Review
Biochemistry & Molecular Biology
Ing S. Tiong, Sun Loo
Summary: Measurable residual disease (MRD) assessment plays an important role in prognostication and guiding treatment decisions in acute myeloid leukemia (AML). With the development of new therapeutics and the recent approval of NPM1 MRD as a regulatory endpoint, MRD-directed therapy and its potential application in clinical trials are being explored. This article reviews emerging molecular MRD markers, the impact of novel therapeutics on MRD endpoints, and the use of MRD as a predictive biomarker in guiding therapy in AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Julia-Annabell Georgi, Sebastian Stasik, Martin Bornhaeuser, Uwe Platzbecker, Christian Thiede
Summary: Allogeneic hematopoietic stem cell transplantation is the only potentially curative treatment for high-risk AML patients, but a high percentage of patients experience relapse after the transplantation. To prevent relapse, pre-emptive therapy strategies based on measurable residual disease (MRD) detection are used. Donor chimerism analysis, particularly on leukemic stem cells, has emerged as an alternative method in the post-transplant setting.
FRONTIERS IN ONCOLOGY
(2022)
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
Jacobien R. Hilberink, Linde M. Morsink, Walter J. F. M. van der Velden, Andre B. Mulder, Carin L. E. Hazenberg, Marco de Groot, Goda Choi, Jan Jacob Schuringa, Kees Meijer, Nicole M. A. Blijlevens, Emanuele Ammatuna, Gerwin Huls
Summary: The predictive value of measurable residual disease (MRD) for survival in older AML patients receiving decitabine treatment is not as significant as in patients receiving intensive chemotherapy, which indicates a different impact of MRD in these two treatment groups.
TRANSPLANTATION AND CELLULAR THERAPY
(2021)
Article
Oncology
Teresa Caballero-Velazquez, Olga Perez-Lopez, Ana Yeguas Bermejo, Eduardo Rodriguez Arboli, Enrique Colado Varela, Amparo Sempere Talens, Maria Belen Vidriales, Maria Sole-Rodriguez, Covadonga Quiros Caso, Estefania Perez Lopez, Marta Reinoso Segura, Concepcion Prats-Martin, Pau Montesinos, Jose A. Perez-Simon
Summary: This study aimed to evaluate the prognostic value of measurable residual disease (MRD) in AML patients undergoing hematopoietic stem cell transplantation (HSCT). MRD detection before and after transplantation has prognostic value, and positive MRD on day +100 after transplantation is associated with a poor prognosis. Standardized MRD testing can predict the outcome of AML patients in real life.
Article
Oncology
Jia Liu, Zhong-Xing Jiang, Xin-Sheng Xie, Ding-Ming Wan, Wei-Jie Cao, Meng Wang, Zhen-Zhen Liu, Zhen-Kun Dong, Hai-Qiong Wang, Run-Qing Lu, Yin-Yin Zhang, Qian-Qian Cheng, Ji-Xin Fan, Wei Li, Fei He, Rong Guo
Summary: The study suggests that maintenance treatment with low-dose decitabine may help reduce relapse in adult ALL patients after allo-HSCT, especially in T-ALL patients. The occurrence of GVHD is relatively low during treatment, indicating good safety profile.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Woochan Park, Ja Min Byun, Junshik Hong, Inho Kim, Dong-Yeop Shin, Seonyang Park, Youngil Koh, Sung-Soo Yoon
Summary: In this study, the efficacy and safety of G-CSF mobilized cells (G-DLI) were compared with conventionally collected DLI (C-DLI) in relapsed AML patients who received allogeneic hematopoietic stem cell transplantation. Although not statistically significant, G-DLI showed higher rates of complete remission and chimerism conversion compared to C-DLI. There was no difference in the incidence and severity of acute GVHD between the two groups. The median overall survival was similar between G-DLI and C-DLI groups.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Rui Zhang, Lili Wang, Peng Chen, Xiaoning Gao, Shuhong Wang, Fei Li, Liping Dou, Chunji Gao, Yan Li, Daihong Liu
Summary: The study demonstrated the feasibility of prophylactic DLI with/without decitabine in the early stage post-allo-HSCT in patients with unfavourable gene mutations. Significant associations were found between acute GVHD and relapse after DLI with inferior overall survival.
