Review
Oncology
Michael Loschi, Pierre Fenaux, Thomas Cluzeau
Summary: TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are characterized by poor prognosis. In this review, we analyze the prognosis of these diseases, focusing on the extent of TP53 mutation status and its correlation with cytogenetic complexity. We discuss the potential improvement in outcome based on recent results obtained with new drugs (especially eprenetapopt and magrolimab). The impact of allogeneic hematopoietic stem cell transplantation (aHSCT) and post-transplantation treatment is also emphasized.
Review
Oncology
Li Xuan, Qifa Liu
Summary: Relapse is still the main reason for treatment failure in AML patients undergoing allo-HSCT. Evidence suggests that maintenance therapy post-transplantation, particularly targeted drugs like hypomethylating agents, FLT3 inhibitors, and isocitrate dehydrogenase inhibitors, could benefit AML patients, especially those at high risk.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Medicine, General & Internal
Petter S. Woll, Tetsuichi Yoshizato, Eva Hellstrom-Lindberg, Thoas Fioretos, Benjamin L. Ebert, Sten Eirik W. Jacobsen
Summary: The genetic architecture of cancer has been extensively studied, leading to the identification of new therapeutic targets and the development of promising treatment strategies. However, disease progression, relapse, and treatment-related mortality remain challenging in certain types of cancer such as myelodysplastic syndromes and acute myeloid leukemia. The persistence of rare leukemic stem cells following therapy underscores the resistance mechanisms of these cells and their role in relapse. To improve treatment strategies, there is a need to better understand and characterize the stem cells associated with these diseases at the cellular, molecular, and genetic levels.
JOURNAL OF INTERNAL MEDICINE
(2022)
Review
Hematology
Pongthep Vittayawacharin, Piyanuch Kongtim, Stefan O. Ciurea
Summary: Myelodysplastic syndromes (MDS) are a group of diverse hematopoietic stem cell tumors primarily affecting older individuals, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment. In recent years, the use of reduce-intensity conditioning regimens and haploidentical donors for transplantation has improved treatment outcomes. However, treatment-related mortality remains a limitation, highlighting the importance of pre-transplant evaluation for older patients.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Guillermo Garcia-Manero, Valeria Santini, Antonio Almeida, Uwe Platzbecker, Anna Jonasova, Lewis R. Silverman, Jose Falantes, Gianluigi Reda, Francesco Buccisano, Pierre Fenaux, Rena Buckstein, Maria Diez Campelo, Stephen Larsen, David Valcarcel, Paresh Vyas, Valentina Giai, Esther Natalie Oliva, Jake Shortt, Dietger Niederwieser, Moshe Mittelman, Luana Fianchi, Ignazia La Torre, Jianhua Zhong, Eric Laille, Daniel Lopes de Menezes, Barry Skikne, C. L. Beach, Aristoteles Giagounidis
Summary: CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. However, more early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further evaluation of CC-486 in MDS is needed.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Oncology
Sargam Kapoor, Grace Champion, Aparna Basu, Anu Mariampillai, Matthew J. Olnes
Summary: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow with poor prognosis. Recent advancements in immune therapies, including immune suppressive therapy and novel treatments like monoclonal antibodies and cellular therapeutics, have shown promise in treating these diseases.
Article
Medicine, Research & Experimental
Na Man, Gloria Mas, Daniel L. Karl, Jun Sun, Fan Liu, Qin Yang, Miguel Torres-Martin, Hidehiro Itonaga, Concepcion Martinez, Shi Chen, Ye Xu, Stephanie Duffort, Pierre-Jacques Hamard, Chuan Chen, Beth E. Zucconi, Luisa Cimmino, Feng-Chun Yang, Mingjiang Xu, Philip A. Cole, Maria E. Figueroa, Stephen D. Nimer
Summary: This study identified a tumor suppressor role of the acetyltransferase p300 in MDS, with loss of p300 enhancing HSPC proliferation and self-renewal, ultimately increasing leukemogenicity. Mechanistically, loss of p300 altered gene expression and promoted leukemia development, while activating p300 activity countered these effects. This suggests a potential therapeutic application of p300 activators in treating MDS with TET2 mutations.
