Review
Cell & Tissue Engineering
Ying Li, Jie Hao, Zheng Hu, Yong-Guang Yang, Qi Zhou, Liguang Sun, Jun Wu
Summary: This study summarized 79 clinical trials involving the use of MSCs to prevent or treat GVHD, analyzing their characteristics and results. The researchers aimed to gain a comprehensive understanding of the progress, challenges, limitations, and future trends in the field, and provide new perspectives for the design of future trials.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Immunology
Tao Hong, Rui Wang, Xiaoqi Wang, Shijie Yang, Weihao Wang, Qiangguo Gao, Xi Zhang
Summary: Allogeneic hematopoietic stem cell transplantation is an effective therapy for hematological disorders, but acute graft-versus-host disease remains a major obstacle with potentially high mortality rates. Imbalance in intestinal microbiota is associated with the development and severity of aGVHD, impacting clinical outcomes following allo-HSCT. Monitoring and modifying the intestinal microecology post allo-HSCT may offer promising approaches for diagnosing, preventing, or treating aGVHD in clinical settings.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Fathima A. Mohamed, Govindarajan Thangavelu, Stephanie Y. Rhee, Peter T. Sage, Roddy S. O'Connor, Jeffrey C. Rathmell, Bruce R. Blazar
Summary: The therapeutic efficacy of allo-HSCT is limited by the development of GVHD, with immune dysregulation leading to expansion of alloreactive cells and reduction in regulatory cells. New therapies are needed to restore the balance between effector and regulatory immune cells while preserving the beneficial graft-versus-tumor effect.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Hematology
Noa G. Holtzman, Steven Z. Pavletic
Summary: Chronic graft-versus-host disease (cGVHD) is a systemic complication of allogeneic haematopoietic stem cell transplantation that can lead to increased morbidity and mortality. Despite limited curative treatment options, recent collaborative research efforts have led to discovery of new second-line therapies. Comprehensive and sustained multidisciplinary efforts are crucial for successful management of cGVHD.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Jiapei Liu, Zhiping Fan, Na Xu, Jieyu Ye, Yanqiu Chen, Ruoyang Shao, Yiming Sun, Qiaoyuan Wu, Qifa Liu, Hua Jin
Summary: This study evaluated the effects of ruxolitinib compared with basiliximab in the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD). The results showed that ruxolitinib had a higher overall response rate and effectively prevented chronic GVHD (cGVHD), leading to improved survival rates.
ANNALS OF HEMATOLOGY
(2023)
Article
Hematology
Jiapei Liu, Zhiping Fan, Na Xu, Jieyu Ye, Yanqiu Chen, Ruoyang Shao, Yiming Sun, Qiaoyuan Wu, Qifa Liu, Hua Jin
Summary: This study retrospectively evaluated the effects of ruxolitinib compared with basiliximab for steroid-refractory acute graft-versus-host disease (SR-aGVHD). The results showed that ruxolitinib had higher overall response and complete response rates, as well as lower incidence of chronic GVHD. Ruxolitinib also improved overall survival and failure-free survival rates. In addition, ruxolitinib significantly reduced the occurrence of EBV viremia. Therefore, ruxolitinib should be recommended for the treatment of SR-aGVHD.
