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Martin S. Tallman

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https://www.readbyqxmd.com/read/29746955/micafungin-versus-posaconazole-prophylaxis-in-acute-leukemia-or-myelodysplastic-syndrome-a-randomized-study
#1
David J Epstein, Susan K Seo, Yao-Ting Huang, Jay H Park, Virginia M Klimek, Ellin Berman, Martin S Tallman, Mark G Frattini, Genovefa A Papanicolaou
OBJECTIVES: To compare the effectiveness and tolerability of micafungin versus posaconazole during chemotherapy-induced neutropenia in acute leukemia (AL) and myelodysplastic syndrome (MDS). METHODS: Patients with AL or MDS undergoing chemotherapy were randomized to open-label micafungin 100 mg intravenously daily or posaconazole suspension 400 mg orally twice daily until neutrophil recovery, up to 28 days. Patients were followed for 12 weeks. The primary endpoint was prophylaxis failure (premature discontinuation due to infection, intolerance, adverse event, or death)...
May 7, 2018: Journal of Infection
https://www.readbyqxmd.com/read/29724899/the-dot1l-inhibitor-pinometostat-reduces-h3k79-methylation-and-has-modest-clinical-activity-in-adult-acute-leukemia
#2
Eytan M Stein, Guillermo Garcia-Manero, David A Rizzieri, Raoul Tibes, Jesus G Berdeja, Michael R Savona, Mojca Jongen-Lavrenic, Jessica K Altman, Blythe Thomson, Stephen J Blakemore, Scott R Daigle, Nigel J Waters, A Benjamin Suttle, Alicia Clawson, Roy Pollock, Andrei Krivtsov, Scott A Armstrong, Jorge DiMartino, Eric Hedrick, Bob Löwenberg, Martin S Tallman
Pinometostat (EPZ-5676) is a first-in-class, small-molecule inhibitor of the histone methyltransferase DOT1L. In this phase 1 study, pinometostat was evaluated for safety and efficacy in adult patients with advanced acute leukemias, particularly those involving MLL rearrangements ( MLL-r ) resulting from 11q23 translocations. Fifty-one patients were enrolled into 6 dose escalation cohorts (n=26) and 2 expansion cohorts (n=25) at pinometostat doses of 54 and 90 mg/m2 /day by continuous intravenous infusion in 28-day cycles...
May 3, 2018: Blood
https://www.readbyqxmd.com/read/29706486/time-to-repeal-and-replace-response-criteria-for-acute-myeloid-leukemia
#3
REVIEW
Clara Derber Bloomfield, Elihu Estey, Lisa Pleyer, Andre C Schuh, Eytan M Stein, Martin S Tallman, Andrew Wei
The International Working Group (IWG) response criteria for acute myeloid leukemia, published in 2003, have remained the standard by which the efficacy of new drugs is measured in clinical trials. Over the last decade, concepts related to treatment response have been challenged by several factors; for example, the dissociation between early clinical response and survival outcome in older patients, the recognition that epigenetic and newer differentiating-agent therapies may produce delayed responses and also hematologic improvement/transfusion independence without a morphologic response, and evidence that remissions without minimal (or measurable) residual disease (MRD) may result in outcomes superior to those of morphologic remissions with persistent MRD...
March 27, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29703492/predictive-factors-of-fatal-bleeding-in-acute-promyelocytic-leukemia
#4
Simon Mantha, Martin S Tallman, Sean M Devlin, Gerald A Soff
Acute promyelocytic leukemia (APL) is associated with a profound coagulopathy. Based on retrospective assessments, several potential risk factors for hemorrhagic morbidity and mortality have emerged. Several studies have shown elevated white blood cell (WBC) count at presentation to be a robust predictor of bleeding events. Other clinical and laboratory parameters have been evaluated with variable association with hemorrhagic morbidity or mortality. These include ECOG performance status, age, morphological subtype, platelet count, peripheral blood blast count, ethnicity, body mass index, prothrombin time, activated partial thromboplastin time, lactate dehydrogenase, d-dimers, creatinine and fibrinogen levels...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29544131/similar-incidence-of-typhlitis-in-patients-receiving-various-doses-of-daunorubicin-or-idarubicin-as-induction-for-acute-myeloid-leukemia
#5
Amanda N Seddon, Joshua Chaim, Oguz Akin, Esther Drill, Angela G Michael, Nelly Adel, Martin S Tallman
BACKGROUND: The current standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) is an anthracycline plus cytarabine. Both anthracyclines and cytarabine have been associated with the development of typhlitis, a serious adverse event characterized by inflammation of the bowel wall in patients with profound neutropenia, diagnosed by abdominal CT imaging and clinical symptoms. Given the paucity of available data, the aim of our study was to determine the incidence of typhlitis among AML patients receiving induction chemotherapy with idarubicin 12 mg/m2 (IDA), daunorubicin 60 mg/m2 (DNA60), or daunorubicin 90 mg/m2 (DNA90)...
