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JOURNAL ARTICLE
Jad Othman, Nicola Potter, Adam Ivey, Jelena Jovanovic, Manohursingh Runglall, Sylvie D Freeman, Amanda Frances Gilkes, Ian Thomas, Sean Johnson, Joanna Canham, James Durrell Cavenagh, Panagiotis Kottaridis, Claire Arnold, Hans Beier Ommen, Ulrik Malthe Overgaard, Mike Dennis, Alan K Burnett, Charlotte S Wilhelm-Benartzi, Richard Dilon, Nigel H Russell
Selection of patients with NPM1 mutated AML for allogeneic transplant in 1st complete remission (CR1-allo) remains controversial due to a lack of robust data. Consequently, some centres consider baseline FLT3-ITD an indication for transplant and others rely on measurable residual disease (MRD) status. Using prospective data from the UK NCRI AML17 and AML19 studies, we examined the impact of CR1-allo according to peripheral blood NPM1 MRD status measured by RT-qPCR after 2 courses of induction chemotherapy. Of 737 patients achieving remission, MRD was positive in 19%...
February 16, 2024: Blood
#2
JOURNAL ARTICLE
Julia-Annabell Georgi, Sebastian Stasik, Michael Kramer, Manja Meggendorfer, Christoph Röllig, Torsten Haferlach, Peter Valk, David Linch, Tobias Herold, Nicolas Duployez, Franziska Taube, Jan Moritz Middeke, Uwe Platzbecker, Hubert Serve, Claudia D Baldus, Carsten Muller-Tidow, Claudia Haferlach, Sarah Koch, Wolfgang E Berdel, Bernhard J Woermann, Utz Krug, Jan Braess, Wolfgang Hiddemann, Karsten Spiekermann, Emma L Boertjes, Robert K Hills, Alan Burnett, Gerhard Ehninger, Klaus Metzeler, Maja Rothenberg-Thurley, Annika Dufour, Hervé Dombret, Cecile Pautas, Claude Preudhomme, Laurene Fenwarth, Martin Bornhäuser, Rosemary Gale, Christian Thiede
Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIPInDel ), frameshift InDel or nonsense mutations inducing translational stop (bZIPSTOP ) or single base-pair missense alterations (bZIPms ), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs...
January 16, 2024: Leukemia
#3
JOURNAL ARTICLE
Mhairi Copland, Cono Ariti, Ian F Thomas, Laura Upton, Mia Sydenham, Priyanka Mehta, Shahid Islam, Lars Kjeldsen, Alan K Burnett, Robert K Hills, Nigel Russell, Mike Dennis
Improving outcomes for older patients with acute myeloid leukaemia remains an unmet need. As part of the LI-1 trial, we evaluated lenalidomide (LEN) in combination with low-dose cytosine arabinoside (LDAC) in patients aged >60 years unfit for intensive therapy and compared this to LDAC alone. Two hundred and two patients, randomised 1:1, were evaluable. Overall response rate (CR + CRi) was higher for LDAC + LEN versus LDAC (26% and 13.7% respectively p = 0...
November 28, 2023: British Journal of Haematology
#4
JOURNAL ARTICLE
Francis Mussai, Carmela De Santo, Paul Cheng, Ian F Thomas, Cono Ariti, Laura Upton, Ugo Scarpa, Victoria Stavrou, Mia Sydenham, Alan K Burnett, Steven K Knapper, Priyanka Mehta, Mary F McMullin, Mhairi Copland, Nigel H Russell, Mike Dennis
The survival of acute myeloid leukaemia (AML) patients aged over 60 has been suboptimal historically, whether they are treated using hypomethylating agents, low-dose cytarabine (LDAC) or venetoclax-based regimens. Progress is being made, however, for subgroups with favourable molecular or cytogenetic findings. Arginine metabolism plays a key role in AML pathophysiology. We report the only randomised study of LDAC with recombinant arginase BCT-100 versus LDAC alone in older AML patients unsuitable for intensive therapy...
