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P162 Treatment of chronic lymphocytic leukaemia in elderly patients with per os fludarabine or fludarabine plus cyclophosphamide
Posters, ISH EAD 2007, Budapest, Hungary, 29 August lymphocytic leukemia. Besides establishing the demographic characteristics of 322 CLL cases studied, CD38 and ZAP7o was investigated in 58 vs. 64% of the cases while in 57% of the CLL cases FISH analysis for +12,13q ,11q and 17p was possible. Results: (1) The frequency of FISH detected aberrations in 183 CLL patients showed up 20.6; 59.5;11.4 and 8.4% for +12, 13q , 11q and 17p respectively which seems to be in good concordance with literature data. (2) The occurence of ZAP 70 level >20% was more frequent in those CLL cases requiring early therapeutic interventions (1 2 years after the diagnosis). (3) None of the FISH markers were associated with the time elapsing between the diagnosis and the start of the therapy for CLL. (4) CLL cases with long survival (> 10 years from diagnosis) have revealed an underrepresentation of 11q . Conclusion: Prospective studies will answer to what extent these biological parameters will have a role in the risk adopted therapy for CLL. P160 Alemtuzumab-induced apoptosis in vitro in chronic lymphocytic leukemia with p53 deletion L. M´ ehes *, B. Telek, L. Rejt˝ o, A. Kiss, A. Ujfalusi, M. Udvardy. University of Debrecen, Medical and Health Science Center, 2nd Department of Medicine, Regional Genetic Laboratory, Debrecen, Hungary Introduction: Alemtuzumab, a monoclonal anti-CD52 antibody has been shown to be highly effective in B-cell chronic lymphocytic leukemia, even in fludarabine-refractory diseases. The mechanism of action is partly based on immunological (complement-mediated cell lysis and antibody-dependent cellular cytotoxicity), and also on a caspase-dependent proapoptotic pathway. Alemtuzumab promotes death of chronic lymphocytic leukemia (CLL) cells in vitro. Materials and Methods: Peripheral blood mononuclear cells from 11 chronic lymphocytic leukemia patients with deletion of p53 were treated in vitro in the absence of complement with fludarabine and alemtuzumab alone, or with the combination of fludarabine + alemtuzumab. Deletion of 17p13 locus was detected using the method of fluorescence in situ hybridization (FISH). Apoptosis was evaluated after 24 and 48 h by flow cytometry analysis. Results: The apoptosis was not induced by fludarabine administered in vitro. Using alemtuzumab and the combination of fludarabine+alemtuzumab a significant increase of apoptosis could be assessed. Conclusion: The alemtuzumab and its combination with fludarabine was applied succesfully in the treatment of our chronic lymphocytic leukemia patients with p53 dysfunction. P161 BRCA1 testing in breast cancer following Hodgkin’s disease ak1 , M. Lakos1 , Zs. Moln´ ar1 , J. Papp2 , E. V´ arady1 *, B. De´ ah2 . 1 Department of T. Schneider1 , A. Rosta1 , E. Ol´ Haematology, 2 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary The risk of radiation-induced breast cancer in women treated for Hodgkin’s disease (HD) is well known, however the importance of genetic factors in the aetiology of secondary breast cancer is not yet established. We have studied whether there is an association between the development of breast cancer after radiation treatment for HD and germline mutation in the BRCA1 breast cancer-susceptibility gene. We performed mutation analyses of the BRCA1 gene in two female patients with secondary breast cancer after HD. These patients had positive family histories of breast cancer and they received chest irradiation for HD. We used PCR-SSCP methods for screening the BRCA1 mutation in the two HD patients and in their family members. We identified germline BRCA1 mutation in the first HD patient. She was irradiated at the age of 19 and the latency to breast cancer was only 5 years the
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mean time to breast cancer following radiation is approximately 15 years in the literature. The second HD patient had not mutation in the BRCA1 tumour suppressor gene but one of her family member suffering with non-Hodgkin’s lymphoma carried germline BRCA1 mutation. This study suggest that several factors contributing to second cancer risk include the carcinogenic effect of ionizing radiation in combination with possible host susceptibility. Radiation treatment of HD and mutation in the BRCA1 gene together is associated with a higher risk of breast cancer. BRCA1 mutation testing at the diagnosis of HD for female patients with familial aggregation of breast cancer is useful to identify the high risk group. Future consideration for treatment and guidelines for follow-up of these patients may reduce the occurrence of secondary breast cancer. P162 Treatment of chronic lymphocytic leukaemia in elderly patients with per os fludarabine or fludarabine plus cyclophosphamide Gy. Varga *, Z. Borb´ enyi, K. Piukovics. 