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Martin S. Tallman

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https://www.readbyqxmd.com/read/28694182/allogeneic-hematopoietic-stem-cell-transplantation-with-myeloablative-conditioning-is-associated-with-favorable-outcomes-in-mixed-phenotype-acute-leukemia
#1
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, pre-transplant therapy and transplant outcomes for 36 well characterized pediatric and adult patients with MPAL defined according to the 2016 WHO leukemia update. A predominance of ALL-associated mutations and cytogenetic abnormalities was noted. Remission rates after induction appeared comparable among adults (20/23) and children (11/13) and among those who received ALL (10/11) or AML-type (21/25) induction...
July 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28687581/acute-myeloid-leukemia-version-3-2017-nccn-clinical-practice-guidelines-in-oncology
#2
Margaret R O'Donnell, Martin S Tallman, Camille N Abboud, Jessica K Altman, Frederick R Appelbaum, Daniel A Arber, Vijaya Bhatt, Dale Bixby, William Blum, Steven E Coutre, Marcos De Lima, Amir T Fathi, Melanie Fiorella, James M Foran, Steven D Gore, Aric C Hall, Patricia Kropf, Jeffrey Lancet, Lori J Maness, Guido Marcucci, Michael G Martin, Joseph O Moore, Rebecca Olin, Deniz Peker, Daniel A Pollyea, Keith Pratz, Farhad Ravandi, Paul J Shami, Richard M Stone, Stephen A Strickland, Eunice S Wang, Matthew Wieduwilt, Kristina Gregory, Ndiya Ogba
Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. This portion of the NCCN Guidelines for AML focuses on management and provides recommendations on the workup, diagnostic evaluation, and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.
July 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28644114/midostaurin-plus-chemotherapy-for-acute-myeloid-leukemia-with-a-flt3-mutation
#3
Richard M Stone, Sumithra J Mandrekar, Ben L Sanford, Kristina Laumann, Susan Geyer, Clara D Bloomfield, Christian Thiede, Thomas W Prior, Konstanze Döhner, Guido Marcucci, Francesco Lo-Coco, Rebecca B Klisovic, Andrew Wei, Jorge Sierra, Miguel A Sanz, Joseph M Brandwein, Theo de Witte, Dietger Niederwieser, Frederick R Appelbaum, Bruno C Medeiros, Martin S Tallman, Jürgen Krauter, Richard F Schlenk, Arnold Ganser, Hubert Serve, Gerhard Ehninger, Sergio Amadori, Richard A Larson, Hartmut Döhner
Background Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin - an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation - to standard chemotherapy would prolong overall survival in this population. Methods We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo...
June 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28597167/predictors-of-thrombohemorrhagic-early-death-in-children-and-adolescents-with-t-15-17-positive-acute-promyelocytic-leukemia-treated-with-atra-and-chemotherapy
#4
Oussama Abla, Raul C Ribeiro, Anna Maria Testi, Pau Montesinos, Ursula Creutzig, Lillian Sung, Giancarlo Di Giuseppe, Derek Stephens, James H Feusner, Bayard L Powell, Henrik Hasle, Gertjan J L Kaspers, Luciano Dalla-Pozza, Alvaro Lassaletta, Martin S Tallman, Franco Locatelli, Dirk Reinhardt, Francesco Lo-Coco, Johann Hitzler, Miguel A Sanz
Clinical trials on childhood acute promyelocytic leukemia (APL) report early death (ED) rates of 3-8%, but predictors of thrombohemorrhagic (TH)-ED are not well understood. In a retrospective study, we aimed to determine the incidence and predictors of TH-ED in childhood APL. Data were analyzed from children and adolescents with t(15;17)-positive APL (n = 683) who started treatment with all-trans retinoic acid (ATRA) and chemotherapy in different international studies. Demographic data; initial white blood cell (WBC), peripheral blood (PB) blast, and platelet counts; hemoglobin value; coagulation parameters; morphologic variant (M3 or M3v); and induction details were analyzed...
