Review
Cell & Tissue Engineering
Xiaoyu Zhu, Baolin Tang, Zimin Sun
Summary: Umbilical cord blood transplantation (UCBT) has been successfully used in clinics for over 30 years, offering advantages such as reliable source, ease of use, improved outcomes. Over time, UCBT has seen an increasing trend in Asia and China, while decreasing in the United States and Europe annually.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Cell & Tissue Engineering
Ying Yang, Ming Zhang, Mengqi Li, Yingchun Li, Wei Yang, Zhuogang Liu, Hongtao Wang
Summary: This study found that adding an unrelated umbilical cord blood unit to haploidentical hematopoietic stem cell transplantation can improve the prognosis and enhance the graft versus leukemia effect without increasing the incidence of graft versus host disease.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Pediatrics
Jacob Rozmus, Sima T. Bhatt, Nataliya Prokopenko Buxbaum, Geoffrey D. E. Cuvelier, Amanda M. Li, Carrie L. Kitko, Kirk R. Schultz
Summary: Hematopoietic cell transplant is an effective therapy for high risk acute lymphoblastic leukemia in pediatric patients, but graft-versus-host disease diminishes its efficacy. This review describes various interventions that aim to enhance the graft-versus-leukemia effect while limiting the harmful consequences of graft-versus-host disease.
FRONTIERS IN PEDIATRICS
(2022)
Article
Oncology
Paolo Lopedote, Elisabetta Xue, Julie Chotivatanapong, Emily C. Pao, Chiara Wychera, Ann E. Dahlberg, Laurel Thur, Laura Roberts, Kelsey Baker, Ted A. Gooley, Sangeeta Hingorani, Filippo Milano
Summary: This study aimed to identify risk factors for acute kidney injury (AKI) in cord blood transplant (CBT) patients and assess its impact on chronic kidney disease (CKD) and survival outcomes. The results showed that AKI is a frequent complication in CBT patients and is associated with worse outcomes. The mechanism of the protective role of steroids on kidney function in the setting of CBT remains unclear.
FRONTIERS IN ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Hui Li, Qi Liu, Xiaofeng Gao, Di Zhang, Shengjun Mao, Yongqian Jia
Summary: The study explored the potential of human umbilical mesenchymal stem cells transfected with IFN-γ gene and found that this treatment significantly reduced the incidence and severity of GVHD in vivo, providing a significant survival benefit.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Immunology
Linde Dekker, Evy Sanders, Caroline A. Lindemans, Coco de Koning, Stefan Nierkens
Summary: The recovery of naive T cells plays an important role in allo-HCT by functioning as both drivers and regulators in allogeneic reactions. Adequate reconstitution of naive T cells can improve GvHD prevention while maintaining GvL effects to lower relapse risk.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Yihan Ding, Chang Liu, Yiming Cai, Chang Hou, Guanghua Chen, Yang Xu, Shaoyan Hu, Depei Wu
Summary: Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have shown to be an effective treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD) with a high response rate and good survival rate.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Sara Bolivar-Wagers, Michael L. Loschi, Sujeong Jin, Govindarajan Thangavelu, Jemma H. Larson, Cameron S. McDonald-Hyman, Ethan A. Aguilar, Asim Saha, Brent H. Koehn, Mehrdad Hefazi, Mark J. Osborn, Michael C. Jensen, John E. Wagner, Christopher A. Pennell, Bruce R. Blazar
Summary: Transducing Tregs to express anti-human CD19 chimeric antigen receptor (hCAR19) can effectively reduce the incidence of graft-versus-host disease (GVHD). Additionally, hCAR19 Tregs can clear B cells and lymphoma cells, maintaining and enhancing graft-versus-tumor (GVT) responses.
Review
Pediatrics
Roisin Borrill, Kay Poulton, Robert Wynn
Summary: Allogeneic hematopoietic stem cell transplantation (HSCT) using cord blood as a source of stem cells has been proven to be an effective treatment for acute leukemia in children. Cord blood T-cells have unique immunological characteristics and have shown superior efficacy in eradicating malignancy. However, the procedure is associated with increased transplant-related mortality and morbidity.
FRONTIERS IN PEDIATRICS
(2023)
Article
Oncology
Xin-Yu Li, Li-Ping Zhan, Dian-Dian Liu, Xia-Wei Han, Han Chen, Zheng-Zhou Wu, Yin Wang, Li-Ping Que, Xiao-Jun Wu, Su Liu, Kai-Mei Wang, Shao-Liang Huang, Jian-Pei Fang, Ke Huang, Hong-Gui Xu
Summary: Using posttransplant cyclophosphamide (PTCY) as a method for controlling peri-engraftment syndrome (PES) and prophylaxis against graft-versus-host disease (GvHD) in single-unit umbilical cord blood transplantation (UCBT) for children with acute leukemia is safe and effective. Higher doses of PTCY may be more suitable for GvHD prophylaxis in UCBT patients.
