Article
Medicine, General & Internal
Courtney D. Dinardo, Harry P. Erba, Sylvie D. Freeman, Andrew H. Wei
Summary: Progress in acute myeloid leukaemia treatment has seen significant improvements in scientific understanding, prognostication tools, risk assessments, and incorporation of measurable residual disease into risk assessments. Recent updates in classification and recommendations by organizations such as WHO, ICC, and European LeukemiaNet have provided enhanced guidance for prognostic stratification and treatment response assessment. There have also been advancements in treatment options, leading to improved outcomes for both newly diagnosed and relapsed patients.
Review
Medicine, General & Internal
V. Lj. Lazarevic
Summary: The definition of older age in AML is arbitrary, with various age thresholds used in clinical studies. Treatment decisions for older AML patients should be personalized and shared through dialogue with patients and their families. Despite advances in research and therapy, curing older patients with AML remains a challenge.
JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Hematology
Anne E. Bras, Zgjim Osmani, Valerie de Haas, Mojca Jongen-Lavrencic, Jeroen G. te Marvelde, C. Michel Zwaan, Ester Mejstrikova, Paula Fernandez, Tomasz Szczepanski, Alberto Orfao, Jacques J. M. van Dongen, Vincent H. J. van der Velden
Summary: In this study, a robust flow cytometric definition for myeloperoxidase (MPO) positivity was established based on standardised protocols and multicentre acute leukaemia cases, achieving the best diagnostic performance by defining MPO positivity as >= 20% of the acute leukaemia cells exceeding a lymphocyte-based threshold. This methodology should be applicable to any form of standardised flow cytometry.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Weidong Ding, Yun Ling, Yuan Shi, Zhuojun Zheng
Summary: This study established a lncRNA prognostic model for predicting the survival of acute myeloid leukemia (AML) patients and demonstrated its accuracy and reliability through verification.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Pathology
Riana van der Linder, Sandy Smith, David A. Brown, Sarah C. Sasson, Elizabeth Tegg
Summary: We investigated the use of multidimensional plots (MD-MFC) for acute myeloid leukaemia (AML) minimal residual disease (MRD) monitoring and compared the results with two-dimensional flow cytometry (2D-MFC) and molecular methods. The correlation between MD-MFC and 2D-MFC was good, while there was no correlation between MFC and molecular methods. MD-MFC can be a feasible alternative for AML MRD monitoring.
Article
Oncology
Anne E. Bras, Sergio Matarraz, Stefan Nierkens, Paula Fernandez, Jan Philippe, Carmen-Mariana Aanei, Fabiana Vieira de Mello, Leire Burgos, Alita J. Van der Sluijs-Gelling, Georgiana Emilia Grigore, Jacques J. M. van Dongen, Alberto Orfao, Vincent H. J. van der Velden
Summary: Flow cytometry plays an important role in the diagnosis of acute myeloid leukemia. This study reports on the construction of a large database of acute myeloid leukemia patients and discusses the quality assessment procedure used. The study shows that obtaining reproducible flow cytometric data across centers is feasible with strict quality assessment.
Article
Cell Biology
Shenghao Hua, Tao Feng, Lei Yin, Qi Wang, Xuejun Shao
Summary: The study showed that NEDD9 overexpression in AML is associated with specific pathological classifications, genetic mutations, and prognosis. Patients with NEDD9 overexpression may benefit from HSCT. Additionally, miR-381 was identified as a potential therapeutic target by directly targeting NEDD9.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Rachel M. Koldej, Ashvind Prabahran, Chin Wee Tan, Ashley P. Ng, Melissa J. Davis, David S. Ritchie
Summary: HCL is a rare B cell malignancy characterized by hairy B cells and extensive BM infiltration. Treatment with CDA leads to variable response duration. Analysis of the BM microenvironment identified prognostic biomarkers of response to CDA, with dysregulated expression of immune markers pre- and post-CDA treatment. Duration of response was associated with reduction in tumor burden and increased CD8 T cell infiltration into the BM post-CDA.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Jochen Greiner, Elliott Brown, Lars Bullinger, Robert K. Hills, Vanessa Morris, Hartmut Doehner, Ken I. Mills, Barbara-ann Guinn
Summary: This study found that BIRC5 expression plays a role in the survival of AML patients, with above median levels associated with improved overall survival but not reaching statistical significance. Adjusted analyses showed a beneficial effect of high BIRC5 levels on overall survival. Additionally, decreased BIRC5 expression was associated with better clinical outcome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Marijana Miljkovic-Licina, Nicolas Arraud, Aicha Dorra Zahra, Patricia Ropraz, Thomas Matthes
Summary: Extracellular vesicles (EVs) are lipid-bound vesicles secreted by cells. They play a crucial role in cell-to-cell communication by transporting various molecules. In the case of acute leukemia, EVs produced by cancer cells can impact the surrounding microenvironment and contribute to disease progression. Our study utilized different methods to quantify and characterize EVs from acute leukemia patients, providing insights into their functional role in leukemia development and their potential as therapy targets and disease biomarkers.
