The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Robert P Hasserjian - One of the best experts on this subject based on the ideXlab platform.
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Clinicopathologic analysis of acute myeloid Leukemia arising from chronic Myelomonocytic Leukemia
Modern Pathology, 2013Co-Authors: Elizabeth L Courville, Yue Wu, Jihen Kourda, Christine G Roth, Jillian Brockmann, Alona Muzikansky, Amir T Fathi, Laurence De Leval, Attilio Orazi, Robert P HasserjianAbstract:Acute myeloid Leukemia arising from chronic Myelomonocytic Leukemia is currently classified as acute myeloid Leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic Myelomonocytic Leukemia who progressed to acute myeloid Leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid Leukemia and 34 patients with acute myeloid Leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic Myelomonocytic Leukemia to acute myeloid Leukemia by comparing the progressed chronic Myelomonocytic Leukemia cases with a cohort of chronic Myelomonocytic Leukemia cases that did not transform to acute myeloid Leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic Myelomonocytic Leukemia to acute myeloid Leukemia. Patients with acute myeloid Leukemia ex chronic Myelomonocytic Leukemia were older ( P
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clinicopathologic analysis of acute myeloid Leukemia arising from chronic Myelomonocytic Leukemia
Modern Pathology, 2013Co-Authors: Elizabeth L Courville, Jihen Kourda, Christine G Roth, Jillian Brockmann, Alona Muzikansky, Amir T Fathi, Laurence De Leval, Attilio Orazi, Robert P HasserjianAbstract:Acute myeloid Leukemia arising from chronic Myelomonocytic Leukemia is currently classified as acute myeloid Leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic Myelomonocytic Leukemia who progressed to acute myeloid Leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid Leukemia and 34 patients with acute myeloid Leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic Myelomonocytic Leukemia to acute myeloid Leukemia by comparing the progressed chronic Myelomonocytic Leukemia cases with a cohort of chronic Myelomonocytic Leukemia cases that did not transform to acute myeloid Leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic Myelomonocytic Leukemia to acute myeloid Leukemia. Patients with acute myeloid Leukemia ex chronic Myelomonocytic Leukemia were older (P<0.01) and less likely to receive aggressive treatment (P=0.02) than de novo acute myeloid Leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid Leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid Leukemia (17 months, P=0.002) but similar to post myelodysplastic syndrome acute myeloid Leukemia. On multivariate analysis of all acute myeloid Leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid Leukemia following chronic Myelomonocytic Leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid Leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid Leukemia cases.
Charlotte M. Niemeyer - One of the best experts on this subject based on the ideXlab platform.
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Long-term serial xenotransplantation of juvenile Myelomonocytic Leukemia recapitulates human disease in Rag2-/-γc-/- mice.
Haematologica, 2016Co-Authors: Christopher Felix Krombholz, Charlotte M. Niemeyer, Konrad Aumann, Matthias Kollek, D Bertele, Silvia Fluhr, Mirjam Kunze, Christian Flotho, Miriam ErlacherAbstract:Juvenile Myelomonocytic Leukemia is a clonal malignant disease affecting young children. Current cure rates, even with allogeneic hematopoietic stem cell transplantation, are no better than 50%-60%. Pre-clinical research on juvenile Myelomonocytic Leukemia is urgently needed for the identification of novel therapies but is hampered by the unavailability of culture systems. Here we report a xenotransplantation model that allows long-term in vivo propagation of primary juvenile Myelomonocytic Leukemia cells. Persistent engraftment of leukemic cells was achieved by intrahepatic injection of 1×10(6) cells into newborn Rag2(-/-)γc(-/-) mice or intravenous injection of 5×10(6) cells into 5-week old mice. Key characteristics of juvenile Myelomonocytic Leukemia were reproduced, including cachexia and clonal expansion of Myelomonocytic progenitor cells that infiltrated bone marrow, spleen, liver and, notably, lung. Xenografted Leukemia cells led to reduced survival of recipient mice. The stem cell character of juvenile Myelomonocytic Leukemia was confirmed by successful serial transplantation that resulted in Leukemia cell propagation for more than one year. Independence of exogenous cytokines, low donor cell number and slowly progressing Leukemia are advantages of the model, which will serve as an important tool to research the pathophysiology of juvenile Myelomonocytic Leukemia and test novel pharmaceutical strategies such as DNA methyltransferase inhibition.
