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P005 Prognostic significance of the different multidrug resistance proteins co-expression in acute myeloid leukemia
Poster Sessions of VB subfamily naïve T cells. The data may provide the feature of severe cellular immunodeficiency in AML patients.
P005 Prognostic significance of the different multidrug resistance proteins co-expression in acute myeloid leukemia O. Zakharov, E. Rybalkina, A. Stavrovskaya, M. Volkova, S. Klimuk, V. Lunin, N. Zhukov. Department of oncohematology, N.N. Blokhin’s Russian Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russia Aim: Conventional induction chemotherapy induces complete remission (CR) in 65-75% of adults with de novo acute myeloid leukemia (AML) only. We investigated the prognostic significance of multidrug resistance proteins (Pglycoprotein (Pgp), BCRP, MRP1 and LRP) expression on AML blast cells with respect to CR achievement. Patients and methods: We included in analysis 42 patients (pts) with de novo AML. Expression of multidrug resistance proteins (MDR) on bone marrow blast cells was evaluated by indirect immunofluorescence and flow cytometry before chemotherapy. Expression of MDR proteins was considered as positive if at least 25% of the blast cells were stained by anti-MDR protein antibody. All pts received standard induction therapy (cytarabine, etoposide and idarubicin or daunorubicine, "3+7+7" regiment). Results: Blast cells was defined as Pgp-positive in 68.3% of cases, BCRP+ in 48.5%, MRP1+ in 56.4%, and LRP+ in 62.9% of cases. After induction therapy 27 (64.3%) pts achieved CR and 15 pts (35.7%) were resistant. MDR proteins expression was observed more frequently in resistant group, then in a sensitive one (71.4% vs 66.6% for Pgp, 62.2% vs 46.6% for MRP1, 71.4% vs 57.14% for LRP, 54.54% vs 45.45% for BCRP, respectively), but the difference was not statistically significant. Expression of all 4 MDR proteins was evaluated in 29 pts. (10 - resistant, 19 - sensitive) Blast cells co-expressed 2-4 MDR proteins in 80% of resistant pts (all studied proteins - 30%, 3 of them - 30% and 2 proteins 20%). In a group of pts achieved CR co-expression of MDR proteins was observed less frequently - 21%. The blast cells expressed 3 proteins in 3 cases only (15.7%), expression of all 4 proteins we observed only in 1 patient (5.3%) with very short CR duration (3 months). Other pts from this group (79%) express only one of the studied proteins. According to chromosome analysis 18.2% of pts with known status of all 4 studied proteins had favorable, 50% - intermediate and 31.8% unfavorable cytogenetic. We didn’t reveal any correlation between the expression of any one MDR protein and cytogenetic prognosis, but the blast cells of all pts in cytogenetically unfavorable group, expressed more then 1 protein (3 or 4 MDR proteins expressed in 71,4% of cases). In favorable and intermediate cytogenetic groups blast cells co-expressed MDR proteins in 25% of cases only (p=0,025). Conclusion: The co-expression of MDR proteins in AML
S67
has a prognostic value with respect to CR achievement in pts receiving standard antracycline-Ara-C regimens. The detection of any single protein didn’t have prognostic significance, only co-expression of 2 and more proteins predict unfavorable treatment outcome. We observed a correlation between the cytogenetic and the MDR phenotype.