Article
Immunology
Nan Xu, Kai Sun, Ya-Zhe Wang, Wen-Min Chen, Jun Wang, Ling-Di Li, Xu Wang, Yue Hao, Yan Chang, Yan-Rong Liu, Xiao-Jun Huang, Ya-Zhen Qin
Summary: The transcript level of IL7R in bone marrow at diagnosis is predictive of relapse risk in t(8;21) AML, and this may be attributed to differences in the quantity, status, and function of T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Wu Ye, Mingzhu Ma, Xia Wu, Jili Deng, Xiaoyan Liu, Xue Zheng, Yuping Gong
Summary: A meta-analysis was conducted to evaluate the prognostic value of KMT2A-PTD in patients with AML. The results showed that KMT2A-PTD was associated with shorter overall survival in the total population, as well as in karyotypically normal AML and old AML patients. KMT2A-PTD may serve as a promising genetic biomarker for AML patients in the future.
Article
Medical Laboratory Technology
Samiha Jaddaoui, Hanaa Bencharef, Mouna Lamchahab, Asmaa Quessar, Bouchra Oukkache
Summary: The study demonstrates that the phenotype of CD34+CD38-CD123+ combined with aberrant phenotype detection of HLA DR and CD117 markers on stem cells contributes to detecting LSCs, indicating poor prognosis in AML patients.
CLINICAL LABORATORY
(2022)
Article
Medicine, General & Internal
Horia Bumbea, Ana Maria Vladareanu, Ion Dumitru, Viola Maria Popov, Cristina Ciufu, Anca Nicolescu, Minodora Onisai, Cristina Marinescu, Diana Cisleanu, Irina Voican, Sinziana Sarghi
Summary: This study found that patients with acute myeloid leukemia (AML) have impaired platelet function, characterized by changes in adhesion receptors and activation markers. Flow cytometry can effectively identify multiple functional platelet impairments in AML pathogenesis.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Jie Xu, Fan Song, Huijue Lyu, Mikoto Kobayashi, Baozhen Zhang, Ziyu Zhao, Ye Hou, Xiaotao Wang, Yu Luan, Bei Jia, Lena Stasiak, Josiah Hiu-yuen Wong, Qixuan Wang, Qi Jin, Qiushi Jin, Yihao Fu, Hongbo Yang, Ross C. Hardison, Sinisa Dovat, Leonidas C. Platanias, Yarui Diao, Yue Yang, Tomoko Yamada, Aaron D. Viny, Ross L. Levine, David Claxton, James R. Broach, Hong Zheng, Feng Yue
Summary: This study uses Hi-C and whole-genome sequencing to analyze samples from AML patients and healthy donors, revealing recurrent and subtype-specific alterations in chromatin structure and loops. Functional validation and manipulation of DNA methylation further highlight the role of repressive loops and hijacked cis elements in AML.
Article
Hematology
Stephane de Botton, Pau Montesinos, Andre C. Schuh, Cristina Papayannidis, Paresh Vyas, Andrew H. Wei, Hans Ommen, Sergey Semochkin, Hee-Je Kim, Richard A. Larson, Jaime Koprivnikar, Olga Frankfurt, Felicitas Thol, Joerg Chromik, Jenny Byrne, Arnaud Pigneux, Xavier Thomas, Olga Salamero, Maria Belen Vidriales, Vadim Doronin, Hartmut Doehner, Amir T. Fathi, Eric Laille, Xin Yu, Maroof Hasan, Patricia Martin-Regueira, Courtney D. DiNardo
Summary: This study compared the efficacy of the oral IDH2 inhibitor enasidenib with conventional care regimens (CCR) in older patients with late-stage mutant-IDH2 AML. Enasidenib significantly improved event-free survival, time to treatment failure, overall response rate, hematologic improvement, and transfusion independence compared to CCR. However, there was no significant difference in overall survival, possibly due to early dropout and subsequent AML-directed therapies.