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criteria for evaluating response and outcome in clinical trials for children with juvenile Myelomonocytic Leukemia
Haematologica, 2015Co-Authors: Charlotte M. Niemeyer, Ulrich Germing, Seiji Kojima, Mignon L Loh, Annamaria Cseh, Todd Cooper, Christopher C Dvorak, Rebecca J Chan, Blanca Xicoy, Atsushi ManabeAbstract:Juvenile Myelomonocytic Leukemia is a rare myeloproliferative disease in young children. While hematopoietic stem cell transplantation remains the only curative therapeutic option for most patients, children with juvenile Myelomonocytic Leukemia increasingly receive novel agents in phase I-II clinical trials as pre-transplant therapy or therapy for relapse after transplantation. However, response criteria or definitions of outcome for standardized evaluation of treatment effect in patients with juvenile Myelomonocytic Leukemia are currently lacking. Here we propose criteria to evaluate the response to the non-transplant therapy and definitions of remission status after hematopoietic stem cell transplantation. For the evaluation of non-transplant therapy, we defined 6 clinical variables (white blood cell count, platelet count, hematopoietic precursors and blasts in peripheral blood, bone marrow blast percentage, spleen size and extramedullary disease) and 3 genetic variables (cytogenetic, molecular and chimerism response) which serve to describe the heterogeneous picture of response to therapy in each individual case. It is hoped that these criteria will facilitate the comparison of results between clinical trials in juvenile Myelomonocytic Leukemia.
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Juvenile Myelomonocytic Leukemia.
Current oncology reports, 2003Co-Authors: Charlotte M. Niemeyer, Christian P. KratzAbstract:Juvenile Myelomonocytic Leukemia is an aggressive neoplasia of early childhood. Only allogeneic stem cell transplantation (SCT) offers long-term cure. In the absence of an HLA-matched family donor, early SCT from an unrelated donor is the treatment of choice for most children. With clear evidence of a graft-versus-Leukemia effect and a high post-transplant relapse rate, the outcome of SCT depends, in part, on the management of immunosuppression during the procedure. The impact of pretransplant cytoreductive treatment, such as intensive chemotherapy, splenectomy, or 13-cis retinoic acid, is unclear. Hypersensitivity for granulocyte-macrophage colony-stimulating factor and pathologic activation of the Ras/MAPK pathway play an important role in the pathophysiology of juvenile Myelomonocytic Leukemia and provide the opportunity for several novel therapeutic approaches.
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Juvenile Myelomonocytic Leukemia.
Current treatment options in oncology, 2003Co-Authors: Charlotte M. Niemeyer, Christian P. KratzAbstract:Juvenile Myelomonocytic Leukemia is an aggressive neoplasia of early childhood. Only allogeneic stem cell transplantation (SCT) offers a long-term cure. In the absence of an HLA-matched family donor, early SCT from an unrelated donor will be the treatment of choice for most children. With clear evidence of a graft-versus-Leukemia effect and a high post-transplant relapse rate, outcome of SCT will depend, in part, on the management of immunosuppression during the procedure. The impact of pretransplant cytoreductive treatment, such as intensive chemotherapy, splenectomy, or 13-cis retinoic acid, is unclear. Hypersensitivity for granulocyte-macrophage colony-stimulating factor and pathologic activation of the Ras/MAPK pathway play an important role in the pathophysiology of juvenile Myelomonocytic Leukemia and will provide the opportunity for several novel therapy approaches.
