- Email: [email protected]
283 Hypomethylating agents improve the survival of myelodysplastic syndromes in a large population-based cohort
Posters / Leukemia Research 35 (2011) S27–S142
these complications appeared increased in patients which present dysplastic features and clonal cytogenetic abnormalities. In case of poor haematological evolution, the only treatment is bone marrow transplantation; but the correct timing for transplant is controversial. Some studies have related percentage of foetal haemoglobin and appearance of clonal abnormalities to leukemic transformation. Methods: A national centralized network has been created in Italy for the haematological follow-up of SDS patients including: morphologic review, cytogenetic analysis, molecular investigation, and clonogenic assays. The haematological controls were scheduled following the guide lines recommended during the First International Scientific Meeting on MDS (2001). Patients with an established diagnosis of SDS were recruited since 1997 to 2007. Patients’ follow-up has been up-dated at December 2010. Patients were included if they fulfilled standard diagnostic criteria for SDS. We recruited 50 patients (25 males), the median age at first observation was 7.5 years (range 0.36–21.5 years). SBDS gene mutations were detected in 42/50 patients. Four patients didn’t show mutation in the SBDS gene, but presented clinical features of SDS. In four cases analysis was not performed. Results: A mild anaemia was present in the majority of the patients, thrombocytopenia was present in 62% of the patients, 84% patients were neutropenic. More than one third of the patients presented an intermittent cytopenia. Morphological examination revealed an aplastic or hypoplastic bone marrow in 2% and 17% of the samples respectively. Megacaryocytes precursors were absent in the 26% of the smears and severely reduced in other 35% of the cases. Myelodysplastic changes were observed in 38% of the cases, being mild in 32%. Dyserytropoiesis were observed in 34% of the cases, being mild in 28%. 70% of the patients showed impaired clonogenic ability. In 20/42 cases a clonal cytogenetic evolution has been detected, while 5 cases presented clinical evolution: 2 SAA, 2 MDS and 1 LAM; 2/5 died, 3/5 are alive 6, 9 and 11 years after BMT. 4 other patients died because of infections. Details regarding morphology, clonogenic and cytogenetic features will be discussed. One third of patients are clinically stable despite clonal and dysplastic abnormalities. Conclusion: Cytopenia, dysplastic features and clonal abnormalities are frequent in SDS patients, and can be associated with a long steady clinical state. Dynamic citerias should be used in these patients to identify malignant evolution. 282 Familial myelodysplastic syndrome/acute myeloid leukemia (MDS/AML): Report of 2 families A. Stamatoullas Bastard1 , M. Loschi1 , M. Figeac2 , D. Penther3 , M.P. Callat4 , S. Lepretre1 , P. Lenain1 , N. Contentin1 , H. Tilly1 , C. Bastard3 . 1 Hematology, Centre Henri Becquerel, Rouen, 2 IRCL, Lille, 3 Genetic Laboratory, Centre Henri Becquerel, 4 Hematology Laboratory, CHU Rouen, Rouen, France Background: Familial MDS/AML is a rare diagnosis proposed when more than two first-degree relatives share a same disease. It occurs generally in the context of inherited genetic syndromes, with familial RUNX1 or CEPBA mutations, or in individuals submitted to the same environmental exposure. To date mutations of only two genes have been identified as causative mutations. Materials and Methods: We report two families with MDS/AML in 4 members of each family. Cytogenetic analysis was performed in all patients, and array CGH. In the first family, a 61 years old aunt died from AML but no details are available. PAS was 36 years old when he developed a RAEB2 with del 5(q12q32), and IPSS int-2. Despite allogeneic BMT he died from invasive aspergillosis at day 19. PAT was 44 years-old when the diagnosis of RAEB 1 was retained. Cytogenetic analysis showed a complex karyotype with 5q deletion. With a high risk IPSS, he was treated with a AML type chemotherapy but died from
S111
refractory disease. CAR, 51 years-old, was diagnosed with a RAEB2 with complex karyotype, 5q deletion and a high risk IPSS. She was treated with a AML based chemotherapy, achieved a partial remission and received an allogeneic transplant. The second family includes PAU aged 67 years, diagnosed as CMML. Cytogenetic analysis disclosed an add 12p12. She was treated with hydroxyurea, then as AML. REM, 72 years-old was diagnosed as RAEB2 with normal karyotype and int-2 IPSS. A treatment with 5 azacytidine was performed. JEA was 63 years old when a RAEB2 with 5q deletion was diagnosed, int-2 IPSS. He declined any chemotherapy and is currently in a best supportive care program. ROL aged 73 years was diagnosed as an AML (RAEBt) with normal karyotype. He achieved CR with low dose cytarabine. Discussion: We report two families with familial MDS/AML, for which no common environmental exposure was found. In the first family, we observe young age, aggressive evolution and 5q abnormalities. In the second family, patients were more aged and evolution was more indolent. Preliminary results of CGH analyses point to recurrent genomic locations in both families. 