was evaluated regarding response to treatment and survival period. Patients and methods: Retrospective analysis was performed in 50 DLBCL pts (30 male/20 female, mean age 50±18.16 years, range 17-80) who were treated with rituximab plus CHOP. Follow up period was 62 months. On presentation International Prognostic Index (IPI) and bulky disease were determined in all pts. Staining for bcl-2 and Ki-67 was performed on paraffinembedded sections using an indirect immunoperoxidase method and a specific monoclonal antibody. We analyzed the percentage of neoplastic cells with Ki67+ nuclear staining on 10 different high power microscopy fields (HPF, 400x). The intensity of these staining was graded as weak (0-30% Ki-67+), moderate (31-60% Ki-67+ cells), and strong (>60% Ki67+ cells). Tumors were considered positive (+) when at least 50% of tumor cells expressed bcl-2 protein. Results: After 5 years of follow-up, 28 (56%) pts are still in complete remission (CR) and 22 (44%) pts died. Extra-
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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
P054 Clinical and morphological characteristics of non-Hodgkin’s lymphomas I. Poddubnaya, A. Babkina, B. Toloknov, I. Poddubnaya. Moscow, Russia Aim: The aim of the study was comparison of the clinical and morphological features primary and secondary nonHodgkin’s lymphomas (NHL) of female reproductive system (FRS) - 23 cases. Patients and methods: In Cancer Research Center of RAMS from 1989 till 2005- 321 patients with extranodal NHL were observed. Results: The FRS lesion was found in 8 cases: cervix uteri- 4 cases, breast- 2 cases, 1 cases- vagina and ovaries -1 case. 6/8 cases were defined as aggressive variant NHL (diffuse large B-cell lymphoma-5 and Berkitt’s lymphoma-1); only in 2/8 cases was indolent follicular lymphoma (II type). Middle age of patients was 52 years. According to An-Arbor classification 6/8 women had IIA stage, 2/8 -I stage. IPI in all 8 cases defined as good. LDG level exceeded discriminative only in 2/8 cases. Treatment was effective in all pts: CR was determined in 7 of 8 pts (duration 3-10 years). 15 cases of secondary NHL of FRS were defind as aggressive type of NHL with breast and ovaries lesion. Middle age in this group of patients was 39 years. IPI was definded as poor in all cases. Complete remission after treatment was reached only in 2 of 15 cases. Conclusion: Extranodal non- Hodgkin’s lymphomas of female reproductive system, both primary and secondary, are rare disease. Primary lesion is more typical for older women, secondary - mainly affecting younger women (in reproductive period). Chemotherapy response and prognosis are better in primary FRSNHL.
P055 Clinical and morphological characteristics of non-Hodgkin’s lymphomas A.V. Babkina, B.O. Toloknov, I. Poddubnaya. Moscow, Russia Aim: The aim of the study was comparison of the clinical and morphological features primary and secondary nonHodgkin’s lymphomas (NHL) of female reproductive system (FRS) - 23 cases. Patients and methods: In Cancer Research Center of RAMS from 1989 till 2005- 321 patients with extranodal NHL were observed. The FRS lesion was found in 8 cases: cervix uteri - 4 cases, breast - 2 cases, 1 cases - vagina and ovaries -
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1 case. 6/8 cases were defined as aggressive variant NHL (diffuse large B-cell lymphoma-5 and Berkitt’s lymphoma-1); only in 2/8 cases was indolent follicular lymphoma (II type). Middle age of patients was 52 years. According to An-Arbor classification 6/8 women had IIA stage, 2/8 - I stage. IPI in all 8 cases defined as good. LDG level exceeded discriminative only in 2/8 cases. Treatment was effective in all pts: CR was determined in 7 of 8 pts (duration 3-10 years). Results: 15 cases of secondary NHL of FRS were defind as aggressive type of NHL with breast and ovaries lesion. Middle age in this group of patients was 39 years. IPI was definded as poor in all cases. Complete remission after treatment was reached only in 2 of 15 cases. Conclusion: Extranodal non- Hodgkin’s lymphomas of female reproductive system, both primary and secondary, are rare disease. Primary lesion is more typical for older women, secondary - mainly affecting younger women (in reproductive period). Chemotherapy response and prognosis are better in primary FRSNHL.
P056 International prognostic index, bulky disease, Ki67, bcl-2 and the outcome in newly diagnosed patients with diffuse large B cell lymphoma M. Perunicic Jovanovic, L. Jakovic, B. Mihaljevic, A. Bogdanovic, B. Andjelic, A. Sretenovic, S. Jankovic, D. Boskovic. Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia, Newly diagnosed patients with Diffuse large B cell lymphoma (DLBCL) treated with immunochemotherapy have durable remissions and improved overall survival. Still it is important to initially identify high risk patients (pts) who may benefit from even more effective therapies. Aim: The aim of the study was to determine the prognostic value of clinical and molecular parameters in pts with DLBCL. Their significance was evaluated regarding response to treatment and survival period. Patients and methods: Retrospective analysis was performed in 50 DLBCL pts (30 male/20 female, mean age 50±18.16 years, range 17-80) who were treated with rituximab plus CHOP. Follow up period was 62 months. On presentation International Prognostic Index (IPI) and bulky disease were determined in all pts. Staining for bcl-2 and Ki-67 was performed on paraffinembedded sections using an indirect immunoperoxidase method and a specific monoclonal antibody. We analyzed the percentage of neoplastic cells with Ki67+ nuclear staining on 10 different high power microscopy fields (HPF, 400x). The intensity of these staining was graded as weak (0-30% Ki-67+), moderate (31-60% Ki-67+ cells), and strong (>60% Ki67+ cells). Tumors were considered positive (+) when at least 50% of tumor cells expressed bcl-2 protein. Results: After 5 years of follow-up, 28 (56%) pts are still in complete remission (CR) and 22 (44%) pts died. Extra-
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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