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Is Juvenile Myelomonocytic Leukemia (Jmml) A Myelodysplastic or A Myeloproliferative Disease
Pediatric Research, 1999Co-Authors: Charlotte M. NiemeyerAbstract:Is Juvenile Myelomonocytic Leukemia (Jmml) A Myelodysplastic or A Myeloproliferative Disease?
Heesun J Rogers - One of the best experts on this subject based on the ideXlab platform.
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Oligomonocytic chronic Myelomonocytic Leukemia (chronic Myelomonocytic Leukemia without absolute monocytosis) displays a similar clinicopathologic and mutational profile to classical chronic Myelomonocytic Leukemia
Modern Pathology, 2017Co-Authors: Julia T Geyer, Wayne Tam, Yen-chun Liu, Zhengming Chen, Sa A Wang, Carlos Bueso-ramos, Jean Oak, Daniel A Arber, Eric Hsi, Heesun J RogersAbstract:Chronic Myelomonocytic Leukemia is characterized by persistent absolute monocytosis (≥1 × 10^9/l) in the peripheral blood and dysplasia in ≥1 lineages. In the absence of dysplasia, an acquired clonal genetic abnormality is required or causes for reactive monocytosis have to be excluded. Oligomonocytic chronic Myelomonocytic Leukemia showing increased monocytes but no absolute monocytosis in the peripheral blood occurs occasionally. These cases are likely classified as myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm, unclassifiable. A subset eventually develop overt chronic Myelomonocytic Leukemia. Better characterization of oligomonocytic chronic Myelomonocytic Leukemia is essential since the distinction between chronic Myelomonocytic Leukemia and myelodysplastic syndrome is clinically relevant. We identified 44 cases of oligomonocytic chronic Myelomonocytic Leukemia (≥10% peripheral blood monocytes with absolute monocyte count of 0.5–1 × 10^9/l) and 28 consecutive chronic Myelomonocytic Leukemia controls. Clinicopathologic features were compared and mutation analysis was performed. Oligomonocytic chronic Myelomonocytic Leukemia patients were significantly younger (median age of 65 vs 72). They had lower WBC and absolute neutrophil count, while the monocyte percentage, hemoglobin and platelet counts were similar in the two groups. The myeloid to erythroid ratio was predominantly decreased or normal, compared with the characteristic increase in chronic Myelomonocytic Leukemia ( P =0.006). 38% of patients progressed to overt chronic Myelomonocytic Leukemia (median: 12 months). The overall percentage of mutations was significantly lower in oligomonocytic chronic Myelomonocytic Leukemia. However, the most frequent mutations in both groups were the ‘signature’ chronic Myelomonocytic Leukemia mutations in ASXL1 , TET2 and SRSF2 . Mutations in CBL were found exclusively in overt chronic Myelomonocytic Leukemia. In conclusion, we demonstrate clinical and genetic similarities between overt chronic Myelomonocytic Leukemia and oligomonocytic chronic Myelomonocytic Leukemia. The findings suggest that at least a subset of oligomonocytic chronic Myelomonocytic Leukemia represents early phase ‘dysplastic type’ chronic Myelomonocytic Leukemia.
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Oligomonocytic chronic Myelomonocytic Leukemia (chronic Myelomonocytic Leukemia without absolute monocytosis) displays a similar clinicopathologic and mutational profile to classical chronic Myelomonocytic Leukemia
Modern pathology : an official journal of the United States and Canadian Academy of Pathology Inc, 2017Co-Authors: Julia T Geyer, Wayne Tam, Yen-chun Liu, Zhengming Chen, Carlos Bueso-ramos, Jean Oak, Daniel A Arber, Eric Hsi, A. Wang, Heesun J RogersAbstract:Oligomonocytic chronic Myelomonocytic Leukemia (chronic Myelomonocytic Leukemia without absolute monocytosis) displays a similar clinicopathologic and mutational profile to classical chronic Myelomonocytic Leukemia
Juan C Cigudosa - One of the best experts on this subject based on the ideXlab platform.