Article
Hematology
Priyanka Mehta, Nick Telford, Chris Wragg, Richard Dillon, Sylvie Freeman, Damian Finnegan, Angela Hamblin, Mhairi Copland, Steve Knapper
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Hematology
Robert K. Hills
Summary: Prolonged cytopaenia is a recognized issue after CAR-T cell therapy, but the causes and implications are still unknown. Kitamura et al.'s study identified that alterations in the bone marrow niche prior to CAR-T therapy may be a potential predictor for long-term cytopaenia, shedding light on this serious side-effect of treatment.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Medicine, General & Internal
Courtney D. Dinardo, Harry P. Erba, Sylvie D. Freeman, Andrew H. Wei
Summary: Progress in acute myeloid leukaemia treatment has seen significant improvements in scientific understanding, prognostication tools, risk assessments, and incorporation of measurable residual disease into risk assessments. Recent updates in classification and recommendations by organizations such as WHO, ICC, and European LeukemiaNet have provided enhanced guidance for prognostic stratification and treatment response assessment. There have also been advancements in treatment options, leading to improved outcomes for both newly diagnosed and relapsed patients.
Article
Hematology
Jad Othman, Charlotte Wilhelm-Benartzi, Richard Dillon, Steve Knapper, Sylvie D. Freeman, Leona M. Batten, Joanna Canham, Emily L. Hinson, Julie Wych, Sophie Betteridge, William Villiers, Michelle Kleeman, Amanda Gilkes, Nicola Potter, Ulrik Malthe Overgaard, Priyanka Mehta, Panagiotis Kottaridis, Jamie Cavenagh, Claire Hemmaway, Claire Arnold, Mike Dennis, Nigel H. Russell
Summary: This study compared the efficacy of CPX-351 and FLAG-Ida in younger patients, and found no significant difference in overall survival between the two treatments. However, the use of CPX-351 significantly prolonged relapse-free survival, particularly in patients with MDS-related gene mutations.
Review
Hematology
Eduard Schulz, Peter D. Aplan, Sylvie D. Freeman, Steven Z. Pavletic
Summary: Approximately 90% of MDS patients have oncogenic somatic mutations, and the genetic risk stratification and diagnosis criteria have improved. Monitoring MRD has been used in leukemias but not yet defined for MDS. This article discusses the evidence, challenges, and framework for integrating MRD into MDS treatment and clinical trials.
Article
Hematology
Justin Loke, Nicholas McCarthy, Aimee Jackson, Shamyla Siddique, Andrea Hodgkinson, John Mason, Charles Crawley, Maria Gilleece, Andrew Peniket, Rachel Protheroe, Rahuman Salim, Eleni Tholouli, Keith Wilson, Georgia Andrew, Richard Dillon, Naeem Khan, Victoria Potter, Pramila Krishnamurthy, Charles Craddock, Sylvie Freeman
Summary: This study reports the prognostic impact of biomarkers including MRD, T-cell chimerism, and blast HLA-DR expression in AML/MDS patients receiving allogeneic stem-cell transplant. MRD positivity is associated with reduced overall survival, while MRD is infrequent and does not affect the outcome in patients with full donor T-cell chimerism.
Article
Hematology
Sylvie D. Freeman, Abin Thomas, Ian Thomas, Robert K. Hills, Paresh Vyas, Amanda Gilkes, Marlen Metzner, Niels Asger Jakobsen, Alison Kennedy, Rachel Moore, Nuria Marquez Almuina, Sarah Burns, Sophie King, Georgia Andrew, Kathleen M. E. Gallagher, Rob S. Sellar, Paul Cahalin, Duruta Weber, Mike Dennis, Priyanka Mehta, Steven Knapper, Nigel H. Russell
Summary: Addition of gemtuzumab ozogamicin to induction chemotherapy improves outcomes in older AML patients, especially those with MRD<0.1% and IDH mutations. The survival advantage from this treatment is dependent on allogeneic transplantation.