Article
Hematology
Alexander Pohlmann, Eva Bentgens, Christoph Schuelke, David Kuron, Christian Reicherts, Julia Marx, Linus Angenendt, Jan-Henrik Mikesch, Georg Lenz, Matthias Stelljes, Christoph Schliemann
Summary: In this study, the predictive value of spleen volume on outcome parameters and engraftment kinetics after allogeneic hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML) patients was investigated. The results showed that patients with larger spleen volume had inferior overall survival and higher cumulative incidence of non-relapse mortality (NRM) after HSCT. However, engraftment kinetics and the occurrence of graft-versus-host disease (GVHD) were not significantly different between patients with different spleen volumes.
ANNALS OF HEMATOLOGY
(2023)
Article
Hematology
Sen Li, Jiangtao Li, Ping Yang, Fei Dong, Hui Liu, Hongmei Jing
Summary: This retrospective study aimed to evaluate the efficacy and safety of PEG-rhG-CSF in lymphoma patients receiving autologous PBSCT. The results showed that compared with rhG-CSF, PEG-rhG-CSF can marginally accelerate neutrophil engraftment without increasing the risk of infectious complications and toxicity. In the PEG-rhG-CSF group, administering on day 1 can achieve faster hematologic recovery and lower infectious complications.
INDIAN JOURNAL OF HEMATOLOGY AND BLOOD TRANSFUSION
(2023)
Article
Hematology
Lauren Pommert, Eric S. Schafer, Jemily Malvar, Nathan Gossai, Ellynore Florendo, Kirthi Pulakanti, Katelyn Heimbruch, Cary Stelloh, Yueh-Yun Chi, Richard Sposto, Sridhar Rao, Van Thu Huynh, Patrick Brown, Bill H. Chang, Susan Colace, Michelle L. Hermiston, Kenneth Heym, Raymond J. Hutchinson, Joel A. Kaplan, Rajen Mody, Tracey A. O'Brien, Andrew E. Place, Peter H. Shaw, David S. Ziegler, Alan Wayne, Deepa Bhojwani, Michael J. Burke
Summary: The combination of Decitabine and Vorinostat with FLAG showed promising efficacy in treating pediatric patients with R/R AML, especially those with epigenetic alterations. The therapy was well-tolerated and effective, with a significant proportion of patients achieving complete response and MRD negativity, leading to successful hematopoietic stem cell transplant. Correlative pharmacodynamics studies also revealed the biological activity of the drugs and identified specific gene enrichment signatures in nonresponding patients.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Hematology
Midori Shima, Kagehiro Amano, Yoshiyuki Ogawa, Koichiro Yoneyama, Ryoto Ozaki, Ryota Kobayashi, Emiko Sakaida, Makoto Saito, Takashi Okamura, Toshihiro Ito, Norimichi Hattori, Satoshi Higasa, Nobuaki Suzuki, Yoshinobu Seki, Keiji Nogami
Summary: This study evaluated the efficacy, safety, and pharmacokinetics of emicizumab in patients with acquired hemophilia A. The results showed that 91.7% of patients completed emicizumab treatment without experiencing any major bleeds. There were no deaths or serious adverse events related to bleeding or infection reported.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Microbiology
Chiara Cattaneo, Francesco Marchesi, Irene Terrenato, Valentina Bonuomo, Nicola Stefano Fracchiolla, Mario Delia, Marianna Criscuolo, Anna Candoni, Lucia Prezioso, Davide Facchinelli, Crescenza Pasciolla, Maria Ilaria Del Principe, Michelina Dargenio, Caterina Buquicchio, Maria Enza Mitra, Francesca Farina, Erika Borlenghi, Gianpaolo Nadali, Vito Pier Gagliardi, Luana Fianchi, Mariarita Sciume, Pierantonio Menna, Alessandro Busca, Giuseppe Rossi, Livio Pagano
Summary: This study evaluated the incidence of invasive fungal diseases (IFD) in FLT3-mutated AML patients during chemotherapy + midostaurin induction and its correlation with different antifungal (AF) prophylaxis strategies. The results showed that the incidence of IFD was not affected by different AF strategies, and age was the only risk factor for IFD, while achieving complete remission after first induction was the only risk factor for survival.
