The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Jorge E. Cortes - One of the best experts on this subject based on the ideXlab platform.
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Chronic Myeloid Leukemia: reminiscences and dreams
Haematologica, 2016Co-Authors: Tariq I. Mughal, Jorge E. Cortes, M W Deininger, Jerald P. Radich, Jane F. Apperley, Timothy P. Hughes, Christine J. Harrison, Carlo Gambacorti-passerini, Giuseppe Saglio, George Q. DaleyAbstract:With the deaths of Janet Rowley and John Goldman in December 2013, the world lost two pioneers in the field of chronic Myeloid Leukemia. In 1973, Janet Rowley, unraveled the cytogenetic anatomy of the Philadelphia chromosome, which subsequently led to the identification of the BCR-ABL1 fusion gene and its principal pathogenetic role in the development of chronic Myeloid Leukemia. This work was also of major importance to support the idea that cytogenetic changes were drivers of leukemogenesis. John Goldman originally made seminal contributions to the use of autologous and allogeneic stem cell transplantation from the late 1970s onwards. Then, in collaboration with Brian Druker, he led efforts to develop ABL1 tyrosine kinase inhibitors for the treatment of patients with chronic Myeloid Leukemia in the late 1990s. He also led the global efforts to develop and harmonize methodology for molecular monitoring, and was an indefatigable organizer of international conferences. These conferences brought together clinicians and scientists, and accelerated the adoption of new therapies. The abundance of praise, tributes and testimonies expressed by many serve to illustrate the indelible impressions these two passionate and affable scholars made on so many people’s lives. This tribute provides an outline of the remarkable story of chronic Myeloid Leukemia, and in writing it, it is clear that the historical triumph of biomedical science over this Leukemia cannot be considered without appreciating the work of both Janet Rowley and John Goldman.
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Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia
Expert review of hematology, 2016Co-Authors: Yasmin Rosshandler, Ann Q. Shen, Jorge E. Cortes, Hanna Jean KhouryAbstract:Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic Myeloid Leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic Myeloid Leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic Myeloid Leukemia.
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Hypocellular acute Myeloid Leukemia in adults: analysis of the clinical outcome of 123 patients
Haematologica, 2011Co-Authors: Aref Al-kali, Sergej Konoplev, Stefan Faderl, Jorge E. Cortes, Erpei Lin, Tapan M. Kadia, Farhad Ravandi, Mohamad Ayoubi, Mark Brandt, Hagop M. KantarjianAbstract:Background The hypocellular variant of acute Myeloid Leukemia accounts for less than 10% of all cases of adult acute Myeloid Leukemia. It is defined by having less than 20 percent of cellular bone marrow in a biopsy at presentation. It is unclear in the literature whether the outcome of hypocellular acute Myeloid Leukemia differs from that of non-hypocellular acute Myeloid Leukemia. Design and Methods We retrospectively analyzed all the cases reported to be hypocellular acute Myeloid Leukemia between 2000 and 2009. A second pathology review was conducted and the diagnosis was confirmed in all cases. Results One hundred twenty-three (9%) patients were identified: patients with hypocellular acute Myeloid Leukemia were older than those with non-hypocellular acute Myeloid Leukemia ( P =0.009) and more frequently presented with cytopenias ( P
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Novel therapies for patients with chronic Myeloid Leukemia.
Expert review of anticancer therapy, 2004Co-Authors: Francis J. Giles, Hagop M. Kantarjian, Jorge E. CortesAbstract:The most immediate issues that will have a major impact on the long-term survival of patients with chronic Myeloid Leukemia is the optimal use of imatinib mesylate (Gleevec, Novartis) and the development of effective therapies for those patients who are intolerant of, or become resistant to, optimal doses of this agent. Of the multiple new agents that are currently being developed for patients with chronic Myeloid Leukemia, most are being investigated in patients who have developed resistance to imatinib, which is a confounding factor in itself. The mechanisms of action of novel agents are diverse and they may have a variably synergistic therapeutic relationship with imatinib. The complete blockade of the intracellular pathways that are triggered by Bcr-Abl, combined with successful reversal of apoptotic and/or angiogenic abnormalities in chronic Myeloid Leukemia, may well lead to a cure for the majority of patients.
Robert P Hasserjian - One of the best experts on this subject based on the ideXlab platform.
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Reproducibility and prognostic significance of morphologic dysplasia in de novo acute Myeloid Leukemia.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology Inc, 2015Co-Authors: Olga K. Weinberg, Olga Pozdnyakova, Federico Campigotto, Daniel J. Deangelo, Richard Stone, Donna Neuberg, Robert P HasserjianAbstract:The 2008 WHO classification of acute Myeloid Leukemia includes a category of acute Myeloid Leukemia with myelodysplasia-related changes; however, the significance of multilineage dysplasia alone is controversial and its reproducibility has not been evaluated in acute Myeloid Leukemia. We performed an in-depth analysis of morphologic dysplasia in 159 de novo acute Myeloid Leukemia cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008 WHO criteria, there were 89 acute Myeloid Leukemia—not otherwise specified (56%) and 43 acute Myeloid Leukemia with myelodysplasia-related changes (27%), while 27 cases were ambiguous as to myelodysplasia-related changes status due to limited maturing cells (acute Myeloid Leukemia—not evaluable, 17%). On multivariable analysis, neither acute Myeloid Leukemia with myelodysplasia-related changes nor acute Myeloid Leukemia—not evaluable showed significantly different event-free survival compared with acute Myeloid Leukemia—not otherwise specified in the 137 patients treated with induction chemotherapy. When individual dysplastic features were analyzed, only micromegakaryocytes and hypogranulated Myeloid cells emerged as factors significantly associated with shorter event-free survival in a multivariable analysis that included the other significant covariates of age, white blood count, platelet count, abnormal karyotype and stem-cell transplantation. Our findings indicate that the current 2008 WHO definition of multilineage dysplasia in acute Myeloid Leukemia in its current form is not optimal, and that the use of a more restricted definition of morphologic dysplasia results in more relevant risk stratification that is independent of other conventional prognostic factors.