283 Hypomethylating agents improve the survival of myelodysplastic syndromes in a large population-based cohort R. Wang, X. Ma. Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA Myelodysplastic syndromes (MDS) occur primarily in older adults. Although hypomethylating agents (HMAs) have been shown to improve MDS survival in multiple randomized trials with relatively small number of patients, how HMAs perform in large, unselected, population-based cohorts is unclear. Methods: Working with the SEER-Medicare database, we identified a total of 1,604 patients (aged 66 years or older) who had MDS diagnosed as their first primary malignancy between June 1, 2004 and December 31, 2005 and assessed the impact of HMAs on their 2-year survival. Other variables of interest included age at diagnosis, sex, race (white vs. non-white), comorbidities, and median household income. Kaplan–Meier product limit was used to describe the probability of survival at various times. The log-rank test was used to compare survival curves across HMA treatment categories. Cox proportional hazard regression models were utilized to assess the impact of HMA treatment on survival. Results: 194 (12.1%) of the1604 MDS patients had received HMAs within 2 years after diagnosis. HMAs users were more likely to be younger, male, with no or only one comorbidity, and diagnosed with refractory anemia with excess blasts or refractory cytopenia with multilineage. With a median follow-up of 1.78 years, the median survival for patients treated with HMAs was longer than 2 years, compared with 1.68 years for patients not receiving HMAs (p = 0.02). In univariate analysis, HMA treatment decreased risk of death by 23% (Hazard ratio [HR] = 0.77, 95% CI: 0.62–0.95). After controlling for covariates, those treated with HMAs still had a marginally decreased risk of death (HR = 0.81, 95% CI: 0.65–1.01). Conclusion: In a large, unselected, population-based cohort of elderly MDS patients, HMAs prolonged overall survival. Further studies with longer follow-up are needed. 284 Efficacy and toxicity of azacitidine 100 mg fixed dose for the treatment and re-treatment of myelodysplastic syndrome and acute myeloid leukemia S.-P. Yeh, L.-Y. Bai, Y.-M. Liao, C.-Y. Hsieh, W.-C. Lo, C.-Y. Lin, C.-F. Chiu. Hematology and Oncology, China Medical University Hospital, Taichung, Taiwan R.O.C. Background: The efficacy and toxicity of azacitidine 100 mg fixed dose per day remain unknown and clinical trials addressing this issue are still ongoing.
these complications appeared increased in patients which present dysplastic features and clonal cytogenetic abnormalities. In case of poor haematological evolution, the only treatment is bone marrow transplantation; but the correct timing for transplant is controversial. Some studies have related percentage of foetal haemoglobin and appearance of clonal abnormalities to leukemic transformation. Methods: A national centralized network has been created in Italy for the haematological follow-up of SDS patients including: morphologic review, cytogenetic analysis, molecular investigation, and clonogenic assays. The haematological controls were scheduled following the guide lines recommended during the First International Scientific Meeting on MDS (2001). Patients with an established diagnosis of SDS were recruited since 1997 to 2007. Patients’ follow-up has been up-dated at December 2010. Patients were included if they fulfilled standard diagnostic criteria for SDS. We recruited 50 patients (25 males), the median age at first observation was 7.5 years (range 0.36–21.5 years). SBDS gene mutations were detected in 42/50 patients. Four patients didn’t show mutation in the SBDS gene, but presented clinical features of SDS. In four cases analysis was not performed. Results: A mild anaemia was present in the majority of the patients, thrombocytopenia was present in 62% of the patients, 84% patients were neutropenic. More than one third of the patients presented an intermittent cytopenia. Morphological examination revealed an aplastic or hypoplastic bone marrow in 2% and 17% of the samples respectively. Megacaryocytes precursors were absent in the 26% of the smears and severely reduced in other 35% of the cases. Myelodysplastic changes were observed in 38% of the cases, being mild in 32%. Dyserytropoiesis were observed in 34% of the cases, being mild in 28%. 70% of the patients showed impaired clonogenic ability. In 20/42 cases a clonal cytogenetic evolution has been detected, while 5 cases presented clinical evolution: 2 SAA, 2 MDS and 1 LAM; 2/5 died, 3/5 are alive 6, 9 and 11 years after BMT. 4 other patients died because of infections. Details regarding morphology, clonogenic and cytogenetic features will be discussed. One third of patients are clinically stable despite clonal and dysplastic abnormalities. Conclusion: Cytopenia, dysplastic features and clonal abnormalities are frequent in SDS patients, and can be associated with a long steady clinical state. Dynamic citerias should be used in these patients to identify malignant evolution. 