Article
Oncology
Xu-Sheng Sun, Zhe Wang, Shu-Hua Ren, He-Lin Zhang, Li-Jun Liu, Hong-Bo Du, Xiao-Wei Liu, Jun-Feng Liu
Summary: Primary prophylactic treatment with PEG-rhG-CSF can effectively reduce the incidence of neutropenia in patients with non-small cell lung cancer (NSCLC) during multiple cycles of chemotherapy, with acceptable safety and tolerability.
Article
Dermatology
Michihiro Hide, Isao Ohsawa, Christina Nurse, Ming Yu
Summary: The safety and efficacy of lanadelumab for the prevention of HAE attacks were studied in Japanese patients. Results showed a significant reduction in HAE attack rate in patients treated with lanadelumab over a 52-week period. These findings support the use of lanadelumab as prophylactic therapy for Japanese patients with HAE, consistent with global phase 3 studies.
JOURNAL OF DERMATOLOGY
(2023)
Review
Oncology
Yimei Feng, Xiaoli Chen, Kaniel Cassady, Zhongmin Zou, Shijie Yang, Zheng Wang, Xi Zhang
Summary: mTOR inhibitors, such as Rapamycin and Rapamycin analogs, have emerged as a promising class of agents for treating malignant blood diseases. Their evolving role in the management of hematologic disease, including leukemia, lymphoma, myeloma, immune hemocytopenia, and GVHD, is supported by experimental evidence of their molecular mechanisms. These inhibitors are increasingly seen as a trusted therapeutic in the clinical hematologist's toolbelt and should be considered more routinely in combination therapy.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Xiaoli Chen, Hengrui Sun, Kaniel Cassady, Shijie Yang, Ting Chen, Li Wang, Hongju Yan, Xi Zhang, Yimei Feng
Summary: Sirolimus is effective in reducing the incidence of grade II-IV acute GVHD but does not show significant improvement in chronic GVHD, overall survival, and relapse rate. However, it may increase the risk of thrombotic microangiopathy (TMA) and veno-occlusive disease (VOD) events.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Xiaoqi Wang, Kaniel Cassady, Zhongmin Zou, Xi Zhang, Yimei Feng
Summary: The combination of PD-1 monoclonal antibody and autologous stem cell transplantation appears to be a promising regimen for treating refractory Hodgkin's lymphoma, providing a novel approach to treatment in this difficult-to-treat setting.
FRONTIERS IN MEDICINE
(2021)
Article
Medicine, Research & Experimental
Qin Wen, Li Gao, Jing-kang Xiong, Qiong Li, San-bin Wang, Ji-shi Wang, Fang Liu, Cheng Zhang, Yao Liu, Pei-yan Kong, Xian-gui Peng, Jun Rao, Lei Gao, Xi Zhang
Summary: The study demonstrates that frontline auto-HSCT can improve the prognosis of intermediate/high-risk DLBCL patients, resulting in higher overall survival and progression-free survival rates.
CURRENT MEDICAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Wei-Le Wang, Ching Ouyang, Natalie M. Graham, Yuankun Zhang, Kaniel Cassady, Estefany Y. Reyes, Min Xiong, Alicia M. Davis, Kathie Tang, Defu Zeng, Mark P. Boldin
Summary: Research has shown that the absence of miR-142 gene in T-reg cells can lead to systemic autoimmune disorders. The study also revealed that miR-142 deficiency in T-reg cells results in excessive production and signaling of interferon gamma, which can be alleviated by inhibiting interferon gamma.
Article
Immunology
Yun Zhang, Ping Wang, Kaniel Cassady, Zhongmin Zou, Yi Li, Xiaojuan Deng, Wuchen Yang, Xiangui Peng, Xi Zhang, Yimei Feng
Summary: This study aimed to investigate the prognostic role of residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) in acute myeloid leukemia (AML) patients before allogeneic hemopoietic stem cell transplantation (allo-HSCT), and to determine the impact of MRD eradication on guiding the timing of HSCT. The findings revealed that achieving MFC-MRD <10-3 significantly reduced the risk of AML relapse and improved overall survival (OS) and disease-free survival (DFS) for patients. Haplo-HSCT may be a preferred option for patients who did not achieve MRD negativity.
