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acute leukemia in adult setting – Experience from a single Brazilian center
Poster Presentations – 12th International Symposium on Myelodysplastic Syndromes / Leukemia Research 37 S1 (2013) S1–S117
Bucharest, Romania; 2 Hematology Department, Coltea Hospital, Bucharest, Romania; 3 Hiperdia, Brasov, Romania Introduction: Myelodysplastic syndromes (MDS) are a group of heterogenous clonal stem cell disorders characterized by inefficient haematopoiesis with one or more cytopenias and increased risk of transformation to acute leukemia. Purpose: The current diagnosis includes peripheral blood morphology, bone marrow biopsy and cytogenetic exam. Clonal cytogenetic abnormalities are described in 40-60% of cases. In 1997, the established System of International Prognostic Score was based on the number of cytopenias on the peripheral blood, precentage bone marrow blasts and karyotype abnomalities. In this system are described a limited number of cytogenetic abnormalities and the importance of their forecast is underestimated. This score classify patients into four risk groups, allow overall survival and estimate the risk of progression to acute leukemia. Materials and Methods: In September 2012 the Revised International Prognostic Scoring System (R-IPSS) was developed in the framework of a project of the International Working Group for Prognosis in MDS (IWG-PM) peak. For scoring according to IPSS-R, it was taken into account: severity of cytopenias (Hb level, the number of platelets, the absolute number of neutrophils), the percentage of bone marrow blasts and cytogenetic exam. It was found that this system prognostic allows a better classification of patients with MDS into risk groups. We analyzed 25 patients diagnosed with MDS, according to the WHO classification 2001, with low risk and intermediate-1 during the period 2008-2012. These patients have been hospitalized in three centers of Hematology Departments from Romania. Results: The lot of patients was evaluated according to R-IPSS (2012) and it was found that the new system allows a better prognosis estimation and more accurate patient risk group classification. Conclusions: Although according to IPSS (1997), all patients included in this study were low risk (0-1) but applying the new scoring system has allowed a better classification of patients, six of them were with intermediate and high risk (3,5-6).
P-168 Familial myelodysplastic syndrome/acute leukemia in adult setting – Experience from a single Brazilian center M. Silva 1 , A. Leal 1 , P. Ferreira 1 , L. Nardinelly 1 , M. Silva 2 , L. Pelicario 1 , T. Lopes 1 , I. Bendit 1 , E. Velloso 1 . 1 Hematology, Hospital das Clinicas da Universidade de São Paulo, Sao Paulo, Brazil; 2 Pediatric Oncology, Grupo de Assistencia a Criança com Câncer, São José do Campos, Brazil Background: Recently more attention has been given to inherited susceptibility to MDS and acute leukemia. It is probably more common than suspected. Introduction: Familial presentations of MDS/Acute Leukemia are rare and tend to have lower age at diagnosis. They differ from the inherited bone marrow failure syndromes in the fact that they might not be preceded by it and lack classical phenotypic features. Three genetically defined familial MDS/AL are described- familial platelet disorder with propensity to myeloid malignancy (abnormality of RUNX1), familial AML with mutated CEBPA and familial MDS/AML with GATA2 mutation. Purpose: Describe two cases of familial MDS/AL diagnosed from a cohort of 570 adult patients with MDS followed at Hematology Service of HCFMUSP from 1987 to 2012. Case 1: Male, 19, two months history of anemia and suspicion of aplastic anemia. He had no previous medical history apart from left leg lymphedema. His father had a diagnosis of MDS and deceased of liver cancer at a young age. Exams showed pancytopenia, hypocellu-
S99
lar bone marrow with increase in myeloblasts and monosomy 7. No related donor was found, and after 6 cycles of azacitidine, progression to AML was detected. He died of infection after unrelated HSCT. Case 2: Two brothers were referred for investigation of familial MDS. Male, 21, with AML in first remission diagnosed at the age of 10. After 4 years without hemotherapy, low platelet count and dysplastic bone marrow were detected. The younger brother, 19, was diagnosed with T lymphoblastic lymphoma without bone marrow involvement also at the age of ten. Platelet count was low at diagnosis and after chemotherapy. Investigation revealed a dysplastic bone marrow with 15% of myeloblasts. They have three siblings. All have altered platelet aggregation, one also has low platelet count. Fanconi anemia was ruled out (normal diepoxybutane test and no phenotypical features). Paternal family history is unknown and there is no history of hematological disease on maternal side. Direct sequencing of RUNX1(exons 3-8) did not identify mutations. Results: Although we have no molecular confirmation, clinical and laboratory features suggest familial MDS with GATA2 mutation in case one and familial platelet disorder with propensity to develop myeloid malignancy in case two. Conclusions: Although molecular confirmation of underlying defect can be difficult, identification of cases of familial propensity to MDS is important and should be actively thought after, especially in younger adults. It has impact in the search of bone marrow donors and family follow up.