ANNALS OF HEMATOLOGY
(2023)
Article
Immunology
Saurabh Kumar Gupta, Dievya Gohil, Deepshikha Dutta, Girish Ch Panigrahi, Puja Gupta, Kajal Dalvi, Twinkle Khanka, Subhash Yadav, Rajiv Kumar Kaushal, Akanksha Chichra, Sachin Punatar, Anant Gokarn, Sumeet Mirgh, Nishant Jindal, Lingaraj Nayak, Prasanth R. Tembhare, Syed Khizer Hasan, Santosh Kumar Sandur, Lal Hingorani, Navin Khattry, Vikram Gota
Summary: Researchers have found that Withaferin-A (WA), a phytomolecule obtained from Withania somnifera, has significant efficacy in preventing and treating acute graft versus host disease (aGvHD), which accounts for a significant proportion of non-relapse mortality and morbidity in patients undergoing allogeneic hematopoietic stem cell transplantation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Carina A. Baeuerlein, Musga Qureischi, Zeinab Mokhtari, Paula Tabares, Christian Brede, Ana-Laura Jordan Garrote, Simone S. Riedel, Martin Chopra, Simone Reu, Anja Mottok, Estibaliz Arellano-Viera, Carolin Graf, Miriam Kurzwart, Katharina Schmiedgen, Hermann Einsele, Matthias Woelfl, Paul-Gerhardt Schlegel, Andreas Beilhack
Summary: Research suggests that the upregulation of alpha 4 beta 7 integrin, CD162E, CD162P, and downregulation of CD62L on peripheral blood T-cells may be correlated with the development of aGvHD after allo-HCT. Other surface markers like CD25, CD69, and CC-chemokine receptors were not found to be predictive markers in this study. Based on preclinical data from mouse models, a panel of surface markers combining alpha 4 beta 7 integrin with CD62L, CD162E, and CD162P is proposed to identify patients at risk for early aGvHD after allo-HCT.
FRONTIERS IN IMMUNOLOGY
(2021)
Letter
Medicine, General & Internal
Anna R. Schreiber, Dara L. Aisner, Jonathan A. Gutman
Summary: This article reports a case of fetal-induced graft-versus-host disease, in which the mother developed fever, pancytopenia, and rash 3 weeks after the delivery of twin sons that included transfusion.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Biology
Qi Wen, Zheng-Li Xu, Yu Wang, Meng Lv, Yang Song, Zhong-Shi Lyv, Tong Xing, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang, Yuan Kong
Summary: This study found that glycolysis plays a critical role in T cell activation and induction of human aGvHD. Regulating glycolysis offers a potential pathogenesis-oriented therapeutic strategy for aGvHD patients, and the combination of GCs and glycolysis inhibitors may be a novel first-line combination therapy for aGvHD patients.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Review
Immunology
Rachel Limpert, Pan Pan, Li-Shu Wang, Xiao Chen
Summary: Allogeneic hematopoietic stem cell transplantation is a potential cure for hematologic malignancies, but graft-versus-host disease remains a major obstacle. Non-genetic factors, including nutrition, play a role in the development of GVHD. Understanding the impact of diet can help reduce the risk and manage GVHD.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Allen Cheng-Wei Li, Chen Dong, Soon-Tzeh Tay, Ashwin Ananthakrishnan, Kevin Sheng-Kai Ma
Summary: This study aimed to evaluate the safety and efficacy of vedolizumab for GI-aGVHD. The results showed that vedolizumab treatment significantly improved the overall response rate, complete response rate, and survival rate of patients with GI-aGVHD. Prophylactic use of vedolizumab did not have specific adverse events, but patients with GI-aGVHD on vedolizumab had an increased risk of infections and impaired metabolism or nutritional complications during treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Ling Qi, Jie Peng, Xianbao Huang, Ting Zhou, Genmei Tan, Fei Li
Summary: The gut microbiota is associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota reveals changes in composition and related cytokines, indicating potential avenues for prevention and treatment of aGvHD.
Review
Immunology
Makoto Murata, Takanori Teshima
Summary: This article discusses the potential of MSC therapy in the treatment of acute GVHD, along with a comparison of studies on the two products, Remestemcel-L and Temcell. While Temcell's real-world efficacy was found to be equivalent to that observed in a prospective study, the precise position of Remestemcel-L/Temcell therapy in the treatment of acute GVHD remains to be determined.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Betul Oran, Richard E. Champlin, Feng Wang, Tomoyuki Tanaka, Rima M. Saliba, Gheath Al-Atrash, Guillermo Garcia-Manero, Hagop Kantarjian, Kai Cao, Elizabeth J. Shpall, Amin M. Alousi, Rohtesh S. Mehta, Uday Popat, Andy Futreal, Koichi Takahash
Summary: The presence of clonal hematopoiesis in stem cell transplant donors for AML/MDS patients is associated with an increased risk of acute graft versus host disease. Further research is needed to investigate the mechanisms and potential interventions to improve outcomes in these cases.