November 22, 2022: British Journal of Haematology
#5
JOURNAL ARTICLE
Daniel E Goltz, Robert A Burnett, Jay M Levin, Joshua K Helmkamp, John R Wickman, Zoe W Hinton, Claire B Howell, Cynthia L Green, J Alan Simmons, Gregory P Nicholson, Nikhil N Verma, Tally E Lassiter, Oke A Anakwenze, Grant E Garrigues, Christopher S Klifto
BACKGROUND: Recent work has shown inpatient length of stay following shoulder arthroplasty to hold the 2nd strongest association with overall cost (after implant cost itself). In particular, a preoperative understanding for the patients at risk of extended inpatient stay (≥3 days) can allow for counseling, optimization, and anticipating postoperative adverse events. METHODS: A multi-center retrospective review was performed of 5,410 anatomic (52%) and reverse (48%) total shoulder arthroplasties done at two large, tertiary referral health systems...
November 15, 2022: Journal of Shoulder and Elbow Surgery
#6
JOURNAL ARTICLE
Megan Othus, Ian Thomas, Xu Wang, Cono Ariti, Priyanka Mehta, Mia Sydenham, Robert K Hills, Alan K Burnett, Sucha Nand, Sarit Assouline, Laura C Michaelis, Harry P Erba, Nigel Russell, Kathleen F Kerr, Roland B Walter, Mike Dennis
No abstract text is available yet for this article.
October 13, 2022: Leukemia & Lymphoma
#7
JOURNAL ARTICLE
Yanis Tazi, Juan E Arango-Ossa, Yangyu Zhou, Elsa Bernard, Ian Thomas, Amanda Gilkes, Sylvie Freeman, Yoann Pradat, Sean J Johnson, Robert Hills, Richard Dillon, Max F Levine, Daniel Leongamornlert, Adam Butler, Arnold Ganser, Lars Bullinger, Konstanze Döhner, Oliver Ottmann, Richard Adams, Hartmut Döhner, Peter J Campbell, Alan K Burnett, Michael Dennis, Nigel H Russell, Sean M Devlin, Brian J P Huntly, Elli Papaemmanuil
Clinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize and validate 16 molecular classes describing 100% of AML patients. Each class represents diverse biological AML subgroups, and is associated with distinct clinical presentation, likelihood of response to induction chemotherapy, risk of relapse and death over time...
August 8, 2022: Nature Communications
#8
RANDOMIZED CONTROLLED TRIAL
Nigel H Russell, Robert K Hills, Lars Kjeldsen, Richard E Clark, Sahra Ali, Paul Cahalin, Ian F Thomas, Alan K Burnett
The prognosis for younger patients with relapsed acute myeloid leukaemia (AML) is generally dismal. Allogeneic stem cell transplantation is the preferred therapy for these patients. As part of the UK NCRI AML17 trial, daunorubicin/clofarabine (DClo) was compared with fludarabine, cytarabine, granulocyte colony-stimulating factor with idarubicin (FLAG-Ida) in 311 patients designated high-risk following course one of induction therapy, which has previously been reported. We now report the results of the same randomisation in patients who were refractory to two induction courses or subsequently relapsed...