TRANSPLANT IMMUNOLOGY
(2022)
Article
Hematology
Xiaohui Kong, Xiwei Wu, Bixin Wang, Deye Zeng, Kaniel Cassady, Ubaydah Nasri, Moqian Zheng, Alyssa Wu, Hanjun Qin, Weimin Tsai, Amandeep Salhotra, Ryotaro Nakamura, Paul J. Martin, Defu Zeng
Summary: Expansion of CXCR5-PD-1(hi) peripheral T-helper (Tph) cells in patients with chronic graft-versus-host disease (cGVHD) is associated with disease severity. These cells promote memory B-cell differentiation and immunoglobulin G production through interleukin 21 (IL-21). Tph cells in the blood and tissue-resident T-helper (Trh) cells in cGVHD target tissues share T-cell receptor alpha and beta repertoires, and their trafficking between the blood and target tissues is controlled by IL-21R-BCL6 signaling and T-bet. The development and expansion of Tph and Trh cells are important in the pathogenesis of cGVHD.
Article
Biotechnology & Applied Microbiology
Yimei Feng, Yao Quan, Kaniel Cassady, Zhongmin Zou, Yuan Gao, Xi Zhang
Summary: This study retrospectively reported the clinical characteristics of 42 ITP patients in southwest China after COVID-19 vaccination. It found that platelet counts decreased after the first vaccine dose, but recovered significantly after treatment. The study reassures the safety of the vaccine for ITP patients, with temporary aggravation of thrombocytopenia that can be effectively controlled.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2022)
Article
Hematology
Dezhi Huang, Qiong Li, Xinlei Li, Naya Ma, Yishuo Duan, Lidan Zhu, Jiali Li, Qin Wen, Lei Gao, Cheng Yang, Lingyi Rao, Li Gao, Xi Zhang, Jun Rao
Summary: This study investigated the prognostic value of circulating tumor DNA (ctDNA) in extranodal NK/T-cell lymphoma (ENKTL). The results showed that integrating ctDNA into other prognostic models could significantly distinguish different-risk groups and predict patients' disease progression and survival. This study provides a potential basis for personalized treatment in ENKTL.
Article
Multidisciplinary Sciences
Yuankun Zhang, Qingxiao Song, Kaniel Cassady, Michael Lee, Haidong Tang, Moqian Zheng, Bixin Wang, Dustin E. Schones, Yang-Xin Fu, Arthur D. Riggs, Paul J. Martin, Ru Feng, Defu Zeng
Summary: Previous assumptions about PD-L1/CD80 interactions being trans have been challenged by recent reports, which suggest that these interactions are actually cis. Blocking PD-L1/CD80 interactions on antigen-presenting cells has been found to reduce antitumor immunity, while blocking both cis and trans interactions or just the trans interactions can enhance antitumor immunity by increasing IFN-γ-producing CD8+ T cells and IFN-γ-dependent NOS2-expressing tumor-associated macrophages. Overall, blocking PD-L1/CD80 interactions in vivo has a net positive effect on CD8+ T cell-mediated antitumor immunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Xixi Xiang, Fu Li, Sha Zhou, Yunjing Zeng, Xiaojuan Deng, Hongyang Zhang, Jiali Li, Hongyun Liu, Jun Rao, Lei Gao, Cheng Zhang, Qin Wen, Li Gao, Xi Zhang
Summary: In this study, DNA next-generation sequencing (NGS) data and clinical information from 86 CLL patients were analyzed to identify gene markers related to treatment-free survival (TFS) length. PPARA was identified as one of the critical genes within a genetic network that influences the prognosis and TFS of CLL through multiple pathogenic pathways.
Article
Hematology
Dan Wang, Kaniel Cassady, Zhongmin Zou, Xi Zhang, Yimei Feng
Summary: This study summarizes the role and potential mechanism of rapamycin in the treatment of immune thrombocytopenia (ITP). Clinical data and basic research suggest that rapamycin has efficacy in treating ITP and is well tolerated. It can regulate immune cell subsets, modulate cytokine secretion, and promote platelet autophagy.
Meeting Abstract
Oncology
Yuankun Zhang, Qingxiao Song, Michael Lee, Haidong Tang, Kaniel Cassady, Yang-Xin Fu, Dustin E. Schones, Arthur Riggs, Ru Feng, Defu Zeng
Article
Oncology
Lidan Zhu, Ping Wang, Wei Zhang, Qiong Li, Jingkang Xiong, Jiali Li, Xiaojuan Deng, Yao Liu, Chao Yang, Peiyan Kong, Xiangui Peng, Jiang F. Zhong, Jun Rao, Xi Zhang
CANCER MANAGEMENT AND RESEARCH
(2020)