P-169 Presence of JAK2 V617F mutation in myeloproliferative and myelodysplastic syndrome patients F. Duarte, T. Santos, M. Barbosa, T. Santos, R. Gonçalves. Hematology/Transplant, Federal University of Ceará, Fortaleza, Brazil Background: JAK 2 mutation in myeloproliferative (MPS) and myelodisplastic syndromes (MDS). Introduction: The chronic myeloproliferative syndromes or myeloproliferative neoplasms (MPN), are clonal hematopoietic stem cell diseases, in which there is increased proliferation of myeloid series with ineffective maturation, which leads to peripheral blood leukocytosis, increased erythrocyte mass or thrombocytosis. Several progress to fibrosis or leukemic transformation. A mutation in the pseudokinase domain JH2 gene Janus kinase 2 (JAK2 V617F) was described in myeloproliferative diseases. This mutation is associated to increased risk of tromboembolic events in some of these MPN Purpose: What does it mean JAK 2 mutation in MDS? Incidence and impact in treatment. Materials and Methods: We present three cases of patients with MPS/MDS with JAK-2 positive. Results: The first one is a 80 years old with ’refractory anemia with ring sideroblasts and thrombocytosis’ RARS-T and JAK-2 positive and radiotherapy treatment in 2007. Myelogram: dyseritropoesis, dysmegakaryopoesis >10%; assynchronism of maturation and binucleation; presence of micromegakariocytes, megakaryocytes hipolobulated and 81% ringed sideroblasts. A bone marrow biopsy: hypercellular marrow with architectural disorder, characterized by megaloblastides erythroblasts and megakaryocytes arranged in peripheral position. Reticulin: fibrosis grade I. Karyotype revealed 46,XYand Hb 78,7g/L; leukocytes 7.740/mm3 and platelets 949/mm3 . The second case is a 69 years old male patient, with MPS/MDS. The bone marrow: predominance of megakaryocyte and granulocyte without evidence of myelofibrosis. Peripheral blood count: anemia (Hb:109 g/L) and leukocytosis (Lc: 16.500/mm3 ).The last patient is a 66 years old male with MDP/MDS andV617F JAK 2 positive. He present anemia and leucocytosis (Hb = 109 g/L and leucocytes = 16500/m3 ). In mielogram is observed mild dyseritropoiesis and iron deposit absence.
Bucharest, Romania; 2 Hematology Department, Coltea Hospital, Bucharest, Romania; 3 Hiperdia, Brasov, Romania Introduction: Myelodysplastic syndromes (MDS) are a group of heterogenous clonal stem cell disorders characterized by inefficient haematopoiesis with one or more cytopenias and increased risk of transformation to acute leukemia. Purpose: The current diagnosis includes peripheral blood morphology, bone marrow biopsy and cytogenetic exam. Clonal cytogenetic abnormalities are described in 40-60% of cases. In 1997, the established System of International Prognostic Score was based on the number of cytopenias on the peripheral blood, precentage bone marrow blasts and karyotype abnomalities. In this system are described a limited number of cytogenetic abnormalities and the importance of their forecast is underestimated. This score classify patients into four risk groups, allow overall survival and estimate the risk of progression to acute leukemia. Materials and Methods: In September 2012 the Revised International Prognostic Scoring System (R-IPSS) was developed in the framework of a project of the International Working Group for Prognosis in MDS (IWG-PM) peak. For scoring according to IPSS-R, it was taken into account: severity of cytopenias (Hb level, the number of platelets, the absolute number of neutrophils), the percentage of bone marrow blasts and cytogenetic exam. It was found that this system prognostic allows a better classification of patients with MDS into risk groups. We analyzed 25 patients diagnosed with MDS, according to the WHO classification 2001, with low risk and intermediate-1 during the period 2008-2012. These patients have been hospitalized in three centers of Hematology Departments from Romania. Results: The lot of patients was evaluated according to R-IPSS (2012) and it was found that the new system allows a better prognosis estimation and more accurate patient risk group classification. Conclusions: Although according to IPSS (1997), all patients included in this study were low risk (0-1) but applying the new scoring system has allowed a better classification of patients, six of them were with intermediate and high risk (3,5-6).