August 2022: British Journal of Haematology
#9
Wei-Yu Lin, Sarah E Fordham, Eric Hungate, Nicola J Sunter, Claire Elstob, Yaobo Xu, Catherine Park, Anne Quante, Konstantin Strauch, Christian Gieger, Andrew Skol, Thahira Rahman, Lara Sucheston-Campbell, Junke Wang, Theresa Hahn, Alyssa I Clay-Gilmour, Gail L Jones, Helen J Marr, Graham H Jackson, Tobias Menne, Mathew Collin, Adam Ivey, Robert K Hills, Alan K Burnett, Nigel H Russell, Jude Fitzgibbon, Richard A Larson, Michelle M Le Beau, Wendy Stock, Olaf Heidenreich, Abrar Alharbi, David J Allsup, Richard S Houlston, Jean Norden, Anne M Dickinson, Elisabeth Douglas, Clare Lendrem, Ann K Daly, Louise Palm, Kim Piechocki, Sally Jeffries, Martin Bornhäuser, Christoph Röllig, Heidi Altmann, Leo Ruhnke, Desiree Kunadt, Lisa Wagenführ, Heather J Cordell, Rebecca Darlay, Mette K Andersen, Maria C Fontana, Giovanni Martinelli, Giovanni Marconi, Miguel A Sanz, José Cervera, Inés Gómez-Seguí, Thomas Cluzeau, Chimène Moreilhon, Sophie Raynaud, Heinz Sill, Maria Teresa Voso, Francesco Lo-Coco, Hervé Dombret, Meyling Cheok, Claude Preudhomme, Rosemary E Gale, David Linch, Julia Gaal-Wesinger, Andras Masszi, Daniel Nowak, Wolf-Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D Milosevic Feenstra, Robert Kralovics, David Grimwade, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsán, Csaba Bödör, Friedrich Stölzel, Kenan Onel, James M Allan
No abstract text is available yet for this article.
January 4, 2022: Nature Communications
#10
JOURNAL ARTICLE
David C Linch, Robert K Hills, Alan K Burnett, Nigel Russell, Rosemary E Gale
Although we earlier reported a very poor outcome for younger adult patients with isocitrate dehydrogenase 2 (IDH2)R172 -mutated acute myeloid leukaemia (AML) entered into UK trials compared to IDH2WT and IDH2R140 -mutated patients, this was not corroborated by a study from the German-Austrian AML Study Group. We have therefore investigated a later cohort of IDH2-mutated patients to identify any changes in outcome and whether this could inform the optimal treatment for IDH2R172 AML. We found an improved outcome for IDH2R172 -mutated AML in the later trials and the data suggests that this may be due to the increased use of allogeneic transplantation to consolidate first remission...
December 6, 2021: British Journal of Haematology
#11
JOURNAL ARTICLE
Wei-Yu Lin, Sarah E Fordham, Eric Hungate, Nicola J Sunter, Claire Elstob, Yaobo Xu, Catherine Park, Anne Quante, Konstantin Strauch, Christian Gieger, Andrew Skol, Thahira Rahman, Lara Sucheston-Campbell, Junke Wang, Theresa Hahn, Alyssa I Clay-Gilmour, Gail L Jones, Helen J Marr, Graham H Jackson, Tobias Menne, Mathew Collin, Adam Ivey, Robert K Hills, Alan K Burnett, Nigel H Russell, Jude Fitzgibbon, Richard A Larson, Michelle M Le Beau, Wendy Stock, Olaf Heidenreich, Abrar Alharbi, David J Allsup, Richard S Houlston, Jean Norden, Anne M Dickinson, Elisabeth Douglas, Clare Lendrem, Ann K Daly, Louise Palm, Kim Piechocki, Sally Jeffries, Martin Bornhäuser, Christoph Röllig, Heidi Altmann, Leo Ruhnke, Desiree Kunadt, Lisa Wagenführ, Heather J Cordell, Rebecca Darlay, Mette K Andersen, Maria C Fontana, Giovanni Martinelli, Giovani Marconi, Miguel A Sanz, José Cervera, Inés Gómez-Seguí, Thomas Cluzeau, Chimène Moreilhon, Sophie Raynaud, Heinz Sill, Maria Teresa Voso, Francesco Lo-Coco, Hervé Dombret, Meyling Cheok, Claude Preudhomme, Rosemary E Gale, David Linch, Julia Gaal-Wesinger, Andras Masszi, Daniel Nowak, Wolf-Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D Milosevic Feenstra, Robert Kralovics, David Grimwade, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsán, Csaba Bödör, Friedrich Stölzel, Kenan Onel, James M Allan
Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8 ; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1...
