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Eytan M. Stein

Zachary D Epstein-Peterson, Sean M Devlin, Eytan M Stein, Elihu Estey, Martin S Tallman
PURPOSE: Measurable residual disease (MRD) has prognostic importance for patients with acute myeloid leukemia (AML). How leukemia providers incorporate MRD into routine practice remains undefined. PATIENTS AND METHODS: A survey was developed and distributed to a large sample of leukemia physicians. Demographic information was collected along with details concerning MRD practices. A multivariable logistic regression model evaluated provider characteristics predictive of MRD utilization...
February 13, 2018: Leukemia Research
Amir T Fathi, Courtney D DiNardo, Irina Kline, Laurie Kenvin, Ira Gupta, Eyal C Attar, Eytan M Stein, Stephane de Botton
Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity...
January 18, 2018: JAMA Oncology
Eytan M Stein, Gaetano Bonifacio, Dominick Latremouille-Viau, Annie Guerin, Sherry Shi, Patrick Gagnon-Sanschagrin, Owanate Briggs, George J Joseph
OBJECTIVE: To describe the setting, duration, and costs of induction and consolidation chemotherapy for adults with newly-diagnosed acute myeloid leukemia (AML), who are candidates for standard induction chemotherapy, in the US. METHODS: Adults newly-diagnosed with AML who received standard induction chemotherapy in an inpatient setting were identified from the Truven Health Analytics MarketScan (2006-2015) and SEER-Medicare (2007-2011) databases. Patients were observed from induction therapy start to the first of hematopoietic stem cell transplant, 180 days after induction discharge, health plan enrollment/data availability end, or death...
January 22, 2018: Journal of Medical Economics
Eytan M Stein
Mutations in IDH2 genes (mIDH2) occur in approximately 12% of patients with acute myeloid leukemia. Enasidenib is an oral, small-molecule inhibitor of mIDH2 proteins. Enasidenib is shown to suppress the oncometabolite, 2-hydroxyglutarate, and promote differentiation of leukemic bone marrow blasts. In a Phase I dose-escalation and expansion study, 40.3% of patients with relapsed/refractory acute myeloid leukemia responded to enasidenib monotherapy, including 19.3% who achieved complete remission and 11% who proceeded to transplant...
January 2018: Future Oncology
Eytan M Stein, Roland B Walter, Harry P Erba, Amir T Fathi, Anjali S Advani, Jeffrey E Lancet, Farhad Ravandi, Tibor Kovacsovics, Daniel J DeAngelo, Dale Bixby, Stefan Faderl, Anand P Jillella, Phoenix A Ho, Megan M O'Meara, Baiteng Zhao, Charles Biddle-Snead, Anthony S Stein
Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33, which is expressed in the majority of acute myeloid leukemia (AML) patients. This phase 1 study evaluated the safety, pharmacokinetics, and preliminary activity of vadastuximab talirine and determined the recommended monotherapy dose in patients with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab talirine in specific subpopulations of relapsed AML, and in a cohort of older, treatment-naive patients...
January 25, 2018: Blood
Eytan M Stein
No abstract text is available yet for this article.
August 2017: Journal of Oncology Practice
Bartlomiej M Getta, Mikhail Roshal, Junting Zheng, Jae H Park, Eytan M Stein, Ross Levine, Esperanza B Papadopoulos, Ann A Jakubowski, Nancy A Kernan, Peter Steinherz, Richard J O'Reilly, Miguel-Angel Perales, Sergio A Giralt, Martin S Tallman, Brian C Shaffer
Mixed phenotype acute leukemia (MPAL) represents a poorly characterized group of acute leukemias that lack an accepted therapeutic approach and are typically associated with poor outcomes. We present our experience of genomic profiling, pretransplantation therapy, and transplantation outcomes for 36 well-characterized pediatric and adult patients with MPAL, defined according to the 2016 World Health Organization leukemia update. A predominance of acute lymphoid leukemia (ALL)-associated mutations and cytogenetic abnormalities was noted...