Article
Hematology
Anna Hecht, Julia A. Meyer, Astrid Behnert, Eric Wong, Farid Chehab, Adam Olshen, Aaron Hechmer, Catherine Aftandilian, Rukhmi Bhat, Sung Won Choi, Satheesh Chonat, Jason E. Farrar, Mark Fluchel, Haydar Frangoul, Jennifer H. Han, Edward A. Kolb, Dennis J. Kuo, Margaret L. MacMillan, Luke Maese, Kelly W. Maloney, Aru Narendran, Benjamin Oshrine, Kirk R. Schultz, Maria L. Sulis, David Van Mater, Sarah K. Tasian, Wolf-Karsten Hofmann, Mignon L. Loh, Elliot Stieglitz
Summary: Mutations in the CBL gene can lead to various myeloid malignancies, with some pediatric patients with JMML carrying CBL mutations but having milder disease courses. The majority of CBL mutations in JMML patients are germline, not somatic mutations. The disease presentation and overall outcome of JMML patients with CBL mutations are highly diverse, and some patients have more aggressive disease with somatically acquired CBL mutations. Clinical features and methylation profiling cannot accurately distinguish patients with different types of CBL mutations, highlighting the need for germline testing.
Article
Hematology
Asim Saha, Sharon Hyzy, Tahirih Lamothe, Katelyn Hammond, Nicholas Clark, Leanne Lanieri, Prashant Bhattarai, Rahul Palchaudhuri, Geoffrey O. Gillard, Jennifer Proctor, Megan J. Riddle, Angela Panoskaltsis-Mortari, Margaret L. MacMillan, John E. Wagner, Hans-Peter Kiem, Lisa M. Olson, Bruce R. Blazar
Summary: Allo-HSCT is a potential curative treatment for blood disorders, but graft-versus-host disease (GVHD) limits its success. CD45-ADC, an antibody-drug-conjugate, facilitates stable donor cell engraftment and provides a new approach to reduce treatment toxicity.
Letter
Biophysics
Gabrielle Meyers, Mehdi Hamadani, Michael Martens, Haris Ali, Hannah Choe, Peter Dawson, Andrew C. Harris, Eric van Hooren, Willem Klaassen, Eric Leifer, Margaret L. MacMillan, Ypke van Oosterhout, Lia Perez, Iskra Pusic, Phuong Vo, John E. Levine
BONE MARROW TRANSPLANTATION
(2022)
Review
Hematology
Tewodros Mamo, Keli L. Hippen, Margaret L. MacMillan, Claudio G. Brunstein, Jeffrey S. Miller, John E. Wagner, Bruce R. Blazar, David H. McKenna
Article
Biophysics
Najla El Jurdi, Grigori Okoev, Todd E. DeFor, Shernan G. Holtan, Brian C. Betts, Bruce R. Blazar, Claudio G. Brunstein, Margaret L. MacMillan, Daniel J. Weisdorf, Mukta Arora
Summary: This study found that patients with chronic graft-versus-host disease (cGVHD) may experience flares during immunosuppressive therapy (IST), and implementing appropriate treatment measures may reduce disease progression and treatment duration.
BONE MARROW TRANSPLANTATION
(2022)
Article
Dermatology
Brittney Schultz, Daniel D. Miller, Todd DeFor, Bruce R. Blazar, Angela Panoskaltsis-Mortari, Brian C. Betts, Margaret L. MacMillan, Daniel J. Weisdorf, Shernan G. Holtan
Summary: This study found that high skin AREG immunohistochemical expression is associated with high clinical grade aGVHD, poor overall survival (OS), and increased non-relapse mortality (NRM).
