The Experts below are selected from a list of 27843 Experts worldwide ranked by ideXlab platform
Henrik Hasle - One of the best experts on this subject based on the ideXlab platform.
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bone marrow immunophenotyping by flow cytometry in refractory Cytopenia of childhood
Haematologica, 2015Co-Authors: Anna M Aalbers, Marry M Van Den Heuveleibrink, Irith Baumann, Michael Dworzak, Henrik Hasle, Franco Locatelli, Barbara De Moerloose, Markus Schmugge, Ester Mejstrikova, Michaela NovakovaAbstract:Refractory Cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory Cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory Cytopenia from the immune-mediated bone marrow failure syndrome (very) severe aplastic anemia can be challenging. Flow cytometric immunophenotyping of bone marrow has been shown to be a valuable diagnostic tool in differentiating myelodysplastic syndrome from non-clonal Cytopenias in adults. Here, we performed the first comprehensive flow cytometric analysis of immature myeloid, lymphoid cells and erythroid cells, and granulocytes, monocytes, and lymphoid cells in bone marrow obtained from a large prospective cohort of 81 children with refractory Cytopenia. Children with refractory cyotopenia had a strongly reduced myeloid compartment, but not as severe as children with aplastic anemia. Furthermore, the number of flow cytometric abnormalities was significantly higher in children with refractory Cytopenia than in healthy controls and in children with aplastic anemia, but lower than in advanced myelodysplastic syndrome. We conclude that flow cytometric immunophenotyping could be a relevant addition to histopathology in the diagnosis of refractory Cytopenia of childhood. (The multi-center studies EWOG-MDS RC06 and EWOG-MDS 2006 are registered at clinicaltrials.gov identifiers 00499070 and 00662090, respectively).
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the clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory Cytopenia of childhood a prospective study by ewog mds
Leukemia, 2014Co-Authors: Anna M Aalbers, Michael Dworzak, V H J Van Der Velden, Ayami Yoshimi, Alexandra Fischer, Peter Noellke, C M Zwaan, I Baumann, H B Beverloo, Henrik HasleAbstract:The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory Cytopenia of childhood: a prospective study by EWOG-MDS
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applicability of a reproducible flow cytometry scoring system in the diagnosis of refractory Cytopenia of childhood
Leukemia, 2013Co-Authors: Anna M Aalbers, Marry M Van Den Heuveleibrink, Michael Dworzak, Henrik Hasle, Franco Locatelli, V De Haas, J Te G Marvelde, A X De Jong, M E L Van Der Burg, Barbara De MoerlooseAbstract:Applicability of a reproducible flow cytometry scoring system in the diagnosis of refractory Cytopenia of childhood
Anna M Aalbers - One of the best experts on this subject based on the ideXlab platform.
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bone marrow immunophenotyping by flow cytometry in refractory Cytopenia of childhood
Haematologica, 2015Co-Authors: Anna M Aalbers, Marry M Van Den Heuveleibrink, Irith Baumann, Michael Dworzak, Henrik Hasle, Franco Locatelli, Barbara De Moerloose, Markus Schmugge, Ester Mejstrikova, Michaela NovakovaAbstract:Refractory Cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory Cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory Cytopenia from the immune-mediated bone marrow failure syndrome (very) severe aplastic anemia can be challenging. Flow cytometric immunophenotyping of bone marrow has been shown to be a valuable diagnostic tool in differentiating myelodysplastic syndrome from non-clonal Cytopenias in adults. Here, we performed the first comprehensive flow cytometric analysis of immature myeloid, lymphoid cells and erythroid cells, and granulocytes, monocytes, and lymphoid cells in bone marrow obtained from a large prospective cohort of 81 children with refractory Cytopenia. Children with refractory cyotopenia had a strongly reduced myeloid compartment, but not as severe as children with aplastic anemia. Furthermore, the number of flow cytometric abnormalities was significantly higher in children with refractory Cytopenia than in healthy controls and in children with aplastic anemia, but lower than in advanced myelodysplastic syndrome. We conclude that flow cytometric immunophenotyping could be a relevant addition to histopathology in the diagnosis of refractory Cytopenia of childhood. (The multi-center studies EWOG-MDS RC06 and EWOG-MDS 2006 are registered at clinicaltrials.gov identifiers 00499070 and 00662090, respectively).