Review
Biochemistry & Molecular Biology
Carmine Liberatore, Mauro Di Ianni
Summary: The management of relapsed acute myeloid leukemia (AML) post allogeneic hematopoietic stem cell transplantation (HSCT) remains a clinical challenge. Hypomethylating agents (HMAs) have become the standard therapeutic approach due to favorable tolerability and their ability to be combined with other anti-leukemic agents. The addition of donor lymphocytes infusions (DLI) generally leads to improved outcomes, while the introduction of novel targeted drugs offers new possibilities in salvage regimens.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Thomas Cluzeau, Michael Loschi, Pierre Fenaux, Rami Komrokji, David A. Sallman
Summary: This article reviews the progress in targeting TP53 mutated myelodysplastic syndromes and acute myeloid leukemia, focusing on the use of active agents and future treatment directions. It emphasizes the importance of understanding the clinical characteristics of the disease and the impact of TP53 mutant burden on patient clinical trajectory.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Masamitsu Yanada, Shohei Mizuno, Satoshi Yamasaki, Kaito Harada, Takaaki Konuma, Hiroya Tamaki, Naoki Shingai, Naoyuki Uchida, Yukiyasu Ozawa, Masatsugu Tanaka, Makoto Onizuka, Masashi Sawa, Hirohisa Nakamae, Souichi Shiratori, Ken-ichi Matsuoka, Tetsuya Eto, Toshiro Kawakita, Yumiko Maruyama, Tatsuo Ichinohe, Yoshinobu Kanda, Yoshiko Atsuta, Jun Aoki, Shingo Yano
Summary: The study compared outcomes of allogeneic hematopoietic cell transplantation for de novo AML, AML evolving from MDS, and MDS-EB, showing significant differences in overall survival probabilities. Higher risks of non-relapse mortality and relapse were associated with AML evolving from MDS and MDS-EB, indicating the need to reduce these risks for improved outcomes.
LEUKEMIA & LYMPHOMA
(2021)
Review
Cell Biology
Yasmin Abaza, Amer M. Zeidan
Summary: Immune checkpoint inhibitors have had a significant impact on the treatment of solid tumors, but there has been limited progress in myeloid malignancies. The low mutational burden of acute myeloid leukemia is a potential reason for the lack of response to T-cell harnessing ICIs. Targeting agents, such as magrolimab and sabatolimab, in combination with other drugs, have shown promising activity in early clinical trials.
Review
Oncology
Romane Joudinaud, Thomas Boyer
Summary: MDS and AML transformation is supported by alterations affecting malignant stem cells, including metabolic, phenotypic, and genetic characteristics. MDS-SCs are more likely derived from healthy HSCs, while LSCs may originate from healthy progenitors like LMPP. Overexpression of CD123 and CLL1 markers is seen in high risk-MDS, leading to exciting therapeutic applications.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Hong Wang, Qingyuan Wang, Jiaqian Qi, Xueqian Li, Tiantian Chu, Huiying Qiu, Chengcheng Fu, Xiaowen Tang, Changgeng Ruan, Depei Wu, Yue Han
Summary: The study aimed to evaluate the impact of different pre-transplant therapies and transplantation interval times on the prognosis of patients with myelodysplastic syndromes (MDS). The results showed that there were no significant differences in overall survival (OS) and relapse-free survival (RFS) between patients who received hypomethylating agents (HMAs) or supportive care (SC), except for a lower rate of non-relapse mortality in the HMA-treated group. Compared to patients who received HMA, those who received chemotherapy-based therapy had a lower OS rate and a slightly higher non-relapse mortality rate. The early transplant group (transplant interval <6 months) had better OS and lower non-relapse mortality compared to the delayed transplant group (transplant interval >= 6 months).
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Sayantanee Dutta, Jennifer Moritz, Gudrun Pregartner, Gerhard G. Thallinger, Ilona Brandstaetter, Karin Lind, Simin Rezania, Freya Lyssy, Andreas Reinisch, Armin Zebisch, Andrea Berghold, Albert Woelfler, Heinz Sill
Summary: The study found TP53 aberrations to be common in AML and MDS patients, with similar clinical and cytogenetic characteristics, but higher overall survival in MDS patients compared to AML patients. High transformation rate of TP53 aberrant MDS reduces survival probability for patients.