JOURNAL OF CUTANEOUS PATHOLOGY
(2022)
Article
Hematology
Phuong Vo, Ted A. Gooley, Paul A. Carpenter, Mohamed L. Sorror, Margaret L. MacMillan, Todd E. DeFor, Paul J. Martin
Summary: This study examined the long-term outcomes of patients who received second-line treatment for acute GVHD after HCT. Serum albumin and total bilirubin concentrations, patient age, and the severity of abdominal pain/gut involvement were identified as important predictors of treatment outcomes. The estimated overall survival (OS) and failure-free survival (FFS) at 6 and 12 months were calculated, and predictive models for 6- and 12-month mortality were proposed.
Letter
Biophysics
Gabrielle Meyers, Mehdi Hamadani, Michael Martens, Haris Ali, Patrice Chevallier, Hannah Choe, Andrew C. Harris, Ernst Holler, Eric van Hooren, Willem Klaassen, Eric Leifer, Ypke van Oosterhout, Lia Perez, Iskra Pusic, Matthias Stelljes, Walter van der Velden, Emanuele Ammatuna, David Beauvais, Jerome Cornillon, Richard T. Maziarz, Johannes Schetelig, Jennifer Romeril, Margaret L. MacMillan, John E. Levine, Gerard Socie
BONE MARROW TRANSPLANTATION
(2023)
Article
Hematology
Nancy Gillis, Eric Padron, Tao Wang, Karen Chen, Jakob D. Devos, Stephen R. Spellman, Stephanie J. Lee, Carrie L. Kitko, Margaret L. Macmillan, Jeffrey West, Yi -Han Tang, Mingxiang Teng, Samantha Mcnulty, Todd E. Druley, Joseph A. Pidala, Aleksandr Lazaryan
Summary: Improved treatment options enable older patients to receive potentially curative allogeneic hematopoietic cell transplantation. An unintended risk associated with older donors is the transplantation of donor cells with clonal hematopoiesis, which may affect transplantation outcomes.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Hematology
Rima M. Salibaaw, Amin M. Alousia, Joseph Pidala, Mukta Arora, Stephen R. Spellman, Michael T. Hemmer, Tao Wang, Camille Abboudg, Sairah Ahmed, Joseph H. Antin, Amer Beitinjanehi, David K. Buchbinder, Michael Byrne, Jean-Yves Cahn, Hannah Choen, Rabi Hanna, Peiman HemattiP, Rammurti T. Kamble, Carrie L. Kitkor, Mary Laughlin, Lazaros Lekakis, Margaret L. MacMillan, Rodrigo Martino, Parinda A. Mehta, Taiga Nishihori, Sagar S. Patel, Miguel-Angel Perales, Hemalatha G. Rangarajan, Olov Ringden, Joseph Rosenthal, Bipin N. Savani, Kirk R. Schultz, Sachiko Seo, Takanori Teshimaag, Marjolein van der Poela, Leo F. Verdonck, Daniel Weisdorf, Baldeep Wirk, Jean A. Yared, Jeffrey Schriber, Richard E. Champlin, Stefan O. Ciurea
Summary: This retrospective registry study compared the distribution, severity, and outcomes of graft-versus-host disease (GvHD) in patients receiving haploidentical (Haplo) transplantation with post-transplantation cyclophosphamide (PTCy) prophylaxis and HLA-matched unrelated donor transplantation with conventional prophylaxis. The study found that Haplo/PTCy transplantation was associated with reduced rates of severe acute GvHD and chronic GvHD, particularly in the gastrointestinal (GI) tract.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Hematology
Catherine J. Lee, Tao Wang, Karen Chen, Mukta Arora, Ruta Brazauskas, Stephen R. Spellman, Carrie Kitko, Margaret L. MacMillan, Joseph A. Pidala, Jeffery J. Auletta, Sherif M. Badawy, Neel Bhatt, Vijaya R. Bhatt, Jean-Yves Cahn, Zachariah DeFilipp, Miguel A. Diaz, Nosha Farhadfar, Shahinaz Gadalla, Robert P. Gale, Hasan Hashem, Shahrukh Hashmi, Peiman Hematti, Sanghee Hong, Nasheed M. Hossain, Yoshihiro Inamoto, Lazaros J. Lekakis, Dipenkumar Modi, Sager Patel, Akshay Sharma, Scott Solomon, Daniel R. Couriel
