Review
Immunology
Guancui Yang, Xiang Wang, Shiqin Huang, Ruihao Huang, Jin Wei, Xiaoqi Wang, Xi Zhang
Summary: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for myeloid malignancies, but relapse and graft-versus-host disease (GvHD) still impact patient survival. Epigenetic agents, such as hypomethylating agents (HMAs), have been explored to reduce relapse risk and prevent GvHD, and combining epigenetic therapy with HSCT may optimize the transplantation process and prevent treatment failure.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Desiree Kunadt, Sebastian Stasik, Klaus H. Metzeler, Christoph Roellig, Christoph Schliemann, Philipp A. Greif, Karsten Spiekermann, Maja Rothenberg-Thurley, Utz Krug, Jan Braess, Alwin Kraemer, Andreas Hochhaus, Sebastian Scholl, Inken Hilgendorf, Tim H. Bruemmendorf, Edgar Jost, Bjoern Steffen, Gesine Bug, Hermann Einsele, Dennis Goerlich, Cristina Sauerland, Kerstin Schaefer-Eckart, Stefan W. Krause, Mathias Haenel, Maher Hanoun, Martin Kaufmann, Bernhard Woermann, Michael Kramer, Katja Sockel, Katharina Egger-Heidrich, Tobias Herold, Gerhard Ehninger, Andreas Burchert, Uwe Platzbecker, Wolfgang E. Berdel, Carsten Mueller-Tidow, Wolfgang Hiddemann, Hubert Serve, Matthias Stelljes, Claudia D. Baldus, Andreas Neubauer, Johannes Schetelig, Christian Thiede, Martin Bornhaeuser, Jan M. Middeke, Friedrich Stoelzel
Summary: In this study, the impact of alloHCT on AML patients with IDH1/2 mutations was investigated. It was found that certain IDH mutational subclasses, such as IDH1 R132C and IDH2 R172K, showed a significant benefit from alloHCT in terms of overall survival (OS) and relapse-free survival (RFS) compared to chemotherapy alone. AlloHCT may have prognostic value for AML risk stratification and therapeutic decision making.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Oncology
Michael Boyiadzis, Mei-Jie Zhang, Karen Chen, Hisham Abdel-Azim, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Talha Badar, Sherif M. Badawy, Minoo Battiwalla, Nelli Bejanyan, Vijaya Raj Bhatt, Valerie Brown, Paul Castillo, Jan Cerny, Edward A. Copelan, Charles Craddock, Bhagirathbhai Dholaria, Miguel Angel Diaz Perez, Christen L. Ebens, Robert Peter Gale, Siddhartha Ganguly, Lohith Gowda, Michael R. Grunwald, Shahrukh Hashmi, Gerhard C. Hildebrandt, Madiha Iqbal, Omer Jamy, Mohamed A. Kharfan-Dabaja, Nandita Khera, Hillard M. Lazarus, Richard Lin, Dipenkumar Modi, Sunita Nathan, Taiga Nishihori, Sagar S. Patel, Attaphol Pawarode, Akshay Sharma, Melhem Solh, John L. Wagner, Trent Wang, Kirsten M. Williams, Lena E. Winestone, Baldeep Wirk, Christopher S. Hourigan, Mark Litzow, Partow Kebriaei, Marcos de Lima, Kristin Page, Daniel J. Weisdorf
Summary: We investigated the impact of the number of induction/consolidation cycles on the outcomes of adult AML patients who received allo-HCT between 2008 and 2019. Our findings suggest that the number of induction cycles to complete remission (CR) has an impact on overall survival (OS) in patients who received myeloablative conditioning, with better OS observed in patients who achieved CR after 1 cycle compared to those who required 2 cycles or more. In contrast, the number of induction cycles did not affect OS in patients who received reduced-intensity conditioning. Consolidation therapy prior to allo-HCT was associated with improved OS in patients who achieved CR after 1 cycle. The presence of detectable minimal residual disease (MRD) at the time of allo-HCT did not impact outcomes in myeloablative allo-HCT, but was associated with an increased risk of relapse in reduced-intensity allo-HCT. Allo-HCT in patients with primary induction failure had significantly worse OS compared to allo-HCT in patients who achieved CR after 1-3 cycles.
Editorial Material
Hematology
Sena Kim, Jaebok Choi
Summary: This study demonstrates that the activation of TGF-beta 1 by Tregs through GARP downregulates the effector functions of NK cells in the bone marrow of AML patients with early relapse after allo-HCT, and that blocking TGF-beta 1 signaling can restore the killer instinct of human NK cells.
Review
Oncology
Rahul K. K. Nayak, Yi-Bin Chen
Summary: Allogeneic hematopoietic cell transplant is a central treatment for acute myeloid leukemia in first complete remission, but disease relapse remains a concern. Ongoing investigations are exploring maintenance therapies including targeted agents, hypomethylating agents, immunomodulatory therapies, and cellular therapies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Davidson Zhao, Mojgan Zarif, Qianghua Zhou, Jose-Mario Capo-Chichi, Andre Schuh, Mark D. Minden, Eshetu G. Atenafu, Rajat Kumar, Hong Chang
Summary: TP53 mutations are adverse-risk genetic aberrations in acute myeloid leukemia (AML). The optimal treatment approach for patients with TP53-mutated (TP53(MUT)) AML remains unclear. This study aimed to evaluate the prognostic implications of different frontline treatment strategies and transplantation for patients with TP53(MUT) AML. The results suggest that current therapeutic strategies are ineffective for TP53(MUT) AML patients, highlighting the urgent need for new treatment strategies for this high-risk population.