November 2017: Biology of Blood and Marrow Transplantation
Eytan M Stein, Courtney D DiNardo, Daniel A Pollyea, Amir T Fathi, Gail J Roboz, Jessica K Altman, Richard M Stone, Daniel J DeAngelo, Ross L Levine, Ian W Flinn, Hagop M Kantarjian, Robert Collins, Manish R Patel, Arthur E Frankel, Anthony Stein, Mikkael A Sekeres, Ronan T Swords, Bruno C Medeiros, Christophe Willekens, Paresh Vyas, Alessandra Tosolini, Qiang Xu, Robert D Knight, Katharine E Yen, Sam Agresta, Stephane de Botton, Martin S Tallman
Recurrent mutations in isocitrate dehydrogenase 2 ( IDH2 ) occur in ∼12% of patients with acute myeloid leukemia (AML). Mutated IDH2 proteins neomorphically synthesize 2-hydroxyglutarate resulting in DNA and histone hypermethylation, which leads to blocked cellular differentiation. Enasidenib (AG-221/CC-90007) is a first-in-class, oral, selective inhibitor of mutant-IDH2 enzymes. This first-in-human phase 1/2 study assessed the maximum tolerated dose (MTD), pharmacokinetic and pharmacodynamic profiles, safety, and clinical activity of enasidenib in patients with mutant- IDH2 advanced myeloid malignancies...
August 10, 2017: Blood
Michael D Amatangelo, Lynn Quek, Alan Shih, Eytan M Stein, Mikhail Roshal, Muriel D David, Benoit Marteyn, Noushin Rahnamay Farnoud, Stephane de Botton, Olivier A Bernard, Bin Wu, Katharine E Yen, Martin S Tallman, Elli Papaemmanuil, Virginie Penard-Lacronique, Anjan Thakurta, Paresh Vyas, Ross L Levine
Recurrent mutations at R140 and R172 in isocitrate dehydrogenase 2 ( IDH2 ) occur in many cancers, including ∼12% of acute myeloid leukemia (AML). In preclinical models these mutations cause accumulation of the oncogenic metabolite R -2-hydroxyglutarate (2-HG) and induce hematopoietic differentiation block. Single-agent enasidenib (AG-221/CC-90007), a selective mutant IDH2 (mIDH2) inhibitor, produced an overall response rate of 40.3% in relapsed/refractory AML (rrAML) patients with m IDH2 in a phase 1 trial...
August 10, 2017: Blood
Attila Feher, Polydoros N Kampaktsis, Rekha Parameswaran, Eytan M Stein, Richard Steingart, Dipti Gupta
BACKGROUND: Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). MATERIALS AND METHODS: Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count <50,000 cells per µL within 7 days of AMI...
February 2017: Oncologist
Muhamed Baljevic, Bogdan Dumitriu, Ju-Whei Lee, Elisabeth M Paietta, Peter H Wiernik, Janis Racevskis, Christina Chen, Eytan M Stein, Robert E Gallagher, Jacob M Rowe, Frederick R Appelbaum, Bayard L Powell, Richard A Larson, Steven E Coutré, Jeffrey Lancet, Mark R Litzow, Selina M Luger, Neal S Young, Martin S Tallman
Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established...
2016: Acta Haematologica
Justin M Watts, Bogdan Dumitriu, Patrick Hilden, Ashwin Kishtagari, Franck Rapaport, Christina Chen, Jihae Ahn, Sean M Devlin, Eytan M Stein, Raajit Rampal, Ross L Levine, Neal Young, Martin S Tallman
We examined the genetic implications and clinical impact of telomere length (TL) in 67 patients with acute myeloid leukemia (AML). There was a trend toward improved survival at 6 months in patients with longer TL. We found that patients with activating mutations, such as FLT3-ITD, had shorter TL, while those with mutations in epigenetic modifying enzymes, particularly IDH1 and IDH2, had longer TL. These are intriguing findings that warrant further investigation in larger cohorts. Our data show the potential of TL as a predictive biomarker in AML and identify genetic subsets that may be particularly vulnerable to telomere-targeted therapies...
October 2016: Leukemia Research
Ghaith F Abu-Zeinah, Paul Weisman, Karuna Ganesh, Seth S Katz, Ahmet Dogan, Ghassan K Abou-Alfa, Eytan M Stein, William Jarnagin, Michael J Mauro, James J Harding
Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation...
June 2016: Journal of Gastrointestinal Oncology
Daniel J DeAngelo, Eytan M Stein, Farhad Ravandi
Acute myeloid leukemia (AML) is an acquired disease characterized by chromosomal translocations and somatic mutations that lead to leukemogenesis. Systemic combination chemotherapy with an anthracycline and cytarabine remains the standard induction regimen for "fit" adults. Patients who achieve complete remission generally receive postinduction therapy with cytarabine-based chemotherapy or an allogeneic bone marrow transplant. Those unfit for induction chemotherapy are treated with hypomethylating agents (HMAs), low-dose cytarabine, or they are offered supportive care alone with transfusions and prophylactic antimicrobials...