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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.
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Acute Myeloid Leukemia: advances in diagnosis and classification.
International journal of laboratory hematology, 2013Co-Authors: Robert P HasserjianAbstract:Summary Acute Myeloid Leukemia is an aggressive Myeloid neoplasm characterized by ≥20% myeloblasts in the blood or bone marrow. Current treatment strategies for acute Myeloid Leukemia are based on both patient-related parameters such as age and performance status as well as the intrinsic characteristics of particular disease subtypes. Subtyping of acute Myeloid Leukemia requires an integration of information from the patient's clinical history (such as any prior preleukemic Myeloid neoplasm or cytotoxic potentially leukemogenic therapy), the Leukemia morphology, cytogenetic findings, and the mutation status of particular genes (NPM1, FLT3, and CEBPA). In recent years, a barrage of information has become available regarding gene mutations that occur in acute Myeloid Leukemia and their influence on prognosis. Future therapies for acute Myeloid Leukemia will increasingly rely on the genetic signatures of individual Leukemias and will adjust therapy to the predicted disease aggressiveness as well as employ therapies targeted against particular deregulated genetic pathways. This article reviews current standards for diagnosing and classifying acute Myeloid Leukemia according to the 2008 WHO Classification. Data that have subsequently accumulated regarding newly characterized gene mutations are also presented. It is anticipated that future Leukemia classifications will employ a combination of karyotypic features and the gene mutation pattern to stratify patients to increasingly tailored treatment plans.
Hanna Jean Khoury - One of the best experts on this subject based on the ideXlab platform.
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Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia
Expert review of hematology, 2016Co-Authors: Yasmin Rosshandler, Ann Q. Shen, Jorge E. Cortes, Hanna Jean KhouryAbstract:Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic Myeloid Leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic Myeloid Leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic Myeloid Leukemia.
Yaoyu Chen - One of the best experts on this subject based on the ideXlab platform.
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Omacetaxine mepesuccinate in the treatment of intractable chronic Myeloid Leukemia.
OncoTargets and therapy, 2014Co-Authors: Yaoyu ChenAbstract:In a significant proportion of patients with chronic Myeloid Leukemia, resistance to BCR-ABL tyrosine kinase inhibitors develops due to acquisition of BCR-ABL kinase domain mutations and insensitivity of Leukemia stem cells to tyrosine kinase inhibitors. Omacetaxine mepesuccinate (formerly called homoharringtonine) is a natural alkaloid that inhibits protein synthesis and induces cell death. Omacetaxine mepesuccinate has been recently approved by the US Food and Drug Administration to treat patients with chronic Myeloid Leukemia who failed to respond to multiple tyrosine kinase inhibitors and/or acquired the BCR-ABL-T315I mutation. In this review, we discuss the use and effectiveness of omacetaxine mepesuccinate in the treatment of chronic Myeloid Leukemia, with coverage of its pharmacology, mode of action, and pharmacokinetics. We believe that omacetaxine mepesuccinate will be beneficial to many patients with chronic Myeloid Leukemia who do not respond well to tyrosine kinase inhibitors.
Armand Keating - One of the best experts on this subject based on the ideXlab platform.
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Advances in targeted therapy for chronic Myeloid Leukemia.
Expert review of anticancer therapy, 2003Co-Authors: Karen W.l. Yee, Armand KeatingAbstract:Despite the lack of long-term survival data, the impressive results obtained with imatinib mesylate (Gleevec®) therapy and the lack of serious adverse events have significantly altered the management of patients with chronic Myeloid Leukemia. Nevertheless, a large proportion of patients with more advanced disease will develop resistance to imatinib mesylate monotherapy. To prevent the development of resistance, an understanding of the pathophysiology of chronic Myeloid Leukemia, including the signaling pathways that are activated by the BCR–ABL fusion protein, and the mechanisms of resistance to imatinib are required. This review summarizes the pathogenesis of chronic Myeloid Leukemia and the potential therapeutic impact of small molecule inhibitors that target pathways critical to the growth or survival of the leukemic cells in patients with chronic Myeloid Leukemia.
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t cell blast crisis in chronic Myeloid Leukemia
Leukemia & Lymphoma, 1991Co-Authors: Keith A Stewart, Andre C Schuh, Armand KeatingAbstract:Involvement of T cells in chronic Myeloid Leukemia is a rare event. Twenty-one cases of T-cell lymphoid blast crisis of chronic Myeloid Leukemia reported in the literature are reviewed, and evidence for T-lineage involvement is evaluated.Patients present with a distinctive clinical phenotype. Most frequently they are young males with extensive extramedullary deposits of blast cells, rapidly progressive lymphadenopathy, organomegaly and pleural involvement. Clonal cytogenetic evolution is common and survival short. The identification of this phenotype may be of clinical and prognostic significance.