2nd Dept. Int. Med. University Szeged, Hungary Introduction: Fludarabine and its combinations are the most active chemotherapeutic agents in chronic lymphocytic leukaemia (CLL). Fludarabine plus cyclophosphamide can now be considered the gold standard for initial treatment of CLL, also for elderly patients. However, in elderly patients coexisting co-morbidities could render the therapy more difficult and the aim of treatment is clinical remission, good quality of life rather than a “real” complete remission with eradication of disease. We examined the efficacy of small number of fludarabine or fludarabine plus cyclophosphamide cycles in elderly patients with CLL. Patients: During the last 4 years 42 elderly patients were treated with per os fludarabine plus cyclophosphamide (19) or with per os fludarabine (23) in our department because of progressive CLL. 30% of the patients were over 60 years fo age and 40% of patients were older than 70 years. Fludarabine (F) alone was given for 5 days (40 mg/m2 /day), combination (FC) of fludarabine (40 mg/m2 /day) and cyclophosphamide (200 mg/day) for 3 days. The average number of cycles was 3. Results: 21 patients achieved CR (NCI criteria without bone marrow) and 15 patients PR. The number of CR-s were higher in the FC group. Four patient were non-responders. Toxicity was acceptable, but three severe infections appeared, two of them caused death. In the case of relapse the same treatment proved to be effective again except 2 patients. Conclusion: In elderly patients with CLL 3 4 cycles of fludarabine or fludarabine plus cyclophosphamide could be sufficient for achievement of durable remission with good quality of life. P163 Sequential and comparative Zap-70 and CD38 analysis in chronic lymphoid leukemia patients Zs. Hevessy1 *, E. Karaszi2 , A. Frendl1 , F. Kiss1 , G. Pfliegler3 , J. Kappelmayer1 . 1 University of Debrecen, Medical and Health Science Center, Department of Clinical Biochemistry and Molecular Pathology; 3 Department of Medicine, Debrecen; 2 National Medical Center, Department of Molecular Cell Biology, Budapest, Hungary Introduction: Expression of surface antigen CD38 and the protein tyrosine kinase Zap-70 has been proposed as surrogate markers for VH mutational status and thus prognosis in chronic lymphocytic leukemia (CLL). However, there are no consensus recommendations for sample type, test timing and analysis method. Methods: We performed 216 assays from 130 B-CLL patients using indirect staining technique with anti-Zap-70 antibody (Upstate, clone 2F3.2) and goat antimouse (FITC). T/NK cells were used as an internal control for Zap-70 expression. Vertical
2 September 2007
S137
mean time to breast cancer following radiation is approximately 15 years in the literature. The second HD patient had not mutation in the BRCA1 tumour suppressor gene but one of her family member suffering with non-Hodgkin’s lymphoma carried germline BRCA1 mutation. This study suggest that several factors contributing to second cancer risk include the carcinogenic effect of ionizing radiation in combination with possible host susceptibility. Radiation treatment of HD and mutation in the BRCA1 gene together is associated with a higher risk of breast cancer. BRCA1 mutation testing at the diagnosis of HD for female patients with familial aggregation of breast cancer is useful to identify the high risk group. Future consideration for treatment and guidelines for follow-up of these patients may reduce the occurrence of secondary breast cancer. P162 Treatment of chronic lymphocytic leukaemia in elderly patients with per os fludarabine or fludarabine plus cyclophosphamide Gy. Varga *, Z. Borb´ enyi, K. Piukovics. 2nd Dept. Int. Med. University Szeged, Hungary Introduction: Fludarabine and its combinations are the most active chemotherapeutic agents in chronic lymphocytic leukaemia (CLL). Fludarabine plus cyclophosphamide can now be considered the gold standard for initial treatment of CLL, also for elderly patients. However, in elderly patients coexisting co-morbidities could render the therapy more difficult and the aim of treatment is clinical remission, good quality of life rather than a “real” complete remission with eradication of disease. We examined the efficacy of small number of fludarabine or fludarabine plus cyclophosphamide cycles in elderly patients with CLL. Patients: During the last 4 years 42 elderly patients were treated with per os fludarabine plus cyclophosphamide (19) or with per os fludarabine (23) in our department because of progressive CLL. 30% of the patients were over 60 years fo age and 40% of patients were older than 70 years. Fludarabine (F) alone was given for 5 days (40 mg/m2 /day), combination (FC) of fludarabine (40 mg/m2 /day) and cyclophosphamide (200 mg/day) for 3 days. The average number of cycles was 3. Results: 21 patients achieved CR (NCI criteria without bone marrow) and 15 patients PR. The number of CR-s were higher in the FC group. Four patient were non-responders. Toxicity was acceptable, but three severe infections appeared, two of them caused death. In the case of relapse the same treatment proved to be effective again except 2 patients. Conclusion: In elderly patients with CLL 3 4 cycles of fludarabine or fludarabine plus cyclophosphamide could be sufficient for achievement of durable remission with good quality of life. P163 Sequential and comparative Zap-70 and CD38 analysis in chronic lymphoid leukemia patients Zs. Hevessy1 *, E. Karaszi2 , A. Frendl1 , F. Kiss1 , G. Pfliegler3 , J. Kappelmayer1 . 1 University of Debrecen, Medical and Health Science Center, Department of Clinical Biochemistry and Molecular Pathology; 3 Department of Medicine, Debrecen; 2 National Medical Center, Department of Molecular Cell Biology, Budapest, Hungary Introduction: Expression of surface antigen CD38 and the protein tyrosine kinase Zap-70 has been proposed as surrogate markers for VH mutational status and thus prognosis in chronic lymphocytic leukemia (CLL). However, there are no consensus recommendations for sample type, test timing and analysis method. Methods: We performed 216 assays from 130 B-CLL patients using indirect staining technique with anti-Zap-70 antibody (Upstate, clone 2F3.2) and goat antimouse (FITC). T/NK cells were used as an internal control for Zap-70 expression. Vertical