May 2018: Leukemia Research
https://www.readbyqxmd.com/read/29487070/minimal-residual-hairy-cell-leukemia-eradication-with-moxetumomab-pasudotox-phase-i-results-and-long-term-follow-up
#6
Robert J Kreitman, Martin S Tallman, Tadeusz Robak, Steven Coutre, Wyndham H Wilson, Maryalice Stetler-Stevenson, David J FitzGerald, Linda Santiago, Guozhi Gao, Mark C Lanasa, Ira Pastan
Anti-CD22 moxetumomab pasudotox achieved 46% complete remissions (CRs) in previously reported phase I testing in relapsed/refractory hairy cell leukemia (HCL; n=28). The importance of minimal residual disease (MRD) after CR in HCL is unknown. A 21-patient extension cohort received 50 µg/kg every other day for 3 doses in 4-week cycles. These patients plus 12 previously reported at this upper dose level received 143 cycles without dose-limiting toxicity. The combined 33-patient cohort achieved 64% CR and 88% overall response rates, with median CR duration of 42...
February 27, 2018: Blood
https://www.readbyqxmd.com/read/29482173/widespread-use-of-measurable-residual-disease-in-acute-myeloid-leukemia-practice
#7
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...
April 2018: Leukemia Research
https://www.readbyqxmd.com/read/29431698/mef2c-phosphorylation-is-required-for-chemotherapy-resistance-in-acute-myeloid-leukemia
#8
Fiona C Brown, Eric Still, Richard P Koche, Christina Y Yim, Sumiko Takao, Paolo Cifani, Casie Reed, Shehana Gunasekera, Scott B Ficarro, Peter Romanienko, Willie Mark, Craig McCarthy, Elisa de Stanchina, Mithat Gonen, Venkatraman Seshan, Patrick Bhola, Conor O'Donnell, Barbara Spitzer, Crystal Stutzke, Vincent-Philippe Lavallée, Josée Hébert, Andrei V Krivtsov, Ari Melnick, Elisabeth M Paietta, Martin S Tallman, Anthony Letai, Guy Sauvageau, Gayle Pouliot, Ross Levine, Jarrod A Marto, Scott A Armstrong, Alex Kentsis
In acute myeloid leukemia (AML), chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that Mef2cS222A/S222A knock-in mutant mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9 MEF2C phosphorylation was required for leukemia stem cell maintenance and induced by MARK kinases in cells...
April 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29407583/pegaspargase-related-high-grade-hepatotoxicity-in-a-pediatric-inspired-adult-acute-lymphoblastic-leukemia-regimen-does-not-predict-recurrent-hepatotoxicity-with-subsequent-doses
#9
Patrick W Burke, Ibrahim Aldoss, Matthew A Lunning, Sean M Devlin, Martin S Tallman, Vinod Pullarkat, Ann M Mohrbacher, Dan Douer
Pediatric acute lymphoblastic leukemia (ALL) regimens, including higher cumulative asparaginase doses, have been investigated in adult ALL to improve outcomes. Preliminary results are promising, but hepatotoxicity rates with long-acting pegaspargase are greater in adults than children. However, adult pegaspargase-related hepatotoxicity is not as clearly defined despite being the commonest adult toxicity. We studied the frequency and characteristics of high-grade pegaspargase-related hepatotoxicity in newly diagnosed adults on a pediatric-inspired regimen that included six planned pegaspargase doses, 2000 IU/m2 /dose intravenously, with doses given at least four weeks apart and not discontinued or dose-reduced for previous hepatotoxicity...