ANNALS OF HEMATOLOGY
(2022)
Article
Medicine, General & Internal
Huan Li, Fang Hu, Robert Peter Gale, Mikkael A. Sekeres, Yang Liang
Summary: Myelodysplastic syndromes (MDS) are a group of blood cancers characterized by dysregulated hematopoiesis and risk of transformation to acute myeloid leukemia. Prognostic systems can predict survival in MDS patients. Treatment goals differ for low-risk and high-risk MDS, with the aim to improve quality of life and prolong survival, respectively. Hematopoietic cell transplantation can cure MDS, but it is not widely used.
NATURE REVIEWS DISEASE PRIMERS
(2022)
Article
Oncology
Victoria Stavrou, Livingstone Fultang, Sarah Booth, Daniele De Simone, Arekdiusz Bartnik, Ugo Scarpa, Luciana Gneo, Silvia Panetti, Sandeep Potluri, Meaad Almowaled, Jonathan Barlow, Andris Jankevics, Gavin Lloyd, Andrew Southam, David A. Priestman, Paul Cheng, Warwick Dunn, Frances Platt, Hitoshi Endou, Charles Craddock, Karen Keeshan, Francis Mussai, Carmela De Santo
Summary: Acute myeloid leukaemia (AML) creates an immunosuppressive environment through induced arginine depletion. Serum amyloid A (SAA) in AML upregulates ARG2 expression, promotes cell viability, and activates iNKT cells, resulting in AML cell death. Therefore, stimulating iNKT cell activity has potential as an immunotherapy for AML.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Hematology
Warren B. Fingrut, Boglarka Gyurkocza, Jessica Flynn, Eric Davis, Sean Devlin, Andromachi Scaradavou, Stephanie Chinapen, Sean Quach, Christina Cho, Sergio A. Giralt, Ann A. Jakubowski, Richard J. Lin, Esperanza B. Papadopoulos, Miguel-Angel Perales, Doris Ponce, Brian C. Shaffer, Roni Tamari, James W. Young, Ioannis Politikos, Juliet N. Barker
Summary: This study examined the impact of recipient ancestry on the time to allogeneic transplant in patients with acute myelogenous leukemia (AML). Non-European ancestry patients were more likely to receive HLA-mismatched donor allografts and had delays in the transplantation process compared to European patients. The pandemic further exacerbated these delays for non-European patients.
Article
Hematology
Doris M. Ponce, Amin M. Alousi, Ryotaro Nakamura, John Slingerland, Marco Calafiore, Karamjeet S. Sandhu, Juliet N. Barker, Sean Devlin, Jinru Shia, Sergio Giralt, Miguel-Angel Perales, Gillian Moore, Samira Fatmi, Cristina Soto, Antonio Gomes, Paul Giardina, LeeAnn Marcello, Xiaoqiang Yan, Tom Tang, Kevin Dreyer, Jianmin Chen, William L. Daley, Jonathan U. Peled, Marcel R. M. van den Brink, Alan M. Hanash
Summary: This study evaluated the safety and efficacy of a novel recombinant human interleukin-22 dimer, F-652, in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD. The results showed that 70% of patients achieved a satisfactory treatment response, demonstrating the potential effect of this combination therapy for improving GVHD-associated dysbiosis.
Article
Hematology
Oliver Van Oekelen, Karthik Nath, Tarek H. Mouhieddine, Tasmin Farzana, Adolfo Aleman, David T. Melnekoff, Yogita Ghodke-Puranik, Gunjan L. Shah, Alexander Lesokhin, Sergio Giralt, Santiago Thibaud, Adriana Rossi, Cesar Rodriguez, Larysa Sanchez, Joshua Richter, Shambavi Richard, Hearn J. Cho, Ajai Chari, Saad Z. Usmani, Sundar Jagannath, Urvi A. Shah, Sham Mailankody, Samir Parekh
Summary: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR T) therapy has shown remarkable efficacy in relapsed/refractory multiple myeloma patients. However, most patients eventually relapse despite high initial response rates. This study analyzed the salvage treatments and outcomes of patients with disease recurrence after BCMA-directed CAR T therapy.