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cytogenetic risk stratification in chronic Myelomonocytic Leukemia
Haematologica, 2011Co-Authors: Esperanza Such, Jose Cervera, Dolors Costa, Francesc Sole, Teresa Vallespi, Elisa Luno, Rosa Collado, Maria Jose Calasanz, Jesus M Hernandezrivas, Juan C CigudosaAbstract:Background The prognostic value of cytogenetic findings in chronic Myelomonocytic Leukemia is unclear. Our purpose was to evaluate the independent prognostic impact of cytogenetic abnormalities in a large series of patients with chronic Myelomonocytic Leukemia included in the database of the Spanish Registry of Myelodysplastic Syndromes. Design and Methods We studied 414 patients with chronic Myelomonocytic Leukemia according to WHO criteria and with a successful conventional cytogenetic analysis at diagnosis. Different patient and disease characteristics were examined by univariate and multivariate methods to establish their relationship with overall survival and evolution to acute myeloid Leukemia. Results Patients with abnormal karyotype (110 patients, 27%) had poorer overall survival ( P =0.001) and higher risk of acute myeloid Leukemia evolution ( P =0.010). Based on outcome analysis, three cytogenetic risk categories were identified: low risk (normal karyotype or loss of Y chromosome as a single anomaly), high risk (presence of trisomy 8 or abnormalities of chromosome 7, or complex karyotype), and intermediate risk (all other abnormalities). Overall survival at five years for patients in the low, intermediate, and high risk cytogenetic categories was 35%, 26%, and 4%, respectively ( P <0.001). Multivariate analysis confirmed that this new CMML-specific cytogenetic risk stratification was an independent prognostic variable for overall survival ( P =0.001). Additionally, patients belonging to the high-risk cytogenetic category also had a higher risk of acute myeloid Leukemia evolution on univariate ( P =0.001) but not multivariate analysis. Conclusions Cytogenetic findings have a strong prognostic impact in patients with chronic Myelomonocytic Leukemia.
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Cytogenetic risk stratification in chronic Myelomonocytic Leukemia
Haematologica, 2010Co-Authors: Esperanza Such, Jose Cervera, Dolors Costa, Francesc Sole, Teresa Vallespi, Elisa Luno, Rosa Collado, Maria Jose Calasanz, Jesús M. Hernández-rivas, Juan C CigudosaAbstract:Background The prognostic value of cytogenetic findings in chronic Myelomonocytic Leukemia is unclear. Our purpose was to evaluate the independent prognostic impact of cytogenetic abnormalities in a large series of patients with chronic Myelomonocytic Leukemia included in the database of the Spanish Registry of Myelodysplastic Syndromes. Design and Methods We studied 414 patients with chronic Myelomonocytic Leukemia according to WHO criteria and with a successful conventional cytogenetic analysis at diagnosis. Different patient and disease characteristics were examined by univariate and multivariate methods to establish their relationship with overall survival and evolution to acute myeloid Leukemia. Results Patients with abnormal karyotype (110 patients, 27%) had poorer overall survival ( P =0.001) and higher risk of acute myeloid Leukemia evolution ( P =0.010). Based on outcome analysis, three cytogenetic risk categories were identified: low risk (normal karyotype or loss of Y chromosome as a single anomaly), high risk (presence of trisomy 8 or abnormalities of chromosome 7, or complex karyotype), and intermediate risk (all other abnormalities). Overall survival at five years for patients in the low, intermediate, and high risk cytogenetic categories was 35%, 26%, and 4%, respectively ( P
Daniel A Arber - One of the best experts on this subject based on the ideXlab platform.