March 2018: Leukemia Research
https://www.readbyqxmd.com/read/29386195/phase-2-trial-of-a-multivalent-wt1-peptide-vaccine-galinpepimut-s-in-acute-myeloid-leukemia
#10
Peter G Maslak, Tao Dao, Yvette Bernal, Suzanne M Chanel, Rong Zhang, Mark Frattini, Todd Rosenblat, Joseph G Jurcic, Renier J Brentjens, Maria E Arcila, Raajit Rampal, Jae H Park, Dan Douer, Laura Katz, Nicholas Sarlis, Martin S Tallman, David A Scheinberg
A National Cancer Institute consensus study on prioritization of cancer antigens ranked the Wilms tumor 1 (WT1) protein as the top immunotherapy target in cancer. We previously reported a pilot study of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia (AML) patients. We have now conducted a phase 2 study investigating this vaccine in adults with AML in first complete remission (CR1). Patients received 6 vaccinations administered over 10 weeks with the potential to receive 6 additional monthly doses if they remained in CR1...
February 13, 2018: Blood Advances
https://www.readbyqxmd.com/read/29365325/choosing-for-whom-to-recommend-allogeneic-transplantation-for-acute-myeloid-leukemia-in-cr1-a-continued-complicated-conversation
#11
Kamal N Menghrajani, Martin S Tallman
No abstract text is available yet for this article.
January 23, 2018: Blood Advances
https://www.readbyqxmd.com/read/29316456/disease-characteristics-and-clinical-outcomes-in-patients-aged-less-than-40-with-chronic-lymphocytic-leukemia
#12
Bartlomiej M Getta, Sean Devlin, Jae H Park, Martin S Tallman, Ellin Berman
Outcomes in very young CLL patients (age ≤40) are not well characterized. We compared 71 consecutive patients aged ≤40 with 142 "older" matched patients >40 from our institution and used SEER database as an independent comparison group. Patients in the two age groups were diagnosed at similar Rai stage. At diagnosis, very young patients had a similar rate of adverse cytogenetics, IGHV mutation and ZAP70 expression and had lower beta-2-microglobulin and a lower incidence of second malignancies...
February 2018: Leukemia Research
https://www.readbyqxmd.com/read/29296827/clinical-impact-of-baalc-expression-in-high-risk-acute-promyelocytic-leukemia
#13
Antonio R Lucena-Araujo, Diego A Pereira-Martins, Luisa C Koury, Pedro L Franca-Neto, Juan L Coelho-Silva, Virginia M de Deus Wagatsuma, Raul A M Melo, Rosane Bittencourt, Katia Pagnano, Ricardo Pasquini, Carlos S Chiattone, Evandro M Fagundes, Maria de Lourdes Chauffaille, Stanley L Schrier, Martin S Tallman, Raul C Ribeiro, David Grimwade, Arnold Ganser, Bob Löwenberg, Francesco Lo-Coco, Miguel A Sanz, Nancy Berliner, Eduardo M Rego
Although overexpression of the brain and acute leukemia, cytoplasmic ( BAALC ) gene is associated with primary resistant disease and shorter relapse-free, disease-free, and overall survival in different subsets of acute myeloid leukemia (AML), little is known about its clinical impact in acute promyelocytic leukemia (APL). Using real-time reverse transcriptase polymerase chain reaction, we showed that BAALC expression is significantly lower in APL compared with other subsets of AML ( P < .001). We also demonstrated that BAALC overexpression was associated with shorter disease-free survival (DFS) (hazard ratio [HR], 4...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29283906/new-therapeutic-strategies-for-high-risk-acute-myeloid-leukemia
#14
Kamal Menghrajani, Martin S Tallman
PURPOSE OF REVIEW: Treatments for acute myeloid leukemia (AML) had remained essentially unchanged for several years; however, the advent of molecular testing has generated insight into the biology of this disease which is now being translated into clinical practice. New treatment strategies which improve drug delivery and exploit cellular targets are changing the landscape of how we treat this disease. RECENT FINDINGS: Induction therapy is in the process of changing for several patient populations...
March 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29139135/phase-1-study-of-quizartinib-in-combination-with-induction-and-consolidation-chemotherapy-in-patients-with-newly-diagnosed-acute-myeloid-leukemia
#15
Jessica K Altman, James M Foran, Keith W Pratz, Denise Trone, Jorge E Cortes, Martin S Tallman
Novel therapies have potential to improve outcomes in patients with acute myeloid leukemia (AML) harboring FLT3-ITD mutations that have high risk of relapse and poor survival following standard of care (SOC) cytarabine/anthracycline-based induction/consolidation chemotherapy. Quizartinib is a selective and highly potent FLT3 inhibitor that has shown strong single-agent activity in relapsed or refractory (R/R) AML. This phase 1, open-label, sequential group dose-escalation trial (NCT 01390337) is the first evaluating safety and tolerability of quizartinib in combination with SOC chemotherapy in newly diagnosed AML (ndAML)...
