Article
Medicine, Research & Experimental
Erika S. Varady, L. Angel Ayala, Pauline U. Nguyen, Vanessa M. Scarfone, Alborz Karimzadeh, Cuiwen Zhou, Xiyu Chen, Scott A. Greilach, Craig M. Walsh, Matthew A. Inlay
Summary: Donor cell conditioning with the glucocorticoid fluticasone propionate (FLU) prior to transplantation increases HSC engraftment and reduces the severity and incidence of graft-versus-host disease (GvHD) in allogeneic hosts.
EMBO MOLECULAR MEDICINE
(2023)
Review
Cell Biology
Konradin F. Muskens, Caroline A. Lindemans, Mirjam E. Belderbos
Summary: GvHD is a major complication of HCT, causing severe hematopoietic dysfunction. Immune activation during GvHD damages hematopoietic stem cells and their niche in the bone marrow, leading to reduced functionality. Complications and treatments associated with HCT exacerbate hematopoietic dysfunction.
Article
Immunology
Thomas Krueger, Rebekka Wehner, Maik Herbig, Martin Kraeter, Michael Kramer, Jan Moritz Middeke, Friedrich Stoelzel, Catrin List, Katharina Egger-Heidrich, Raphael Teipel, Uta Oelschlaegel, Martin Wermke, Helena Jambor, Manja Wobus, Johannes Schetelig, Korinna Joehrens, Torsten Tonn, Julien Subburayalu, Marc Schmitz, Martin Bornhauser, Malte von Bonin
Summary: Functional impairment of the bone marrow niche, particularly a decrease in mesenchymal stromal cells (MSCs), is associated with cytopenia and graft failure after hematopoietic cell transplantation. Acute graft-versus-host disease (aGvHD) is shown to significantly reduce MSC numbers, and this reduction can be observed before clinical onset of aGvHD. The different phenotypic and functional characteristics of MSCs depending on the occurrence of aGvHD suggest that they may contribute to alloreactivity after transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Ana Claudia Scaraficci, Patricia Maria Fernandes, Fabio Abreu Alves, Jayr Schmidt Filho, Graziella Chagas Jaguar
Summary: The study revealed that the mean time for oral GVHD to develop after AHCT was 229 days, with pain and xerostomia being the main symptoms, and ulcers being the most common oral manifestation. Patients who received myeloablative conditioning regimen had a higher survival rate.
SUPPORTIVE CARE IN CANCER
(2022)
Article
Immunology
Lydia Verlaat, Katarina Riesner, Martina Kalupa, Beate Jung, Sarah Mertlitz, Constanze Schwarz, Joerg Mengwasser, Claudine Fricke, Olaf Penack
Summary: Despite progress in allo-HCT, cGvHD remains a major hurdle, and improved pre-clinical models are needed. We developed two murine cGvHD models that resemble the clinical manifestations of cGvHD in patients. These models exhibited diverse signs of cGvHD in target organs and decelerated immune cell reconstitution. They can provide a deeper understanding of cGvHD pathology and facilitate the translation of experimental findings into human allo-HCT.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Sook-Kyoung Heo, Eui-Kyu Noh, Yoo Jin Lee, Yerang Shin, Youjin Kim, Hyeon-Su Im, Hyeyeong Kim, Su Jin Koh, Young Joo Min, Jae-Cheol Jo, Yunsuk Choi
Summary: This study investigated the serum protein profiles of patients who had undergone hematopoietic cell transplantation (HCT) to identify predictive biomarkers of severe acute graft versus host disease (GVHD). The results showed that higher levels of sVCAM-1 at baseline and on day + 14 could be significant predictive biomarkers of severe aGVHD.
Article
Medicine, General & Internal
Eun Sil Kim, Yiyoung Kwon, Yon Ho Choe, Mi Jin Kim, Keon Hee Yoo
Summary: This study investigated the outcomes of gastrointestinal graft-versus-host disease (GVHD) in pediatric patients undergoing hematopoietic stem cell transplantation (HCT) according to the clinical, endoscopic, and histologic severity. The results showed that patients with higher histologic severity had earlier onset of GVHD symptoms and a higher proportion of severe clinical gastrointestinal GVHD. It highlights the importance of histologic evaluation in the diagnosis of clinical gastrointestinal GVHD.