P-168 Familial myelodysplastic syndrome/acute leukemia in adult setting – Experience from a single Brazilian center M. Silva 1 , A. Leal 1 , P. Ferreira 1 , L. Nardinelly 1 , M. Silva 2 , L. Pelicario 1 , T. Lopes 1 , I. Bendit 1 , E. Velloso 1 . 1 Hematology, Hospital das Clinicas da Universidade de São Paulo, Sao Paulo, Brazil; 2 Pediatric Oncology, Grupo de Assistencia a Criança com Câncer, São José do Campos, Brazil Background: Recently more attention has been given to inherited susceptibility to MDS and acute leukemia. It is probably more common than suspected. Introduction: Familial presentations of MDS/Acute Leukemia are rare and tend to have lower age at diagnosis. They differ from the inherited bone marrow failure syndromes in the fact that they might not be preceded by it and lack classical phenotypic features. Three genetically defined familial MDS/AL are described- familial platelet disorder with propensity to myeloid malignancy (abnormality of RUNX1), familial AML with mutated CEBPA and familial MDS/AML with GATA2 mutation. Purpose: Describe two cases of familial MDS/AL diagnosed from a cohort of 570 adult patients with MDS followed at Hematology Service of HCFMUSP from 1987 to 2012. Case 1: Male, 19, two months history of anemia and suspicion of aplastic anemia. He had no previous medical history apart from left leg lymphedema. His father had a diagnosis of MDS and deceased of liver cancer at a young age. Exams showed pancytopenia, hypocellu-
S99
lar bone marrow with increase in myeloblasts and monosomy 7. No related donor was found, and after 6 cycles of azacitidine, progression to AML was detected. He died of infection after unrelated HSCT. Case 2: Two brothers were referred for investigation of familial MDS. Male, 21, with AML in first remission diagnosed at the age of 10. After 4 years without hemotherapy, low platelet count and dysplastic bone marrow were detected. The younger brother, 19, was diagnosed with T lymphoblastic lymphoma without bone marrow involvement also at the age of ten. Platelet count was low at diagnosis and after chemotherapy. Investigation revealed a dysplastic bone marrow with 15% of myeloblasts. They have three siblings. All have altered platelet aggregation, one also has low platelet count. Fanconi anemia was ruled out (normal diepoxybutane test and no phenotypical features). Paternal family history is unknown and there is no history of hematological disease on maternal side. Direct sequencing of RUNX1(exons 3-8) did not identify mutations. Results: Although we have no molecular confirmation, clinical and laboratory features suggest familial MDS with GATA2 mutation in case one and familial platelet disorder with propensity to develop myeloid malignancy in case two. Conclusions: Although molecular confirmation of underlying defect can be difficult, identification of cases of familial propensity to MDS is important and should be actively thought after, especially in younger adults. It has impact in the search of bone marrow donors and family follow up.
P-169 Presence of JAK2 V617F mutation in myeloproliferative and myelodysplastic syndrome patients F. Duarte, T. Santos, M. Barbosa, T. Santos, R. Gonçalves. Hematology/Transplant, Federal University of Ceará, Fortaleza, Brazil Background: JAK 2 mutation in myeloproliferative (MPS) and myelodisplastic syndromes (MDS). Introduction: The chronic myeloproliferative syndromes or myeloproliferative neoplasms (MPN), are clonal hematopoietic stem cell diseases, in which there is increased proliferation of myeloid series with ineffective maturation, which leads to peripheral blood leukocytosis, increased erythrocyte mass or thrombocytosis. Several progress to fibrosis or leukemic transformation. A mutation in the pseudokinase domain JH2 gene Janus kinase 2 (JAK2 V617F) was described in myeloproliferative diseases. This mutation is associated to increased risk of tromboembolic events in some of these MPN Purpose: What does it mean JAK 2 mutation in MDS? Incidence and impact in treatment. Materials and Methods: We present three cases of patients with MPS/MDS with JAK-2 positive. Results: The first one is a 80 years old with ’refractory anemia with ring sideroblasts and thrombocytosis’ RARS-T and JAK-2 positive and radiotherapy treatment in 2007. Myelogram: dyseritropoesis, dysmegakaryopoesis >10%; assynchronism of maturation and binucleation; presence of micromegakariocytes, megakaryocytes hipolobulated and 81% ringed sideroblasts. A bone marrow biopsy: hypercellular marrow with architectural disorder, characterized by megaloblastides erythroblasts and megakaryocytes arranged in peripheral position. Reticulin: fibrosis grade I. Karyotype revealed 46,XYand Hb 78,7g/L; leukocytes 7.740/mm3 and platelets 949/mm3 . The second case is a 69 years old male patient, with MPS/MDS. The bone marrow: predominance of megakaryocyte and granulocyte without evidence of myelofibrosis. Peripheral blood count: anemia (Hb:109 g/L) and leukocytosis (Lc: 16.500/mm3 ).The last patient is a 66 years old male with MDP/MDS andV617F JAK 2 positive. He present anemia and leucocytosis (Hb = 109 g/L and leucocytes = 16500/m3 ). In mielogram is observed mild dyseritropoiesis and iron deposit absence.