282 Familial myelodysplastic syndrome/acute myeloid leukemia (MDS/AML): Report of 2 families A. Stamatoullas Bastard1 , M. Loschi1 , M. Figeac2 , D. Penther3 , M.P. Callat4 , S. Lepretre1 , P. Lenain1 , N. Contentin1 , H. Tilly1 , C. Bastard3 . 1 Hematology, Centre Henri Becquerel, Rouen, 2 IRCL, Lille, 3 Genetic Laboratory, Centre Henri Becquerel, 4 Hematology Laboratory, CHU Rouen, Rouen, France Background: Familial MDS/AML is a rare diagnosis proposed when more than two first-degree relatives share a same disease. It occurs generally in the context of inherited genetic syndromes, with familial RUNX1 or CEPBA mutations, or in individuals submitted to the same environmental exposure. To date mutations of only two genes have been identified as causative mutations. Materials and Methods: We report two families with MDS/AML in 4 members of each family. Cytogenetic analysis was performed in all patients, and array CGH. In the first family, a 61 years old aunt died from AML but no details are available. PAS was 36 years old when he developed a RAEB2 with del 5(q12q32), and IPSS int-2. Despite allogeneic BMT he died from invasive aspergillosis at day 19. PAT was 44 years-old when the diagnosis of RAEB 1 was retained. Cytogenetic analysis showed a complex karyotype with 5q deletion. With a high risk IPSS, he was treated with a AML type chemotherapy but died from
S111
refractory disease. CAR, 51 years-old, was diagnosed with a RAEB2 with complex karyotype, 5q deletion and a high risk IPSS. She was treated with a AML based chemotherapy, achieved a partial remission and received an allogeneic transplant. The second family includes PAU aged 67 years, diagnosed as CMML. Cytogenetic analysis disclosed an add 12p12. She was treated with hydroxyurea, then as AML. REM, 72 years-old was diagnosed as RAEB2 with normal karyotype and int-2 IPSS. A treatment with 5 azacytidine was performed. JEA was 63 years old when a RAEB2 with 5q deletion was diagnosed, int-2 IPSS. He declined any chemotherapy and is currently in a best supportive care program. ROL aged 73 years was diagnosed as an AML (RAEBt) with normal karyotype. He achieved CR with low dose cytarabine. Discussion: We report two families with familial MDS/AML, for which no common environmental exposure was found. In the first family, we observe young age, aggressive evolution and 5q abnormalities. In the second family, patients were more aged and evolution was more indolent. Preliminary results of CGH analyses point to recurrent genomic locations in both families. 283 Hypomethylating agents improve the survival of myelodysplastic syndromes in a large population-based cohort R. Wang, X. Ma. Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA Myelodysplastic syndromes (MDS) occur primarily in older adults. Although hypomethylating agents (HMAs) have been shown to improve MDS survival in multiple randomized trials with relatively small number of patients, how HMAs perform in large, unselected, population-based cohorts is unclear. Methods: Working with the SEER-Medicare database, we identified a total of 1,604 patients (aged 66 years or older) who had MDS diagnosed as their first primary malignancy between June 1, 2004 and December 31, 2005 and assessed the impact of HMAs on their 2-year survival. Other variables of interest included age at diagnosis, sex, race (white vs. non-white), comorbidities, and median household income. Kaplan–Meier product limit was used to describe the probability of survival at various times. The log-rank test was used to compare survival curves across HMA treatment categories. Cox proportional hazard regression models were utilized to assess the impact of HMA treatment on survival. Results: 194 (12.1%) of the1604 MDS patients had received HMAs within 2 years after diagnosis. HMAs users were more likely to be younger, male, with no or only one comorbidity, and diagnosed with refractory anemia with excess blasts or refractory cytopenia with multilineage. With a median follow-up of 1.78 years, the median survival for patients treated with HMAs was longer than 2 years, compared with 1.68 years for patients not receiving HMAs (p = 0.02). In univariate analysis, HMA treatment decreased risk of death by 23% (Hazard ratio [HR] = 0.77, 95% CI: 0.62–0.95). After controlling for covariates, those treated with HMAs still had a marginally decreased risk of death (HR = 0.81, 95% CI: 0.65–1.01). Conclusion: In a large, unselected, population-based cohort of elderly MDS patients, HMAs prolonged overall survival. Further studies with longer follow-up are needed. 284 Efficacy and toxicity of azacitidine 100 mg fixed dose for the treatment and re-treatment of myelodysplastic syndrome and acute myeloid leukemia S.-P. Yeh, L.-Y. Bai, Y.-M. Liao, C.-Y. Hsieh, W.-C. Lo, C.-Y. Lin, C.-F. Chiu. Hematology and Oncology, China Medical University Hospital, Taichung, Taiwan R.O.C. Background: The efficacy and toxicity of azacitidine 100 mg fixed dose per day remain unknown and clinical trials addressing this issue are still ongoing.