Article
Biophysics
Miriam Sanchez-Escamilla, Jessica Flynn, Sean Devlin, Molly Maloy, Samira A. Fatmi, Ana Alarcon Tomas, Silvia Escribano-Serrat, Doris Ponce, Craig S. Sauter, Sergio A. Giralt, Michael Scordo, Miguel-Angel Perales
Summary: The Endothelial Activation and Stress Index (EASIX) is a prognostic tool that predicts non-relapse mortality (NRM) and overall survival (OS) at the onset of acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). This study evaluated the EASIX score at different time points pre- and post-HCT and found that high EASIX scores were significantly associated with poorer overall outcomes, independent of other factors. EASIX provides an independent and easily accessible tool to predict outcomes for patients undergoing HCT.
BONE MARROW TRANSPLANTATION
(2023)
Article
Hematology
Rohtesh S. Mehta, David Marin, Amin Alousi, Christopher G. Kanakry, Richard E. Champlin, Katayoun Rezvani, Elizabeth J. Shpall, Kristin Page, Shahinaz M. Gadalla, Daniel Weisdorf, Partow Kebriaei
Summary: In adult patients with acute lymphoblastic leukemia, younger haploidentical donors have better overall survival compared to older HLA-matched unrelated donors. Donor age is a prognostic factor for survival in hematopoietic cell transplantation.
Letter
Biophysics
Meera Mohan, Siegfried Janz, Ruta Brazauskas, Michael B. Dwinell, Bi Qing Teng, Grant Yun, Jing Dong, Marcelo C. Pasquini, Sergio Giralt, Heather Landau, Edward Stadtmauer, Amrita Krishnan, Anita D'Souza
BONE MARROW TRANSPLANTATION
(2023)
Article
Hematology
Roni Tamari, Donal P. Mclornan, Kwang Woo Ahn, Noel Estrada-Merly, Juan Carlos Hernandez-Boluda, Sergio Giralt, Jeanne Palmer, Robert Peter Gale, Zachariah Defilipp, David I. Marks, Marjolein van der Poel, Leo F. Verdonck, Minoo Battiwalla, Miguel Angel Diaz, Vikas Gupta, Haris Ali, Mark Robert Litzow, Hillard M. Lazarus, Usama Gergis, Asad Bashey, Jane Liesveld, Shahrukh Hashmi, Jeffrey J. Pu, Amer Beitinjaneh, Christopher Bredeson, David Rizzieri, Bipin N. Savani, Muhammad Bilal Abid, Siddhartha Ganguly, Vaibhav Agrawal, Vera Ulrike Bacher, Baldeep Wirk, Tania Jain, Corey Cutler, Mahmoud Aljurf, Tamila Kindwall-Keller, Mohamed A. Kharfan-Dabaja, Gerhard C. Hildebrandt, Attaphol Pawarode, Melhem M. Solh, Jean A. Yared, Michael R. Grunwald, Sunita Nathan, Taiga Nishihori, Sachiko Seo, Bart L. Scott, Ryotaro Nakamura, Betul Oran, Tomasz Czerw, Ibrahim Yakoub-Agha, Wael Saber
Summary: A prognostic model was developed for myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation. Factors such as patient age, donor compatibility, and hemoglobin levels were found to be associated with mortality risk. The proposed scoring system could accurately predict overall survival and transplant-related mortality in two large cohorts.
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
Biophysics
Christina Cho, Sean Devlin, Molly Maloy, Mary M. Horowitz, Brent Logan, J. Douglas Rizzo, Sergio A. Giralt, Miguel-Angel Perales
Summary: The Web-based One Year Survival Outcomes Calculator developed by the Center for International Blood and Marrow Transplant Research (CIBMTR) can provide individualized estimates of 1-year overall survival (OS) probability after allogeneic hematopoietic cell transplant (HCT) and is useful for personalized patient counseling. In a retrospective study, the calibration of the CIBMTR Calculator was assessed among adult recipients of first allogeneic HCT for AML, ALL, or MDS. The study showed that the CIBMTR Calculator can accurately predict 1-year survival in larger patient cohorts.