June 8, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28588020/enasidenib-in-mutant-idh2-relapsed-or-refractory-acute-myeloid-leukemia
#5
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, Stéphane 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, leading 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...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28588019/enasidenib-induces-acute-myeloid-leukemia-cell-differentiation-to-promote-clinical-response
#6
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 patients with mIDH2 in a phase 1 trial. However, its mechanism of action and biomarkers associated with response remain unclear...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28551161/independent-prognostic-significance-of-monosomy-17-and-impact-of-karyotype-complexity-in-monosomal-karyotype-complex-karyotype-acute-myeloid-leukemia-results-from-four-ecog-acrin-prospective-therapeutic-trials
#7
Stephen A Strickland, Zhuoxin Sun, Rhett P Ketterling, Athena M Cherry, Larry D Cripe, Gordon Dewald, Hugo F Fernandez, Gary A Hicks, Rodney R Higgins, Hillard M Lazarus, Mark R Litzow, Selina M Luger, Elisabeth M Paietta, Jacob M Rowe, Gail H Vance, Peter Wiernik, Anne E Wiktor, Yanming Zhang, Martin S Tallman
The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+AML is not well defined. We analyzed data from 1,592 AML patients age 17-93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28436985/functional-screen-of-msi2-interactors-identifies-an-essential-role-for-syncrip-in-myeloid-leukemia-stem-cells
#8
Ly P Vu, Camila Prieto, Elianna M Amin, Sagar Chhangawala, Andrei Krivtsov, M Nieves Calvo-Vidal, Timothy Chou, Arthur Chow, Gerard Minuesa, Sun Mi Park, Trevor S Barlowe, James Taggart, Patrick Tivnan, Raquel P Deering, Lisa P Chu, Jeong-Ah Kwon, Cem Meydan, Javier Perales-Paton, Arora Arshi, Mithat Gönen, Christopher Famulare, Minal Patel, Elisabeth Paietta, Martin S Tallman, Yuheng Lu, Jacob Glass, Francine E Garret-Bakelman, Ari Melnick, Ross Levine, Fatima Al-Shahrour, Marcus Järås, Nir Hacohen, Alexia Hwang, Ralph Garippa, Christopher J Lengner, Scott A Armstrong, Leandro Cerchietti, Glenn S Cowley, David Root, John Doench, Christina Leslie, Benjamin L Ebert, Michael G Kharas
The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis...
June 2017: Nature Genetics
https://www.readbyqxmd.com/read/28412730/the-long-noncoding-rna-trerna-decreases-dna-damage-and-is-associated-with-poor-response-to-chemotherapy-in-chronic-lymphocytic-leukemia
#9
Cecelia R Miller, Amy S Ruppert, Sydney Fobare, Timothy L Chen, Chaomei Liu, Amy Lehman, James S Blachly, Xiaoli Zhang, David M Lucas, Michael R Grever, Martin S Tallman, Ian W Flinn, Laura Z Rassenti, Thomas J Kipps, Deepa Sampath, Kevin R Coombes, Erin K Hertlein
The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28336325/allogeneic-hematopoietic-stem-cell-transplantation-is-underutilized-in-older-patients-with-myelodysplastic-syndromes
#10
Bartlomiej M Getta, Ashwin Kishtagari, Patrick Hilden, Martin S Tallman, Molly Maloy, Patrick Gonzales, Hugo Castro-Malaspina, Miguel-Angel Perales, Sergio Giralt, Roni Tamari, Virginia Klimek
Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative treatment for myelodysplastic syndrome (MDS). The proportion of MDS patients referred for transplantation evaluation, those undergoing transplantation, and the reasons for not undergoing transplantation are unknown. In this retrospective analysis, predefined HCT eligibility and indications criteria were applied to 362 unselected patients with newly diagnosed MDS seen by leukemia faculty between 2008 and 2015 at Memorial Sloan Kettering Cancer Center...