Summary: Chronic graft-versus-host disease (cGVHD) is a common complication following allogeneic hematopoietic cell transplantation (HCT) in children, and it significantly affects the quality of life of long-term survivors. This study aimed to analyze the occurrence of late effects (LEs) in pediatric HCT survivors and investigate the correlation between cGVHD and subsequent neoplasms (SNs) and nonmalignant LEs (NM-LEs). The findings suggest that patients with cGVHD have a higher cumulative incidence of LEs within 10 years after HCT, and cGVHD-related features are closely associated with the occurrence of NM-LEs.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Hematology
Jo-Anne H. Young, Najla El Jurdi, Ahmad Rayes, Margaret L. MacMillan, Shernan G. Holtan, Qing Cao, Judith Witte, Mukta Arora, Daniel J. Weisdorf
Summary: This study retrospectively analyzed the infectious complications in patients with acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). The results showed that patients with steroid-sensitive GVHD had fewer bacterial and viral infections compared to patients with steroid-resistant GVHD. The study suggests that anti-infective therapy should be guided by infection density during active GVHD treatment.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Christopher J. Sipe, Mitchell G. Kluesner, Samuel P. Bingea, Walker S. Lahr, Aneesha A. Andrew, Minjing Wang, Anthony P. DeFeo, Timothy L. Hinkel, Kanut Laoharawee, John E. Wagner, Margaret L. MacMillan, Gregory M. Vercellotti, Jakub Tolar, Mark J. Osborn, R. Scott McIvor, Beau R. Webber, Branden S. Moriarity
Summary: Fanconi anemia is a rare genetic disease characterized by a lack of genes essential for DNA repair. Researchers have used digital genome editing to correct the mutated genes in patient cells, resulting in phenotypic rescue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Abdelrahman Saqr, Brooke Carlson, Christopher Staley, Armin Rashidi, Mahmoud Al-Kofahi, Thomas Kaiser, Shernan Holtan, Margaret MacMillan, Jo-Anne Young, Najla El Jurdi, Daniel Weisdorf, Alexander Khoruts, Pamala A. Jacobson
Summary: Mycophenolate mofetil (MMF) is an important immunosuppressant used after allogeneic hematopoietic cell transplantation (HCT). This study found that blood concentrations of MMF were highly variable, with low concentrations associated with the risk of graft-versus-host disease (GVHD) and high concentrations associated with toxicity. The presence of beta-glucuronidase-producing bacteria in the gastrointestinal tract may enhance the enterohepatic recirculation (EHR) of MMF, leading to higher concentrations. Individuals with high EHR had a greater abundance of certain Bacteroides species in their stool and higher exposure to MMF.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Hematology
Vijaya Raj Bhatt, Tao Wang, Karen Chen, Carrie L. Kitko, Margaret L. MacMillan, Joseph A. Pidala, Monzr M. Al Malki, Sherif M. Badawy, Amer Beitinjaneh, Siddhartha Ganguly, Betty Hamilton, Gerhard C. Hildebrandt, Lazaros J. Lekakis, Hongtao Liu, Richard T. Maziarz, Dipenkumar Modi, Hemant S. Murthy, Jaime M. Preussler, Akshay Sharma, Stephen R. Spellman, Mukta Arora, Stephanie J. Lee
Summary: In this study, the effect of chronic graft-versus-host disease (cGVHD) on nonrelapse mortality (NRM) and relapse risk was investigated in older adults undergoing allogeneic hematopoietic cell transplantation. The results revealed that cGVHD significantly increased the risk of NRM and decreased the risk of relapse, regardless of age. Older adults had a higher risk of NRM, but the impact of cGVHD on NRM did not differ based on age.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)