October 29, 2021: Nature Communications
#12
JOURNAL ARTICLE
Nigel H Russell, Robert K Hills, Abin Thomas, Ian Thomas, Lars Kjeldsen, Mike Dennis, Charles Craddock, Sylvie Freeman, Richard E Clark, Alan K Burnett
Reduced intensity conditioning (RIC) transplantation is increasingly offered to older patients with acute myeloblastic leukemia. We have previously shown that a RIC allograft, particularly from a sibling donor, is beneficial in intermediate-risk patients aged 35-65 years. We here present analyses from the NCRI AML16 trial extending this experience to older patients aged 60-70 inclusive lacking favorable-risk cytogenetics. Nine hundred thirty-two patients were studied, with RIC transplant in first remission given to 144 (sibling n=52, matched unrelated donor n=92) with a median follow-up for survival from complete remission of 60 months...
July 1, 2022: Haematologica
#13
JOURNAL ARTICLE
Mike Dennis, Ian Thomas, Cono Ariti, Laura Upton, Alan K Burnett, Amanda Frances Gilkes, Rohini Radia, Claire Jane Hemmaway, Priyanka Mehta, Steven Knapper, Richard E Clark, Mhairi Copland, Nigel H Russell, Robert K Hills
Survival for older patients with acute myeloid leukaemia (AML) unsuitable for intensive chemotherapy is unsatisfactory. Standard non intensive therapies have low response rates and only extend life by a few months. Quizartinib is an oral Fms-like tyrosine kinase 3 (FLT3) inhibitor with reported activity in wild type patients. As part of the AML LI trial we undertook a randomised evaluation of low dose ara-C (LDAC) with or without quizartinib in patients not fit for intensive chemotherapy. Overall, survival was not improved (202 patients), but in the 27 FLT3-ITD patients the addition of quizartinib to LDAC improved response (p=0...
October 1, 2021: Blood Advances
#14
JOURNAL ARTICLE
Baylie R Hochstedler, Lindsey Burnett, Travis K Price, Carrie Jung, Alan J Wolfe, Linda Brubaker
INTRODUCTION AND HYPOTHESIS: Many clinicians utilize standard culture of voided urine to guide treatment for women with recurrent urinary tract infections (RUTI). However, despite antibiotic treatment, symptoms may persist and events frequently recur. The cyclic nature and ineffective treatment of RUTI suggest that underlying uropathogens pass undetected because of the preferential growth of Escherichia coli. Expanded quantitative urine culture (EQUC) detects more clinically relevant microbes...
March 2022: International Urogynecology Journal
#15
JOURNAL ARTICLE
David C Linch, Robert K Hills, Amanda Gilkes, Alan K Burnett, Nigel Russell, Rosemary E Gale
Outcome after failure of initial therapy in younger adult patients with acute myeloid leukaemia (AML) is highly variable. Cytogenetics, length of first remission (CR1) before relapse, and allogeneic transplantation are known prognostic factors, but the contribution of leukaemic genotype is less clear, particularly in resistant disease. Of 5,651 younger adult patients entered into UK MRC/NCRI AML trials between 1988 and 2014 with available FLT3ITD and NPM1 genotype, 326 (6%) had resistant disease and 2338 (41 %) relapsed after achieving CR1...
March 2, 2021: Leukemia Research
#16
MULTICENTER STUDY
Sabine Kayser, Robert K Hills, Ralitsa Langova, Michael Kramer, Francesca Guijarro, Zuzana Sustkova, Elihu H Estey, Carole M Shaw, Zdeněk Ráčil, Jiri Mayer, Pavel Zak, Maria R Baer, Andrew M Brunner, Tomas Szotkowski, Petr Cetkovsky, David Grimwade, Roland B Walter, Alan K Burnett, Anthony D Ho, Gerhard Ehninger, Carsten Müller-Tidow, Uwe Platzbecker, Christian Thiede, Christoph Röllig, Angela Schulz, Gregor Warsow, Benedikt Brors, Jordi Esteve, Nigel H Russell, Richard F Schlenk, Mark J Levis
In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3-CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16-75) years. AML was de novo in 58%, therapy-related (t-AML) in 37% and secondary after myelodysplastic syndrome (s-AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3-CREBBP, whole-genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9-1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each)...