February 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29051283/hsp90-inhibition-disrupts-jak-stat-signaling-and-leads-to-reductions-in-splenomegaly-in-patients-with-myeloproliferative-neoplasms
#16
LETTER
Gabriela S Hobbs, Amritha Varshini Hanasoge Somasundara, Maria Kleppe, Rivka Litvin, Maria Arcila, Jihae Ahn, Anna Sophia McKenney, Kristina Knapp, Ryan Ptashkin, Howard Weinstein, Murk-Hein Heinemann, Jasmine Francis, Suzanne Chanel, Ellin Berman, Michael Mauro, Martin S Tallman, Mark L Heaney, Ross L Levine, Raajit K Rampal
No abstract text is available yet for this article.
January 2018: Haematologica
https://www.readbyqxmd.com/read/29046900/us-intergroup-study-of-chemotherapy-plus-dasatinib-and-allogeneic-stem-cell-transplant-in-philadelphia-chromosome-positive-all
#17
Farhad Ravandi, Megan Othus, Susan M O'Brien, Stephen J Forman, Chul S Ha, Jeffrey Y C Wong, Martin S Tallman, Elisabeth Paietta, Janis Racevskis, Geoffrey L Uy, Mary Horowitz, Naoko Takebe, Richard Little, Uma Borate, Partow Kebriaei, Laura Kingsbury, Hagop M Kantarjian, Jerald P Radich, Harry P Erba, Frederick R Appelbaum
This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100...
December 27, 2016: Blood Advances
https://www.readbyqxmd.com/read/28803919/therapy-related-clonal-hematopoiesis-in-patients-with-non-hematologic-cancers-is-common-and-associated-with-adverse-clinical-outcomes
#18
Catherine C Coombs, Ahmet Zehir, Sean M Devlin, Ashwin Kishtagari, Aijazuddin Syed, Philip Jonsson, David M Hyman, David B Solit, Mark E Robson, José Baselga, Maria E Arcila, Marc Ladanyi, Martin S Tallman, Ross L Levine, Michael F Berger
Clonal hematopoiesis (CH), as evidenced by recurrent somatic mutations in leukemia-associated genes, commonly occurs among aging human hematopoietic stem cells. We analyzed deep-coverage, targeted, next-generation sequencing (NGS) data of paired tumor and blood samples from 8,810 individuals to assess the frequency and clinical relevance of CH in patients with non-hematologic malignancies. We identified CH in 25% of cancer patients, with 4.5% harboring presumptive leukemia driver mutations (CH-PD). CH was associated with increased age, prior radiation therapy, and tobacco use...
September 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28801450/genomic-analysis-of-hairy-cell-leukemia-identifies-novel-recurrent-genetic-alterations
#19
Benjamin H Durham, Bartlomiej Getta, Sascha Dietrich, Justin Taylor, Helen Won, James M Bogenberger, Sasinya Scott, Eunhee Kim, Young Rock Chung, Stephen S Chung, Jennifer Hüllein, Tatjana Walther, Lu Wang, Sydney X Lu, Christopher C Oakes, Raoul Tibes, Torsten Haferlach, Barry S Taylor, Martin S Tallman, Michael F Berger, Jae H Park, Thorsten Zenz, Omar Abdel-Wahab
Classical hairy cell leukemia (cHCL) is characterized by a near 100% frequency of the BRAF V600E mutation, whereas ∼30% of variant HCLs (vHCLs) have MAP2K1 mutations. However, recurrent genetic alterations cooperating with BRAF V600E or MAP2K1 mutations in HCL, as well as those in MAP2K1 wild-type vHCL, are not well defined. We therefore performed deep targeted mutational and copy number analysis of cHCL (n = 53) and vHCL (n = 8). The most common genetic alteration in cHCL apart from BRAF V600E was heterozygous loss of chromosome 7q, the minimally deleted region of which targeted wild-type BRAF , subdividing cHCL into those hemizygous versus heterozygous for the BRAF V600E mutation...
October 5, 2017: Blood
https://www.readbyqxmd.com/read/28750565/digging-deeper-in-relapsed-acute-lymphoblastic-leukemia-impact-of-mrd-status-on-outcome-in-second-remission
#20
Mark B Geyer, Martin S Tallman
No abstract text is available yet for this article.
July 28, 2017: Leukemia & Lymphoma
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