P006 Burkitt lymphoma in adults: how to treat? E. Baryakh, T. Valiev, S. Kravchenko, A. Kremenetskaya, A. Magomedova, E. Zvonkov, T. Obukhova, A. Vorobjev. The Hematology Research Centre, Russian Academy of Medical Science, Moscow, Russia Burkitt lymphoma (BL) is the most aggressive B-cell lymphoid neoplasm, with specific chromosomal abnormalities (ChA)t(8;14)(q24;q32),t(2;8)(p12;q32), t(8;22)(q24;q11). Approximately 80% of adult patients with BL have stage III-IV, that is an unfavorable prognostic factor and require an intensive chemotherapy(ChT). Aim: To evaluate an efficacy of modern ChT protocols for adult patients with BL. Patients and methods: 46 patients with BL were eligible for inclusion in our study (they had specific for BL ChA). All the patients (35 males and 11 females, mean age 24 years) participated in the study performed in Russian Hematological Research Center between 1995 and 2006. The stage (by S. B. Murphy) I,II,III,IV and B-acute lymphoblastic leukemia (B-ALL)(L3) was diagnosed in 3,4,17,7, and 14 patients respectively. According to ChT program all patients were subdivided into 3 groups: patients of group I-were treated with ÑÍÎÐ regimen; II-NHL-BFM-90 protocol; and III-a new high-intensive LB-Ì-04 program. Patients with primary diagnosis of Diffuse Large B-cell lymphoma were in group I, treated with ÑÍÎÐ regimens in other clinics. A number of patients in group I was 14, stage I was in 1 patient, II-in 3 patients, III-in 3, IV-in 4, B-ALL-in 3. 12 patients were in group II. Stage I,II,III,IV and B-ALL were diagnosed in 1, 1, 4, 1 and 5 patients, respectively. 20 patients were in group III. Stage I, II, III, IV and B-ALL were diagnosed in 1,1,10,2 and 6 patients,respectively. For patients with BL we used a new protocol LB-M-04 from August 2003. The main aim of a new treatment regimen became an intensification and treatment duration reduction in patients with BL. Our new ChT protocol is based on standard NHL-BFM-90 protocol for group of high risk patients. Despite the initial tumor mass we decided to treat BL according to 4 courses. Courses A,C,A,C were used for remission achievement. Doxorubicine was added to course A, methotrexate-to course C, interval between courses was 21 day. Results: Therapy with ÑÍÎÐ regimen was ineffective in all patients. In 9 (75%) patients, who were treated with NHLBFM-90 protocol a CR was achieved, in other 3 cases disease progressed during therapy. 1 patient died of chemotherapy complications. In 3 cases early relapses were found. 6 patients are alive in a first CR (median 40 months). 3-year
P005 Prognostic significance of the different multidrug resistance proteins co-expression in acute myeloid leukemia O. Zakharov, E. Rybalkina, A. Stavrovskaya, M. Volkova, S. Klimuk, V. Lunin, N. Zhukov. Department of oncohematology, N.N. Blokhin’s Russian Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russia Aim: Conventional induction chemotherapy induces complete remission (CR) in 65-75% of adults with de novo acute myeloid leukemia (AML) only. We investigated the prognostic significance of multidrug resistance proteins (Pglycoprotein (Pgp), BCRP, MRP1 and LRP) expression on AML blast cells with respect to CR achievement. Patients and methods: We included in analysis 42 patients (pts) with de novo AML. Expression of multidrug resistance proteins (MDR) on bone marrow blast cells was evaluated by indirect immunofluorescence and flow cytometry before chemotherapy. Expression of MDR proteins was considered as positive if at least 25% of the blast cells were stained by anti-MDR protein antibody. All pts received standard induction therapy (cytarabine, etoposide and idarubicin or daunorubicine, "3+7+7" regiment). Results: Blast cells was defined as Pgp-positive in 68.3% of cases, BCRP+ in 48.5%, MRP1+ in 56.4%, and LRP+ in 62.9% of cases. After induction therapy 27 (64.3%) pts achieved CR and 15 pts (35.7%) were resistant. MDR proteins expression was observed more frequently in resistant group, then in a sensitive one (71.4% vs 66.6% for Pgp, 62.2% vs 46.6% for MRP1, 71.4% vs 57.14% for LRP, 54.54% vs 45.45% for