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the clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory Cytopenia of childhood a prospective study by ewog mds
Leukemia, 2014Co-Authors: Anna M Aalbers, Michael Dworzak, V H J Van Der Velden, Ayami Yoshimi, Alexandra Fischer, Peter Noellke, C M Zwaan, I Baumann, H B Beverloo, Henrik HasleAbstract:The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory Cytopenia of childhood: a prospective study by EWOG-MDS
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applicability of a reproducible flow cytometry scoring system in the diagnosis of refractory Cytopenia of childhood
Leukemia, 2013Co-Authors: Anna M Aalbers, Marry M Van Den Heuveleibrink, Michael Dworzak, Henrik Hasle, Franco Locatelli, V De Haas, J Te G Marvelde, A X De Jong, M E L Van Der Burg, Barbara De MoerlooseAbstract:Applicability of a reproducible flow cytometry scoring system in the diagnosis of refractory Cytopenia of childhood
Sungsoo Yoon - One of the best experts on this subject based on the ideXlab platform.
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asxl1 is a molecular predictor in idiopathic Cytopenia of undetermined significance
Leukemia & Lymphoma, 2019Co-Authors: Dong Yeop Shin, Jin Kyun Park, Kyongok Im, Sang Mee Hwang, Sungsoo YoonAbstract:AbstractWe analyzed the mutational profile of idiopathic Cytopenia of undetermined significance (ICUS) compared with that of myelodysplastic syndrome (MDS). Targeted sequencing of 88 genes associat...
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hematological manifestations of human immunodeficiency virus infection and the effect of highly active anti retroviral therapy on Cytopenia
The Korean Journal of Hematology, 2011Co-Authors: Se Youn Choi, Sungsoo Yoon, Youn Ak Choi, Ji Hyun Kwon, Pyoeng Gyun Choe, Wan Beom Park, Seonyang Park, Myoungdon OhAbstract:Background The aim of this study is to investigate the hematological manifestations of human immunodeficiency virus (HIV) infection, the risk factors for Cytopenia, and the effect of highly active anti-retroviral therapy (HAART) on Cytopenia.
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association between elevated hemolysis at diagnosis and early mortality and risk of thrombosis in paroxysmal nocturnal hemoglobinuria pnh patients with Cytopenia
Blood, 2010Co-Authors: Sungsoo Yoon, Deogyeon Jo, Junho Jang, Jooseop Chung, Sang Kyun SohnAbstract:Abstract 4241 Introduction: PNH is a rare, progressive and life threatening disease driven by chronic hemolysis leading to thrombosis, renal impairment, pain, severe fatigue, poor quality of life and premature death. Thrombosis is the leading cause of death (accounting for 40–67% of PNH-related deaths) and was recently identified as a significant risk factor for mortality in Asian PNH patients. Abdominal pain is a common and distressing symptom in PNH and has also been found to be risk factor for thrombosis and mortality in PNH patients. In PNH patients with concomitant aplasia/Cytopenias (PNH-Cytopenia), the symptoms associated with hemolytic PNH (i.e., severe fatigue and anemia) may be attributed to a hypocellular marrow, potentially masking the life threatening risk of hemolysis-mediated thrombosis and abdominal pain. Here we evaluate the correlation of clinical risk factors with hemolytic symptoms in cytopenic PNH patients. Methods: We retrospectively analyzed medical charts of 286 PNH patients from the National Data Registry in South Korea to identify aplastic PNH patients with evidence of hemolytic symptoms at the time of diagnosis. We defined PNH-Cytopenia patients with evidence of at least 2 of the following hematological values at diagnosis: Hgb <10 g/dL; ANC <1.5×109/L; thromboCytopenia <100×109/L. Hemolysis was defined as LDH °A1.5 fold above the upper limit of normal (ULN). Results: The median patient age was 37 years (range: 8 to 88 years) and median PNH duration was 7.8 years. At diagnosis, median PNH granulocyte clone was 49% and LDH was 3.9-fold above ULN. Median platelet count was 99×109/L and median ANC was 1.2×109/L, 21% with ANC <1.0×109/L. PNH-Cytopenia was identified at diagnosis in 42% of PNH patients. PNH-cytopenic patients experienced a similar prevalence of hemolytic symptoms and mortality compared to PNH patients with no evidence of Cytopenia (PNH) (see table below). Thrombosis was equally prevalent in PNH-Cytopenia compared to PNH (12% vs18%; P=0.175). Abdominal pain was equally prevalent in PNH-Cytopenia and PNH (52% vs 42%; P=0.112) and there was similar mortality between the 2 groups (13% vs 11%; P=0.631). There was a significantly higher prevalence of mortality (14% vs 4%; p=0.048), thrombosis (22% vs 4%; p=0.003) and abdominal pain (53% vs 32%; p=0.007) in patients with elevated hemolysis (°A LDH 1.5 above ULN) compared to patients without hemolysis. We found that 69% of PNH-Cytopenia patients demonstrated elevated hemolysis at diagnosis. Thrombosis was identified in 17% of PNH-Cytopenia patients with elevated hemolysis compared to 3% with no evidence of elevated LDH (p=0.051); abdominal pain (59% vs 32%; p= 0.012) and death (16% vs 3%; p=0.070) were higher in PNH-Cytopenia patients with hemolysis compared to PNH-Cytopenia patients without hemolysis. CONCULSION: These data demonstrate that the presence of hemolysis at diagnosis is associated with of life-threatening thrombosis, poor quality of life, and mortality in PNH patients. Despite the evidence of hypoplasia, PNH-Cytopenia patients with hemolysis demonstrate a higher risk of life-threatening thrombosis, pain, and mortality. These data indicate that hemolysis is a potential risk factor for life- threatening complications independent of the presence of Cytopenia in patients with PNH. Treatment for PNH patients with Cytopenias should focus on both controlling hemolysis as well as improving hypoplasia. View this table: Disclosures: No relevant conflicts of interest to declare.