Article
Oncology
Arnon Nagler, Myriam Labopin, Yener Koc, Emanuele Angelucci, Johanna Tischer, Mutlu Arat, Pietro Pioltelli, Paolo Bernasconi, Patrizia Chiusolo, J. L. Diez-Martin, Jamie Sanz, Fabio Ciceri, Zinaida Peric, Sebastian Giebel, Jonathan Canaani, Mohamad Mohty
Summary: The use of haploidentical hematopoietic cell transplantation with posttransplantation cyclophosphamide prophylaxis has shown improved outcomes in adult patients with acute lymphoblastic leukemia over time. Recent patients had significantly better leukemia-free survival and overall survival rates, with a reduced risk of nonrelapse mortality and improved OS. The 2-year OS was impressive at 75%, with a recent NRM rate of only 17%.
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)
Review
Oncology
Ying-Jun Chang, Xiang-Yu Zhao, Xiao-Jun Huang
Summary: Haploidentical stem cell transplantation is an effective alternative donor source for AML patients, with outcomes comparable to traditional transplantation methods for various types of AML. Relapse and infections post haplo-SCT remain key challenges in improving clinical outcomes for AML patients. Areas of active research include relapse prophylaxis, intervention, treatment, as well as infection prevention and therapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell & Tissue Engineering
Mike Winstead, Memphis Hill, Zarreen Amin, Mark Vander Lugt, Xiaohua Chen, Paul Szabolcs
Summary: The recovery of GDT clonality is an early part of immunological recovery after stem cell transplantation. Severe graft-versus-host disease patients have lower GDT clonality post-transplantation and show abnormal expression of gene 82. Further studies may determine if abnormal GDT spectratype can predict the clinical manifestations of graft-versus-host disease.
Article
Oncology
Kimberley Joanne Hatfield, Oystein Bruserud, Hakon Reikvam
Summary: This study found that the pretransplant lipid profiles can be used for the subclassification of patients and possibly identify those with an increased risk of death due to disease relapse or treatment toxicity. Therapeutic targeting of lipid metabolism should be further explored in these transplant recipients.
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.
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.
Article
Medicine, Research & Experimental
Jacob A. Myers, Dawn Schirm, Laura Bendzick, Rachel Hopps, Carly Selleck, Peter Hinderlie, Martin Felices, Jeffrey S. Miller
Summary: This paper investigates the mechanisms and reversal strategies of NK cell exhaustion, and proposes an in vitro model as a valuable tool for studying exhaustion regulation processes.
Article
Oncology
Martin Felices, Erin Wesley, Laura E. Bendzick, Behiye Kodal, Rachel Hopps, Bartosz Grzywacz, Peter Hinderlie, Jeffrey S. Miller, Melissa A. Geller
Summary: We investigated the effects of combined treatment with an IL15 superagonist (N-803) and immune checkpoint blockade (ICB) on immune activation in ovarian cancer patients. Our results showed that N-803 stimulated initial expansion of natural killer (NK) cells in patients, and combining ICB enhanced NK cell function. In preclinical studies, the combination of N-803 and ICB also showed improved anti-tumor control and enhanced NK cell persistence and expansion in vivo.
CANCER IMMUNOLOGY RESEARCH
(2023)
Review
Oncology
Jawad Fares, Zachary B. Davis, Julian S. Rechberger, Stephanie A. Toll, Jonathan D. Schwartz, David J. Daniels, Jeffrey S. Miller, Soumen Khatua
Summary: Despite current treatment advancements for brain tumors, including surgery, chemotherapy, and radiation, the prognosis remains poor, especially for recurrent cases. The close proximity to delicate neural structures often prevents complete surgical removal, and the toxicities of systemic therapy are a concern. However, the field of NK cell-based cancer therapy shows promise as a new avenue for treating brain tumors.
NPJ PRECISION ONCOLOGY
(2023)
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
Shernan G. Holtan, Andrea Hoeschen, Qing Cao, Celalettin Ustun, Brian C. Betts, Najla El Jurdi, Joseph Maakaron, Armin Rashidi, Jeffrey S. Miller, John E. Wagner, Bruce R. Blazar, Pamala A. Jacobson, Angela Panoskaltsis-Mortari, Daniel J. Weisdorf, Margaret L. Macmillan
Summary: Studies have shown that treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes for life-threatening acute graft-versus-host disease (aGVHD) beyond traditional immunosuppressants. Addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF) to standard aGVHD therapy has been found to be a feasible supportive care measure with potential to reduce morbidity and mortality. Further research is needed to explore the efficacy of uhCG/EGF as a complementary treatment for aGVHD.
TRANSPLANTATION AND CELLULAR THERAPY
(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)