Article
Hematology
Peter Hokland, Isolda I. Fernandez, Sylvie D. Freeman, Bjorn T. Gjertsen, Jie Jin, Vidh Murthy, Masamitsu Yanada, Arnold Ganser
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Hematology
Robert K. Hills
Summary: The paper by Noor et al. presents significant findings on the incidence and outcomes of patients with acute myeloid leukaemia in Afghanistan. It highlights the lower age of patients compared to the Western standard, reflecting the unique demographics of the country. These findings serve as an important initial step in identifying areas for improvement.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Naval G. Daver, Paresh Vyas, Suman Kambhampati, Monzr M. Al Malki, Richard A. Larson, Adam S. Asch, Gabriel Mannis, Wanxing Chai-Ho, Tiffany N. Tanaka, Terrence J. Bradley, Deepa Jeyakumar, Eunice S. Wang, Kendra Sweet, Hagop M. Kantarjian, Guillermo Garcia-Manero, Rami Komrokji, Guan Xing, Giridharan Ramsingh, Camille Renard, Joshua F. Zeidner, David A. Sallman
Summary: Magrolimab combined with azacitidine showed promising efficacy and tolerability in patients with untreated AML ineligible for intensive chemotherapy, including those with TP53 mutations.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Jad Othman, Nicola Potter, Katya Mokretar, David Taussig, Anjum Khan, Pramila Krishnamurthy, Anne-Louise Latif, Paul Cahalin, James Aries, Mariam Amer, Edward Belsham, Eibhlin Conneally, Charles Craddock, Dominic Culligan, Mike Dennis, Caroline Duncan, Sylvie D. Freeman, Caroline Furness, Amanda Gilkes, Paraskevi Gkreka, Katherine Hodgson, Wendy Ingram, Manish Jain, Andrew King, Steven Knapper, Panagiotis Kottaridis, Mary Frances McMullin, Unmesh Mohite, Loretta Ngu, Jenny O'Nions, Katharine Patrick, Tom Rider, Wing Roberts, Marianne Tang Severinsen, Neill Storrar, Tom Taylor, Nigel H. Russell, Richard Dillon
Summary: Patients with FLT3-mutated AML are at high risk of relapse and poor outcomes. Monitoring measurable residual disease (MRD) can help identify patients destined to relapse, providing an opportunity for pre-emptive intervention. In this study, 56 patients with molecular failure were treated with FLT3 inhibitors (FLT3i), resulting in a molecular response rate of 60% and an overall survival rate of 80% at 2 years. High-sensitivity next-generation sequencing identified patients more likely to benefit from FLT3i monotherapy. Further prospective studies are warranted to evaluate this promising treatment strategy.
Article
Hematology
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
Summary: Improving outcomes for older patients with acute myeloid leukaemia is still an unmet need. In this study, we evaluated the effectiveness of lenalidomide in combination with low-dose cytosine arabinoside compared to low-dose cytosine arabinoside alone in unfit patients aged over 60. The combination therapy showed a higher overall response rate, but there was no difference in overall survival between the two arms.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Rory M. Shallis, Naval Daver, Jessica K. Altman, Rami S. Komrokji, Daniel A. Pollyea, Talha Badar, Jan P. Bewersdorf, Vijaya R. Bhatt, Stephane de Botton, Adolfo de la Fuente Burguera, Hetty E. Carraway, Pinkal Desai, Richard Dillon, Nicolas Duployez, Firas El Chaer, Amir T. Fathi, Sylvie D. Freeman, Ivana Gojo, Michael R. Grunwald, Brian A. Jonas, Marina Konopleva, Tara L. Lin, Gabriel N. Mannis, John Mascarenhas, Laura C. Michaelis, Alice S. Mims, Pau Montesinos, Olga Pozdnyakova, Keith W. Pratz, Andre C. Schuh, Mikkael A. Sekeres, Catherine C. Smith, Maximilian Stahl, Marion Subklewe, Geoffrey L. Uy, Maria Teresa Voso, Roland B. Walter, Eunice S. Wang, Joshua F. Fzeidner, Andrius Zucenka, Amer M. Zeidan
Summary: The coexistence of two acute myeloid leukaemia classification systems, proposed by the WHO and the International Consensus Classification in 2022, raises concerns due to consequential disagreements on the diagnosis of acute myeloid leukaemia. This problem threatens the ability of healthcare providers to diagnose and manage the condition, with potential negative impacts on clinical trials, response assessments, and drug development. This viewpoint reviews the merits and limitations of both classification systems and proposes a roadmap for harmonization.
LANCET HAEMATOLOGY
(2023)