Article
Immunology
Jinye Zhu, Qingya Wang, Hanyun Ren, Yujun Dong, Yue Yin, Qian Wang, Zeyin Liang, Wei Liu, Qingyun Wang, Bingjie Wang, Yuan Li
Summary: This study retrospectively analyzed the effect of low-dose DAC treatment in AML/MDS patients undergoing allogeneic hematopoietic stem cell transplantation. The results showed that patients receiving DAC treatment had a significantly lower incidence of grade II-IV acute GVHD. This study provides a new treatment strategy for improving the prognosis of AML/MDS patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Xing-yu Cao, Jia-qi Chen, Hui Wang, Wei Ma, Wei-wei Liu, Fang-fang Zhang, Song Xue, Lei Dong, Ting Liu, Xiao-zhen Zhao, Chan-chan Liu, Xin Xu, Yang He, Lei Wang, Jian-ling Wang
Summary: The safety and efficacy of a myeloablative conditioning (MAC) allo-HSCT regimen containing venetoclax for high-risk AML patients were evaluated, and it was concluded that venetoclax is a feasible, safe, and effective treatment option in this patient population.
ANNALS OF MEDICINE
(2023)
Article
Biophysics
Marjan Cruijsen, Jacobien R. Hilberink, Walter J. F. M. van der Velden, Joop H. Jansen, Brigitte Bar, Nicolaas P. M. Schaap, Anton de Haan, Andre B. Mulder, Marco R. de Groot, Frederic Baron, Edo Vellenga, Nicole N. M. Blijlevens, Gerwin Huls
Summary: The combination of decitabine with a standard non-myeloablative conditioning regimen prior to allogeneic hematopoietic cell transplantation can effectively reduce relapse incidence in poor risk AML patients. The study demonstrated a one-year relapse rate of 23% and a one-year overall survival of 70% in this patient population.
BONE MARROW TRANSPLANTATION
(2021)
Article
Hematology
Marius Bill, Madlen Jentzsch, Lara Bischof, Jessica Kohlschmidt, Juliane Grimm, Laura Katharina Schmalbrock, Donata Backhaus, Dominic Brauer, Karoline Goldmann, Georg -Nikolaus Franke, Vladan Vucinic, Dietger Niederwieser, Alice S. Mims, Uwe Platzbecker, Ann-Kathrin Eisfeld, Sebastian Schwind
Summary: Somatic mutations in IDH1 and IDH2 genes are common in AML. The presence of IDH mutations may not significantly impact the prognosis of AML patients consolidated by HSCT, but specific mutation locations (IDH1 R132, IDH2 R140, and IDH2 R172) and mutation dynamics do affect the risk of relapse. IDH2 R140 mutations behave more like clonal hematopoiesis-related aberrations, while IDH1 R132 and IDH2 R172 harbor AML disease-specific features.
Article
Oncology
Katrin Teich, Michael Stadler, Razif Gabdoulline, Jyoti Kandarp, Clara Wienecke, Bennet Heida, Piroska Klement, Konstantin Buttner, Letizia Venturini, Martin Wichmann, Wolfram Puppe, Christian Schultze-Florey, Christian Koenecke, Gernot Beutel, Matthias Eder, Arnold Ganser, Michael Heuser, Felicitas Thol
Summary: Donor lymphocyte infusions (DLIs) can be used to prevent or treat relapse in acute myeloid leukemia (AML) patients after allogeneic hematopoietic cell transplantation (alloHCT). Measurable residual disease (MRD) is a valuable biomarker for predicting the response and outcome of DLI treatment. This retrospective study showed that MRD status before and after DLI treatment is prognostic for event-free survival, overall survival, cumulative incidence of relapse, and relapse-free survival.
Article
Hematology
Scott R. Solomon, Melhem Solh, Lawrence E. Morris Jr, H. Kent Holland, Lizamarie Bachier-Rodriguez, Xu Zhang, Caitlin Guzowski, Katelin C. Jackson, Stacey Brown, Asad Bashey
Summary: Pembrolizumab after autologous transplant is a safe and effective alternative postremission therapy for patients with nonfavorable risk AML who are ineligible for allogeneic transplant.
Letter
Biophysics
Emily C. Liang, Connie Chen, Rong Lu, Gabriel N. Mannis, Lori Muffly
Summary: Measurable residual disease is associated with poor prognosis in AML, and new NGS methods are highly sensitive in detecting MRD. The use of FLT3 inhibitors post-HCT is crucial for maintaining remission. Early post-HCT MRD negatively impacts PFS, while maintenance FLT3 inhibitors lead to superior PFS and OS for both MRD-negative and MRD-positive patients.
BONE MARROW TRANSPLANTATION
(2021)
Review
Oncology
Iman Abou Dalle, Ali Atoui, Ali Bazarbachi
Summary: Relapsed acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation (allo-HCT) is a challenging event, and the current treatment landscape is still facing difficulties. Recent research has allowed the development of new strategies that can improve remission rates and prolong survival.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biophysics
Alexandra M. Satty, Elizabeth Klein, Audrey Mauguen, Binni Kunvarjee, Jaap Jan Boelens, Maria Cancio, Kevin J. Curran, Nancy A. Kernan, Susan E. Prockop, Andromachi Scaradavou, Barbara Spitzer, Roni Tamari, Julianne Ruggiero, Joanne Torok-Castanza, Parinda A. Mehta, Richard J. O'Reilly, Farid Boulad
Summary: The study retrospectively evaluated the outcomes of patients with Fanconi anemia and MDS/AML who underwent allogeneic HCT with a T-cell depleted graft. The results demonstrated promising outcomes, particularly in a cohort of high-risk patients, with a high survival rate.
BONE MARROW TRANSPLANTATION
(2023)