March 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28315400/multicolor-flow-cytometry-and-multigene-next-generation-sequencing-are-complementary-and-highly-predictive-for-relapse-in-acute-myeloid-leukemia-after-allogeneic-transplantation
#11
Bartlomiej M Getta, Sean M Devlin, Ross L Levine, Maria E Arcila, Abhinita S Mohanty, Ahmet Zehir, Martin S Tallman, Sergio A Giralt, Mikhail Roshal
Minimal residual disease (MRD) in acute myeloid leukemia (AML) is typically measured using multiparameter flow cytometry (MFC). Detection of leukemia mutations using multigene next-generation sequencing (NGS) can potentially be used to measure residual disease. We used a targeted 28-gene NGS panel to detect mutations and different-from-normal 10-color MFC to measure MRD in AML patients before allogeneic hematopoietic stem cell transplantation (HCT). Residual disease was defined when any abnormal blast population was detected using MFC and when any leukemia allele was detected with a variant allele frequency (VAF)  ≥ 5% using NGS...
March 15, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28293819/characteristics-features-and-factors-influencing-early-death-in-acute-promyelocytic-leukemia-experience-from-united-arab-emirates-uae
#12
Inaam Bashir Hassan, Mariam R Al Zaabi, Arif Alam, Mohammed Jawad Hashim, Martin S Tallman, Jorgen Kristensen
Although acute promyelocytic leukemia (APL) is a curable hematologic malignancy, early death (ED) remains a significant cause of treatment failure especially in developing countries. In a retrospective data analysis of 67 adult APL patients diagnosed in United Arab Emirates we report an ED rate of 11.9% which is comparable to that reported from more developed countries. We identified the following parameters at presentation as significant predictor of increased ED: Age >40 years (P = 0.015), fever (P = 0...
July 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28264800/published-abstracts-at-international-meetings-often-over-or-underestimate-the-initial-response-rate
#13
Ofrat Beyar-Katz, Jacob M Rowe, Lauren E Townsend, Martin S Tallman, Rivka Hadomi, Netanel A Horowitz
No abstract text is available yet for this article.
March 6, 2017: Blood
https://www.readbyqxmd.com/read/28174276/synergistic-antileukemic-therapies-in-notch1-induced-t-all
#14
Marta Sanchez-Martin, Alberto Ambesi-Impiombato, Yue Qin, Daniel Herranz, Mukesh Bansal, Tiziana Girardi, Elisabeth Paietta, Martin S Tallman, Jacob M Rowe, Kim De Keersmaecker, Andrea Califano, Adolfo A Ferrando
The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with NOTCH1 inhibition in T-ALL. Among these, withaferin A demonstrated the strongest cytotoxic and GSI-synergistic antileukemic effects in vitro and in vivo...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28122741/overall-survival-among-older-us-adults-with-all-remains-low-despite-modest-improvement-since-1980-seer-analysis
#15
LETTER
Mark B Geyer, Meier Hsu, Sean M Devlin, Martin S Tallman, Dan Douer, Jae H Park
No abstract text is available yet for this article.
March 30, 2017: Blood
https://www.readbyqxmd.com/read/28117898/cytogenetic-risk-determines-outcomes-after-allogeneic-transplantation-in-older-patients-with-acute-myeloid-leukemia-in-their-second-complete-remission-a-center-for-international-blood-and-marrow-transplant-research-cohort-analysis
#16
Fotios V Michelis, Vikas Gupta, Mei-Jie Zhang, Hai-Lin Wang, Mahmoud Aljurf, Ulrike Bacher, Amer Beitinjaneh, Yi-Bin Chen, Zachariah DeFilipp, Robert Peter Gale, Partow Kebriaei, Mohamed Kharfan-Dabaja, Hillard M Lazarus, Taiga Nishihori, Richard F Olsson, Betul Oran, Armin Rashidi, David A Rizzieri, Martin S Tallman, Marcos de Lima, H Jean Khoury, Brenda M Sandmaier, Daniel Weisdorf, Wael Saber
BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) offers curative potential to a number of older patients with acute myeloid leukemia (AML) in their first complete remission. However, there are limited data in the literature concerning post-HCT outcomes for older patients in their second complete remission (CR2). METHODS: The purpose of the current study was to retrospectively investigate within the Center for International Blood and Marrow Transplant Research database parameters influencing posttransplant outcomes for patients 60 years of age or older undergoing HCT for AML in CR2...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28018601/the-society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-hematologic-malignancies-multiple-myeloma-lymphoma-and-acute-leukemia
#17
Michael Boyiadzis, Michael R Bishop, Rafat Abonour, Kenneth C Anderson, Stephen M Ansell, David Avigan, Lisa Barbarotta, Austin John Barrett, Koen Van Besien, P Leif Bergsagel, Ivan Borrello, Joshua Brody, Jill Brufsky, Mitchell Cairo, Ajai Chari, Adam Cohen, Jorge Cortes, Stephen J Forman, Jonathan W Friedberg, Ephraim J Fuchs, Steven D Gore, Sundar Jagannath, Brad S Kahl, Justin Kline, James N Kochenderfer, Larry W Kwak, Ronald Levy, Marcos de Lima, Mark R Litzow, Anuj Mahindra, Jeffrey Miller, Nikhil C Munshi, Robert Z Orlowski, John M Pagel, David L Porter, Stephen J Russell, Karl Schwartz, Margaret A Shipp, David Siegel, Richard M Stone, Martin S Tallman, John M Timmerman, Frits Van Rhee, Edmund K Waller, Ann Welsh, Michael Werner, Peter H Wiernik, Madhav V Dhodapkar
Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27903528/consensus-guidelines-for-the-diagnosis-and-management-of-patients-with-classic-hairy-cell-leukemia
#18
REVIEW
Michael R Grever, Omar Abdel-Wahab, Leslie A Andritsos, Versha Banerji, Jacqueline Barrientos, James S Blachly, Timothy G Call, Daniel Catovsky, Claire Dearden, Judit Demeter, Monica Else, Francesco Forconi, Alessandro Gozzetti, Anthony D Ho, James B Johnston, Jeffrey Jones, Gunnar Juliusson, Eric Kraut, Robert J Kreitman, Loree Larratt, Francesco Lauria, Gerard Lozanski, Emili Montserrat, Sameer A Parikh, Jae H Park, Aaron Polliack, Graeme R Quest, Kanti R Rai, Farhad Ravandi, Tadeusz Robak, Alan Saven, John F Seymour, Tamar Tadmor, Martin S Tallman, Constantine Tam, Enrico Tiacci, Xavier Troussard, Clive S Zent, Thorsten Zenz, Pier Luigi Zinzani, Brunangelo Falini
Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/27895058/diagnosis-and-management-of-aml-in-adults-2017-eln-recommendations-from-an-international-expert-panel
#19
REVIEW
Hartmut Döhner, Elihu Estey, David Grimwade, Sergio Amadori, Frederick R Appelbaum, Thomas Büchner, Hervé Dombret, Benjamin L Ebert, Pierre Fenaux, Richard A Larson, Ross L Levine, Francesco Lo-Coco, Tomoki Naoe, Dietger Niederwieser, Gert J Ossenkoppele, Miguel Sanz, Jorge Sierra, Martin S Tallman, Hwei-Fang Tien, Andrew H Wei, Bob Löwenberg, Clara D Bloomfield
The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations...
January 26, 2017: Blood
https://www.readbyqxmd.com/read/27870571/high-frequency-and-poor-outcome-of-philadelphia-chromosome-like-acute-lymphoblastic-leukemia-in-adults
#20
Kathryn G Roberts, Zhaohui Gu, Debbie Payne-Turner, Kelly McCastlain, Richard C Harvey, I-Ming Chen, Deqing Pei, Ilaria Iacobucci, Marcus Valentine, Stanley B Pounds, Lei Shi, Yongjin Li, Jinghui Zhang, Cheng Cheng, Alessandro Rambaldi, Manuela Tosi, Orietta Spinelli, Jerald P Radich, Mark D Minden, Jacob M Rowe, Selina Luger, Mark R Litzow, Martin S Tallman, Peter H Wiernik, Ravi Bhatia, Ibrahim Aldoss, Jessica Kohlschmidt, Krzysztof Mrózek, Guido Marcucci, Clara D Bloomfield, Wendy Stock, Stephen Kornblau, Hagop M Kantarjian, Marina Konopleva, Elisabeth Paietta, Cheryl L Willman, Charles G Mullighan
Purpose Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. Patients and Methods The frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients...
February 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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