BONE MARROW TRANSPLANTATION
(2023)
Article
Biophysics
Enrico Maffini, Maud Ngoya, Jacques-Emmanuel Galimard, Samia Harbi, Nicolaus Kroeger, Uwe Platzbecker, Henrik Sengeloev, Charles Craddock, Victoria Potter, Goda Choi, Patrice Chevallier, Friedrich Stolzel, Eleni Tholouli, Johan Maertens, Fabio Ciceri, Jan Cornelissen, Jaime Sanz, Alexandros Spyridonidis, Francesco Lanza, Arnon Nagler, Mohamad Mohty
Summary: Allogeneic HCT programs are becoming accessible for older AML patients. Patients aged ≥70 years who received HCT from matched sibling, unrelated, or haploidentical donors showed good clinical outcomes, with reduced relapse rates and improved leukemia-free survival in haploidentical and unrelated donor transplantations compared to matched sibling transplantation.
BONE MARROW TRANSPLANTATION
(2023)
Article
Pharmacology & Pharmacy
Allison Gaudy, Eric Laille, Rochelle Bailey, Simon Zhou, Barry Skikne, C. L. Beach
Summary: Researchers developed a population pharmacokinetic model to characterize the concentration-time profiles of oral azacitidine (AZA) in patients with AML, myelodysplastic syndrome, or chronic myelomonocytic leukemia. The study found that exposure parameters of oral-AZA were significantly associated with relapse-free survival, overall survival, and adverse events. The optimal dosing schedule for oral-AZA maintenance was determined to be 300 mg once daily for 14 days.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pediatrics
Alba Rubio-San-Simon, Natasha K. A. van Eijkelenburg, Raoull Hoogendijk, Henrik Hasle, Charlotte M. Niemeyer, Michael N. Dworzak, Marco Zecca, Marta Lopez-Yurda, Julie M. Janssen, Alwin D. R. Huitema, Marry M. van den Heuvel-eibrink, Eric J. Laille, Harm van Tinteren, Christian M. Zwaan
Summary: This study aimed to evaluate the safety, pharmacokinetics, and efficacy of azacitidine in children with relapsed MDS/JMML prior to a second hematopoietic stem cell transplantation. The results showed no response in patients with MDS, but 83% achieved stable disease, and the overall response rate in the JMML cohort was 75%. The study suggests that azacitidine is a safe and efficacious option for relapsed JMML.
Article
Hematology
Andrew Lin, Samantha Brown, Stephanie Chinapen, Yeon Joo Lee, Susan K. Seo, Doris M. Ponce, Zainab Shahid, Sergio Giralt, Genovefa A. Papanicolaou, Miguel-Angel Perales, Brian C. Shaffer
Summary: The reactivation of latent cytomegalovirus (CMV) is more likely to occur in recipients of allogeneic hematopoietic cell transplantation (allo-HCT) with seropositive CMV. The use of posttransplant Letermovir can effectively reduce the incidence of clinically significant CMV infection (csCMVi) in this population. However, the factors that predict csCMVi after letermovir withdrawal are not well described. This study found that hypogammaglobulinemia before letermovir discontinuation is predictive of csCMVi, while T-cell and B-cell reconstitution before letermovir withdrawal are not predictive of csCMVi. Strategies to boost CMV-specific adaptive immunity in patients with persistent hypogammaglobulinemia may help reduce csCMVi after letermovir withdrawal.
Article
Biophysics
Alexandros Spyridonidis, Myriam Labopin, Tobias Gedde-Dahl, Arnold Ganser, Matthias Stelljes, Charles Craddock, Eva Maria Wagner-Drouet, Jurjen Versluis, Thomas Schroeder, Igor Wolfgang Blau, Gerald. G. Wulf, Peter Dreger, Gitte Olesen, Henrik Sengeloev, Nicolaus Kroger, Victoria Potter, Edouard Forcade, Jakob Passweg, Regis Peffault de Latour, Johan Maertens, Keith M. O. Wilson, Jean Henri Bourhis, Juergen Finke, Eolia Brissot, Ali Bazarbachi, Sebastian Giebel, Bipin P. Savani, Arnon Nagler, Fabio Ciceri, Mohamad Mohty
Summary: This study confirms the effectiveness of the recently developed transplant conditioning intensity (TCI) score in predicting mortality and relapse rates in hematopoietic cell transplantation.
BONE MARROW TRANSPLANTATION
(2023)