BCRP, respectively), but the difference was not statistically significant. Expression of all 4 MDR proteins was evaluated in 29 pts. (10 - resistant, 19 - sensitive) Blast cells co-expressed 2-4 MDR proteins in 80% of resistant pts (all studied proteins - 30%, 3 of them - 30% and 2 proteins 20%). In a group of pts achieved CR co-expression of MDR proteins was observed less frequently - 21%. The blast cells expressed 3 proteins in 3 cases only (15.7%), expression of all 4 proteins we observed only in 1 patient (5.3%) with very short CR duration (3 months). Other pts from this group (79%) express only one of the studied proteins. According to chromosome analysis 18.2% of pts with known status of all 4 studied proteins had favorable, 50% - intermediate and 31.8% unfavorable cytogenetic. We didn’t reveal any correlation between the expression of any one MDR protein and cytogenetic prognosis, but the blast cells of all pts in cytogenetically unfavorable group, expressed more then 1 protein (3 or 4 MDR proteins expressed in 71,4% of cases). In favorable and intermediate cytogenetic groups blast cells co-expressed MDR proteins in 25% of cases only (p=0,025). Conclusion: The co-expression of MDR proteins in AML
S67
has a prognostic value with respect to CR achievement in pts receiving standard antracycline-Ara-C regimens. The detection of any single protein didn’t have prognostic significance, only co-expression of 2 and more proteins predict unfavorable treatment outcome. We observed a correlation between the cytogenetic and the MDR phenotype.
P006 Burkitt lymphoma in adults: how to treat? E. Baryakh, T. Valiev, S. Kravchenko, A. Kremenetskaya, A. Magomedova, E. Zvonkov, T. Obukhova, A. Vorobjev. The Hematology Research Centre, Russian Academy of Medical Science, Moscow, Russia Burkitt lymphoma (BL) is the most aggressive B-cell lymphoid neoplasm, with specific chromosomal abnormalities (ChA)t(8;14)(q24;q32),t(2;8)(p12;q32), t(8;22)(q24;q11). Approximately 80% of adult patients with BL have stage III-IV, that is an unfavorable prognostic factor and require an intensive chemotherapy(ChT). Aim: To evaluate an efficacy of modern ChT protocols for adult patients with BL. Patients and methods: 46 patients with BL were eligible for inclusion in our study (they had specific for BL ChA). All the patients (35 males and 11 females, mean age 24 years) participated in the study performed in Russian Hematological Research Center between 1995 and 2006. The stage (by S. B. Murphy) I,II,III,IV and B-acute lymphoblastic leukemia (B-ALL)(L3) was diagnosed in 3,4,17,7, and 14 patients respectively. According to ChT program all patients were subdivided into 3 groups: patients of group I-were treated with ÑÍÎÐ regimen; II-NHL-BFM-90 protocol; and III-a new high-intensive LB-Ì-04 program. Patients with primary diagnosis of Diffuse Large B-cell lymphoma were in group I, treated with ÑÍÎÐ regimens in other clinics. A number of patients in group I was 14, stage I was in 1 patient, II-in 3 patients, III-in 3, IV-in 4, B-ALL-in 3. 12 patients were in group II. Stage I,II,III,IV and B-ALL were diagnosed in 1, 1, 4, 1 and 5 patients, respectively. 20 patients were in group III. Stage I, II, III, IV and B-ALL were diagnosed in 1,1,10,2 and 6 patients,respectively. For patients with BL we used a new protocol LB-M-04 from August 2003. The main aim of a new treatment regimen became an intensification and treatment duration reduction in patients with BL. Our new ChT protocol is based on standard NHL-BFM-90 protocol for group of high risk patients. Despite the initial tumor mass we decided to treat BL according to 4 courses. Courses A,C,A,C were used for remission achievement. Doxorubicine was added to course A, methotrexate-to course C, interval between courses was 21 day. Results: Therapy with ÑÍÎÐ regimen was ineffective in all patients. In 9 (75%) patients, who were treated with NHLBFM-90 protocol a CR was achieved, in other 3 cases disease progressed during therapy. 1 patient died of chemotherapy complications. In 3 cases early relapses were found. 6 patients are alive in a first CR (median 40 months). 3-year