2016: American Society of Clinical Oncology Educational Book
Eytan M Stein, Martin S Tallman
Multiple new drugs are being developed to treat acute myeloid leukemia (AML), including novel formulations of traditional chemotherapy-antibody drug conjugates and agents that target specific mutant enzymes. Next-generation sequencing has allowed us to discover the genetic mutations that lead to the development and clinical progression of AML. Studies of clonal hierarchy suggest which mutations occur early and dominate. This has led to targeted therapy against mutant driver proteins as well as the development of drugs such as CPX-351 and SGN-CD33A whose mechanisms of action and efficacy may not be dependent on mutational complexity...
January 7, 2016: Blood
Eytan M Stein
The past 15 years have seen major leaps in our understanding of the molecular genetic mutations that act as drivers of acute myeloid leukemia (AML). Clinical trials of agents against specific mutant proteins, such as FLT3-internal tandem duplications (ITDs) and isocitrate dehydrogenase mutations (IDHs) are ongoing. This review discusses agents in clinical trials that target specific gene mutations and/or epigenetic targets.
2015: Hematology—the Education Program of the American Society of Hematology
Eytan M Stein
Isocitrate dehydrogenase (IDH) catalyzes the conversion of isocitrate to alpha ketoglutarate. IDH occurs in three isoforms, IDH1, located in the cytoplasm, IDH2 located in the mitochondria, and IDH3, which functions as part of the TCA cycle. Mutations in the active site of IDH1 at position R132 and an analogous mutation in the IDH2 gene at position R172 have been discovered. Notably, many cases of acute myeloid leukemia (AML) have mutations in R172 and R140. The impact of these mutations and early results of inhibiting mutant IDH2 with the reversible inhibitor AG-221 are discussed in this review...
June 2015: Best Practice & Research. Clinical Haematology
Eytan M Stein
Mutations in mitochondrial IDH2, one of the three isoforms of IDH, were discovered in patients with gliomas in 2009 and subsequently described in acute myelogenous leukemia (AML), angioimmunoblastic T-cell lymphoma, chondrosarcoma, and intrahepatic chloangiocarcinoma. The effects of mutations in IDH2 on cellular metabolism, the epigenetic state of mutated cells, and cellular differentiation have been elucidated in vitro and in vivo. Mutations in IDH2 lead to an enzymatic gain of function that catalyzes the conversion of alpha-ketoglutarate to beta-hydroxyglutarate (2-HG)...
January 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Justin M Watts, Ashwin Kishtagari, Meier Hsu, Mario E Lacouture, Michael A Postow, Jae H Park, Eytan M Stein, Julie Teruya-Feldstein, Omar Abdel-Wahab, Sean M Devlin, Martin S Tallman
Few studies have examined melanoma and non-melanoma skin cancer (NMSC) incidence rates after a diagnosis of hairy cell leukaemia (HCL). We assessed 267 HCL patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) and Surveillance, Epidemiology and End Results (SEER) data for melanoma and NMSC incidence rates after HCL. Incidence data from MSKCC patients demonstrated a 10-year combined melanoma and NMSC skin cancer rate of 11·3%, melanoma 4·4% and NMSC 6·9%. Molecular analysis of skin cancers from MSKCC patients revealed activating RAS mutations in 3/9 patients, including one patient with melanoma...
October 2015: British Journal of Haematology
Chezi Ganzel, Sean Devlin, Dan Douer, Jacob M Rowe, Eytan M Stein, Martin S Tallman
Very little is known about secondary acute lymphoblastic leukaemia (s-ALL). This retrospective analysis studied a cohort of s-ALL patients treated at a single centre between 1994 and 2013, while comparing therapy-associated ALL (t-ALL) and antecedent malignancy ALL (am-ALL) patients. Thirty-two patients with s-ALL were identified. The overall incidence was 9.4% among ALL adults while T-cell s-ALL was rare (12% of s-ALLs). The median time interval between two malignant diagnoses was 5.3 years (range: 0.1-28)...
July 2015: British Journal of Haematology
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