Jonna Komulainenebrahim - One of the best experts on this subject based on the ideXlab platform.
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gain of function samd9l mutations cause a syndrome of Cytopenia immunodeficiency mds and neurological symptoms
Blood, 2017Co-Authors: Bianca Tesi, Josef Davidsson, Matthias Voss, Elisa Rahikkala, Tim D Holmes, Samuel C C Chiang, Jonna KomulainenebrahimAbstract:Several monogenic causes of familial myelodysplastic syndrome (MDS) have recently been identified. We studied two families with Cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction. Genetic studies uncovered heterozygous missense mutations in SAMD9L, a tumor suppressor gene located on chromosome arm 7q. Consistent with a gain-of-function effect, ectopic expression of the two identified SAMD9L mutants decreased cell proliferation relative to wild-type protein. Of the ten individuals identified heterozygous for either SAMD9L mutation, three developed MDS upon loss of the mutated SAMD9L allele following intracellular infections associated with myeloid, B and NK cell deficiency. Five other individuals, three with spontaneously resolved cytopenic episodes in infancy, harbored hematopoietic revertant mosaicism by uniparental disomy of 7q with loss of the mutated allele or additional in cis SAMD9L truncating mutations. Examination of one individual indicated that somatic reversions were postnatally selected. Somatic mutations were tracked to CD34(+) hematopoietic progenitor cell populations, being further enriched in B and NK cells. Stimulation of these cell types with interferon (IFN)-α or -γ induced SAMD9L expression. Clinically, revertant mosaicism was associated with milder disease, yet neurological manifestations persisted in three individuals. Two carriers also harbored a rare, in trans germline SAMD9L missense loss-of-function variant, potentially counteracting the SAMD9L mutation. Our results demonstrate that gain-of-function mutations in the tumor suppressor SAMD9L cause Cytopenia, immunodeficiency, variable neurological presentation, and predisposition to MDS with -7/del(7q), where hematopoietic revertant mosaicism commonly ameliorated clinical manifestations. The findings suggest a role for SAMD9L in regulating IFN-driven, demand-adapted hematopoiesis. (Less)
Ayami Yoshimi - One of the best experts on this subject based on the ideXlab platform.
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comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory Cytopenia of childhood
Haematologica, 2014Co-Authors: Ayami Yoshimi, Marry M Van Den Heuveleibrink, Irith Baumann, Stephan Schwarz, Ingrid Simonitschklupp, Pascale De Paepe, Vit Campr, Gitte Kerndrup, Maureen J Osullivan, Rita DevitoAbstract:Refractory Cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory Cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory Cytopenia of childhood, the long-term risk of relapse or clonal evolution remains.
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the clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory Cytopenia of childhood a prospective study by ewog mds
Leukemia, 2014Co-Authors: Anna M Aalbers, Michael Dworzak, V H J Van Der Velden, Ayami Yoshimi, Alexandra Fischer, Peter Noellke, C M Zwaan, I Baumann, H B Beverloo, Henrik HasleAbstract:The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory Cytopenia of childhood: a prospective study by EWOG-MDS
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immunosuppressive therapy with anti thymocyte globulin and cyclosporine a in selected children with hypoplastic refractory Cytopenia
Haematologica, 2007Co-Authors: Ayami Yoshimi, Marry M Van Den Heuveleibrink, Irith Baumann, M Fuhrer, Eva Bergstrasser, U Gobel, Karlwalter Sykora, Thomas Klingebiel, Ute Grosswieltsch, Alexandra FischerAbstract:It is currently unknown whether immunosuppressive therapy or hematopoietic stem cell transplantation is the most appropriate treatment strategy for children with refractory Cytopenia and normal karyotype or trisomy 8. We report on 31 children with hypoplastic refractory Cytopenia treated with immunosuppressive therapy consisting of antithymocyte globulin and cyclosporine. At 6 months, 22 of 29 evaluable patients had a complete or partial response; a total of ten patients achieved a complete response at varying time points. Six patients subsequently received a transplant because of non-response, progression to advanced myelodysplastic syndrome or evolution of monosomy 7. Overall and failure-free survival rates at 3 years were 88% and 57%, respectively.
