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Eytan M. Stein

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https://www.readbyqxmd.com/read/27632567/telomere-length-recovery-a-strong-predictor-of-overall-survival-in-acute-promyelocytic-leukemia
#1
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
https://www.readbyqxmd.com/read/27568819/telomere-length-and-associations-with-somatic-mutations-and-clinical-outcomes-in-acute-myeloid-leukemia
#2
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
https://www.readbyqxmd.com/read/27284485/acute-myeloid-leukemia-masquerading-as-hepatocellular-carcinoma
#3
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
https://www.readbyqxmd.com/read/27249736/evolving-therapies-in-acute-myeloid-leukemia-progress-at-last
#4
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
https://www.readbyqxmd.com/read/26660428/emerging-therapeutic-drugs-for-aml
#5
REVIEW
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
https://www.readbyqxmd.com/read/26637775/molecularly-targeted-therapies-for-acute-myeloid-leukemia
#6
REVIEW
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
https://www.readbyqxmd.com/read/26590767/idh2-inhibition-in-aml-finally-progress
#7
REVIEW
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
https://www.readbyqxmd.com/read/26553750/molecular-pathways-idh2-mutations-co-opting-cellular-metabolism-for-malignant-transformation
#8
REVIEW
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
https://www.readbyqxmd.com/read/26115047/melanoma-and-non-melanoma-skin-cancers-in-hairy-cell-leukaemia-a-surveillance-epidemiology-and-end-results-population-analysis-and-the-30-year-experience-at-memorial-sloan-kettering-cancer-center
#9
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
https://www.readbyqxmd.com/read/25823602/secondary-acute-lymphoblastic-leukaemia-is-constitutional-and-probably-not-related-to-prior-therapy
#10
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
https://www.readbyqxmd.com/read/25635757/mixed-lineage-rearranged-leukaemia-pathogenesis-and-targeting-dot1l
#11
REVIEW
Eytan M Stein, Martin S Tallman
PURPOSE OF REVIEW: The purpose of this study is to explore the recent advances in understanding the pathogenesis of leukaemias with a translocation involving the mixed lineage leukaemia (MLL) gene and therapeutic implications of these discoveries. RECENT FINDINGS: The pathogenesis of MLL-rearranged leukaemias has recently been elucidated in a flurry of clinical studies that have appeared over the past 5 years. On the basis of these studies, a phase 1 clinical trial has been initiated targeting the histone methyltransferase DOT1L with interim clinical results reported at the American Society of Hematology Annual Meeting in December 2014...
March 2015: Current Opinion in Hematology
https://www.readbyqxmd.com/read/25228556/acute-promyelocytic-leukemia-in-children-and-adolescents
#12
REVIEW
Eytan M Stein, Martin S Tallman
Acute promyelocytic leukemia (APL) is a rare subtype of AML characterized by a reciprocal balanced translocation between chromosomes 15 and 17 that fuses the PML gene with the RARα gene and leads to the leukemic phenotype. Although best described in large clinical trials of adults, APL, like other forms of AML, also occurs in children. The positive outcome of children with APL mirrors the dramatic increase in survival seen in adults since the introduction of all-trans retinoic acid (ATRA). In this paper, we review the diagnosis of APL in children as well as large, retrospective, clinical trial data collected on pediatric APL...
2014: Acta Haematologica
https://www.readbyqxmd.com/read/23768930/administration-of-atra-to-newly-diagnosed-patients-with-acute-promyelocytic-leukemia-is-delayed-contributing-to-early-hemorrhagic-death
#13
MULTICENTER STUDY
Jessica K Altman, Alfred Rademaker, Elizabeth Cull, Bing Bing Weitner, Yishai Ofran, Todd L Rosenblat, Augustin Haidau, Jae H Park, Sharona Lee Ram, James M Orsini, Sonia Sandhu, Rosalind Catchatourian, Steven M Trifilio, Nelly G Adel, Olga Frankfurt, Eytan M Stein, George Mallios, Tony Deblasio, Joseph G Jurcic, Stephen Nimer, Loann C Peterson, Hau C Kwaan, Jacob M Rowe, Dan Douer, Martin S Tallman
We hypothesized that the high early death rate (EDR) due to bleeding in acute promyelocytic leukemia (APL) is in part attributable to delays in all- trans retinoic acid (ATRA). We conducted a retrospective analysis of the timing of ATRA administration. 204 consecutive patients with newly diagnosed APL between 1992 and 2009 were identified. The EDR was 11%. 44% of early deaths occurred in the first week. Hemorrhage accounted for 61% of early deaths. ATRA was ordered the day APL was suspected in 31% of patients...
September 2013: Leukemia Research
https://www.readbyqxmd.com/read/23662989/searching-the-central-nervous-system-for-relapsed-acute-promyelocytic-leukemia
#14
COMMENT
Eytan M Stein, Martin S Tallman
No abstract text is available yet for this article.
December 2013: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/23339891/persistent-problems-with-persistent-disease-minimal-residual-disease-in-acute-myelogenous-leukemia
#15
COMMENT
Eytan M Stein, Martin S Tallman
No abstract text is available yet for this article.
February 2013: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/22888564/provocative-pearls-in-diagnosing-and-treating-acute-promyelocytic-leukemia
#16
REVIEW
Eytan M Stein, Martin S Tallman
The introduction of all-trans retinoic acid (ATRA) into routine clinical practice changed the outcome of acute promyelocytic leukemia (APL) from the most fatal to the most curable subtype of acute myeloid leukemia (AML). Patients who do not survive generally succumb within the first 30 days after presentation or diagnosis, often from intracranial or pulmonary hemorrhage caused by the characteristic coagulopathy associated with this disease. For the majority of patients who avoid hemorrhagic complications, the goals of decreasing the side effects of diagnosis and treatment-including pain, inpatient hospital days, and late sequelae of cytotoxic chemotherapy-have emerged as paramount...
July 2012: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/22791508/remission-induction-in-acute-myeloid-leukemia
#17
REVIEW
Eytan M Stein, Martin S Tallman
Inducing a complete remission (CR) in patients with acute myeloid leukemia is a prerequisite to long-term disease control with subsequent post-remission consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation. The use of 7 days of infusional cytarabine and 3 days of daunorubicin or idarubicin (7 + 3) has become the standard of care to induce CR, based on clinical trials conducted in the 1980s. Efforts to improve on the CR rate seen with the 7 + 3 regimen that translates into better overall patient survival have been disappointing...
August 2012: International Journal of Hematology
https://www.readbyqxmd.com/read/22524541/does-arsenic-trioxide-impact-fertility
#18
COMMENT
Eytan M Stein, Martin S Tallman
No abstract text is available yet for this article.
November 2012: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/22120959/hepatitis-c-and-non-hodgkin-lymphoma-the-clinical-perspective
#19
REVIEW
Sidonie K Hartridge-Lambert, Eytan M Stein, Arnold J Markowitz, Carol S Portlock
Hepatitis C virus (HCV) is a commonly transmitted infection that has both hepatic and extrahepatic repercussions. These range from the inflammatory to the oncologic with an undisputed link to hepatitis, liver cirrhosis, and hepatocellular carcinoma. Its role in the development of B cell non-Hodgkin lymphoma (B-NHL) is becoming better understood, leading to opportunities for research, therapy, and even prevention. Research in the field has progressed significantly over the last decade, with the number of patients diagnosed with HCV and B-NHL rising incrementally...
February 2012: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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