March 2021: British Journal of Haematology
#17
JOURNAL ARTICLE
Alan K Burnett, Nigel H Russell, Robert K Hills, Stephen Knapper, Sylvie Freeman, Brian Huntly, Richard E Clark, Ian F Thomas, Lars Kjeldsen, Mary Frances McMullin, Mark Drummond, Jonathan Kell, Ruth Spearing
PURPOSE: The optimum number of treatment courses for younger patients with acute myeloid leukemia (AML) is uncertain. The United Kingdom National Cancer Research Institute AML17 trial randomly assigned patients who were not high risk to a total of three versus four courses. PATIENTS AND METHODS: Patients received two induction courses based on daunorubicin and cytarabine (Ara-C), usually with gemtuzumab ozogamicin. Following remission, 1,017 patients were randomly assigned to a third course, MACE (amsacrine, etoposide, and Ara-C), plus a fourth course of MidAc (mitoxantrone and Ara-C) and following an amendment to one or two courses of high-dose Ara-C...
December 23, 2020: Journal of Clinical Oncology
#18
JOURNAL ARTICLE
Qing Zhang, Mintallah Haider, Najla H Al Ali, Jeffrey E Lancet, Pearlie K Epling-Burnette, Alan F List, Eric Padron, Rami S Komrokji
BACKGROUND: Immunosuppressive therapy (IST) yields durable hematologic improvement (HI) in a subset of patients with lower-risk myelodysplastic syndrome (MDS). Age, human leukocyte antigen (HLA)-DR15 positivity, and duration of transfusion dependence are putative clinical variables predictive for response. We investigated the effect of somatic gene mutations on response to IST in lower-risk MDS. PATIENTS AND METHODS: Forty of 66 patients who received antithymocyte globulin with or without cyclosporine A identified at the Moffitt Cancer Center were molecularly profiled using a 49-gene myeloid panel...
June 2020: Clinical Lymphoma, Myeloma & Leukemia
#19
JOURNAL ARTICLE
Richard Dillon, Robert Hills, Sylvie Freeman, Nicola Potter, Jelena Jovanovic, Adam Ivey, Anju Shankar Kanda, Manohursingh Runglall, Nicola Foot, Mikel Valganon, Asim Khwaja, Jamie Cavenagh, Matthew Smith, Hans Beier Ommen, Ulrik Malthe Overgaard, Mike Dennis, Steven Knapper, Harpreet Kaur, David Taussig, Priyanka Mehta, Kavita Raj, Igor Novitzky-Basso, Emmanouil Nikolousis, Robert Danby, Pramila Krishnamurthy, Kate Hill, Damian Finnegan, Samah Alimam, Erin Hurst, Peter Johnson, Anjum Khan, Rahuman Salim, Charles Craddock, Ruth Spearing, Amanda Gilkes, Rosemary Gale, Alan Burnett, Nigel H Russell, David Grimwade
Relapse remains the most common cause of treatment failure for patients with acute myeloid leukemia (AML) who undergo allogeneic stem cell transplantation (alloSCT), and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry before alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays, which have far greater sensitivity. We analyzed pretransplant blood and bone marrow samples by reverse-transcription polymerase chain reaction in 107 patients with NPM1-mutant AML enrolled in the UK National Cancer Research Institute AML17 study...
February 27, 2020: Blood
#20
REVIEW
Alan K Burnett, Robert K Hills, Nigel Russell
No abstract text is available yet for this article.
January 2020: British Journal of Haematology
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