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Update on the pathologic diagnosis of chronic Myelomonocytic Leukemia
Modern Pathology, 2019Co-Authors: Daniel A Arber, Attilio OraziAbstract:The diagnostic criteria for chronic Myelomonocytic Leukemia were recently revised in the 2016 World Health Organization classification update and include new and revised subtypes. In addition, molecular genetic studies have provided new insights into the prognosis and diagnosis of this myeloid neoplasm. This review summarizes the 2016 changes to the diagnostic criteria, discusses potential future changes that may impact diagnosis and provides an overview of recent advances in the diagnosis and prognosis determination of chronic Myelomonocytic Leukemia.
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Oligomonocytic chronic Myelomonocytic Leukemia (chronic Myelomonocytic Leukemia without absolute monocytosis) displays a similar clinicopathologic and mutational profile to classical chronic Myelomonocytic Leukemia
Modern Pathology, 2017Co-Authors: Julia T Geyer, Wayne Tam, Yen-chun Liu, Zhengming Chen, Sa A Wang, Carlos Bueso-ramos, Jean Oak, Daniel A Arber, Eric Hsi, Heesun J RogersAbstract:Chronic Myelomonocytic Leukemia is characterized by persistent absolute monocytosis (≥1 × 10^9/l) in the peripheral blood and dysplasia in ≥1 lineages. In the absence of dysplasia, an acquired clonal genetic abnormality is required or causes for reactive monocytosis have to be excluded. Oligomonocytic chronic Myelomonocytic Leukemia showing increased monocytes but no absolute monocytosis in the peripheral blood occurs occasionally. These cases are likely classified as myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm, unclassifiable. A subset eventually develop overt chronic Myelomonocytic Leukemia. Better characterization of oligomonocytic chronic Myelomonocytic Leukemia is essential since the distinction between chronic Myelomonocytic Leukemia and myelodysplastic syndrome is clinically relevant. We identified 44 cases of oligomonocytic chronic Myelomonocytic Leukemia (≥10% peripheral blood monocytes with absolute monocyte count of 0.5–1 × 10^9/l) and 28 consecutive chronic Myelomonocytic Leukemia controls. Clinicopathologic features were compared and mutation analysis was performed. Oligomonocytic chronic Myelomonocytic Leukemia patients were significantly younger (median age of 65 vs 72). They had lower WBC and absolute neutrophil count, while the monocyte percentage, hemoglobin and platelet counts were similar in the two groups. The myeloid to erythroid ratio was predominantly decreased or normal, compared with the characteristic increase in chronic Myelomonocytic Leukemia ( P =0.006). 38% of patients progressed to overt chronic Myelomonocytic Leukemia (median: 12 months). The overall percentage of mutations was significantly lower in oligomonocytic chronic Myelomonocytic Leukemia. However, the most frequent mutations in both groups were the ‘signature’ chronic Myelomonocytic Leukemia mutations in ASXL1 , TET2 and SRSF2 . Mutations in CBL were found exclusively in overt chronic Myelomonocytic Leukemia. In conclusion, we demonstrate clinical and genetic similarities between overt chronic Myelomonocytic Leukemia and oligomonocytic chronic Myelomonocytic Leukemia. The findings suggest that at least a subset of oligomonocytic chronic Myelomonocytic Leukemia represents early phase ‘dysplastic type’ chronic Myelomonocytic Leukemia.
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Oligomonocytic chronic Myelomonocytic Leukemia (chronic Myelomonocytic Leukemia without absolute monocytosis) displays a similar clinicopathologic and mutational profile to classical chronic Myelomonocytic Leukemia
Modern pathology : an official journal of the United States and Canadian Academy of Pathology Inc, 2017Co-Authors: Julia T Geyer, Wayne Tam, Yen-chun Liu, Zhengming Chen, Carlos Bueso-ramos, Jean Oak, Daniel A Arber, Eric Hsi, A. Wang, Heesun J RogersAbstract:Oligomonocytic chronic Myelomonocytic Leukemia (chronic Myelomonocytic Leukemia without absolute monocytosis) displays a similar clinicopathologic and mutational profile to classical chronic Myelomonocytic Leukemia