FRONTIERS IN MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jaspar Kloehn, Anne Kruchen, Kerstin Schuetze, Katharina Wustrau, Johanna Schrum, Ingo Mueller
Summary: Two pediatric patients underwent stem cell re-transplantation successfully, providing a new therapeutic option for steroid-refractory chronic graft-versus-host disease (SR-cGvHD).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Motoko Koyama, Geoffrey R. Hill
Summary: Allogeneic stem cell transplantation is an effective therapy for hematopoietic malignancies, relying on donor T cells and NK cells for the graft-versus-leukemia effect. However, graft-versus-host disease remains a major complication, highlighting the importance of understanding alloantigen presentation to separate beneficial effects from detrimental ones. Mouse models and tools play a key role in quantifying alloantigen presentation post-alloSCT.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mehrdad Hefazi, Sara Bolivar-Wagers, Bruce R. Blazar
Summary: This review provides the latest preclinical and clinical data on Treg cell therapy in the context of GVHD, highlighting the importance of T cell therapy in preventing and treating GVHD, and discussing future research directions and challenges.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Ashley M. Nelson, Alexandra A. Erdmann, Christopher L. Coe, Mark B. Juckett, Keayra Morris, Jennifer M. Knight, Peiman Hematti, Erin S. Costanzo
Summary: Increased synthesis and release of inflammatory signalling proteins are common among individuals with hematologic malignancies undergoing hematopoietic cell transplantation (HCT). This study examined the relationship between markers of inflammatory activity and depression symptoms following HCT. The results showed that patients with elevated levels of IL-6 and IL-10 reported more severe depression symptoms post-HCT, especially in terms of neurovegetative symptoms.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Surgery
Cecile Chague, Thomas Gautier, Ludivine Dal Zuffo, Jean-Paul Pais de Barros, Audrey Wetzel, Georges Tarris, Gaetan Pallot, Laurent Martin, Severine Valmary-Degano, Valerie Deckert, Laurent Lagrost, Etienne Daguindau, Philippe Saas
Summary: This study found that HDL deficiency leads to LPS accumulation and exacerbates aGVHD. However, administration of HDL isolated from human plasma significantly decreases the mortality and severity of aGVHD. HDL infusion also plays an important role in mitigating liver aGVHD by reducing immune infiltration and inflammation.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Oncology
Delaney Wolfe, Qiuhong Zhao, Emma Siegel, Marcin Puto, Danielle Murphy, Julianna Roddy, Yvonne Efebera, Justin Tossey
Summary: Patients with GVHD who received letermovir prophylaxis had significantly fewer CMV infections, reduced non-relapsed mortality, and improved overall survival, suggesting that letermovir prophylaxis improves outcomes in this high-risk population.
Review
Biochemistry & Molecular Biology
Jinjin Zhu, Jia Chen
Summary: HSCT is a potentially curative therapy for malignant hematologic disorders. Immune checkpoint-targeted agents can modulate immune responses and maintain immune homeostasis, reducing the risk of organ toxicity and immunosuppression associated with conventional therapy. There is an increasing number of literature reporting the application of immune checkpoint-targeted agents in HSCT settings.
MOLECULAR BIOLOGY REPORTS
(2023)
Review
Hematology
Xiaoyin Bu, Jinman Zhong, Weiru Li, Shengchun Cai, Ya Gao, Baohong Ping
Summary: Allo-HSCT is a potential curative strategy for hematological malignancies, but GVHD remains a serious complication. HLA-G, as a non-classical MHC class I molecule, plays a key role in immune tolerance and regulation of GVHD. It can serve as a predictor and therapeutic target for GVHD.
ANNALS OF HEMATOLOGY
(2021)
Article
Hematology
Nico Gagelmann, Gerald Georg Wulf, Johannes Duell, Bertram Glass, Pearl van Heteren, Bastian von Tresckow, Monika Fischer, Olaf Penack, Francis Ayuk, Herrmann Einsele, Udo Holtick, Julia Thomson, Peter Dreger, Nicolaus Kroeger
Summary: Hematotoxicity after CAR-T therapy can be managed with hematopoietic stem cell boost (HSCB), which showed a quick response and improved outcomes for sustained moderate to severe neutropenia. 31 patients received HSCB, with an overall neutrophil response rate of 84% and a median response time of 9 days. Patients with shorter duration of neutropenia had significantly better survival outcomes compared to those with longer duration. The 1-year overall survival rate was 59%.
Letter
Biophysics
Ivan Moiseev, Pascale Ambron, Manuela Badoglio, Christophe Peczynski, Grzegorz Basak, Christian Koenecke, Helene Schoemans, Olaf Penack, Zinaida Peric
BONE MARROW TRANSPLANTATION
(2023)
Letter
Biophysics
Agnieszka Piekarska, Anna Czyz, Christophe Peczynski, Pascale Ambron, Emmanuelle Polge, Ivan Moiseev, Helene Schoemans, Olaf Penack, Zinaida Peric, Grzegorz W. Basak
BONE MARROW TRANSPLANTATION
(2023)
Article
Immunology
Lydia Verlaat, Katarina Riesner, Martina Kalupa, Beate Jung, Sarah Mertlitz, Constanze Schwarz, Joerg Mengwasser, Claudine Fricke, Olaf Penack
Summary: Despite progress in allo-HCT, cGvHD remains a major hurdle, and improved pre-clinical models are needed. We developed two murine cGvHD models that resemble the clinical manifestations of cGvHD in patients. These models exhibited diverse signs of cGvHD in target organs and decelerated immune cell reconstitution. They can provide a deeper understanding of cGvHD pathology and facilitate the translation of experimental findings into human allo-HCT.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Peter Bader, Claudia Rossig, Martin Hutter, Francis Ayuketang Ayuk, Claudia D. Baldus, Veit L. Buecklein, Halvard Bonig, Gunnar Cario, Hermann Einsele, Udo Holtick, Christian Koenecke, Shahrzad Bakhtiar, Annette Kuenkele, Roland Meisel, Fabian Mueller, Ingo Mueller, Olaf Penack, Eva Rettinger, Martin G. Sauer, Paul -Gerhardt Schlegel, Jan Soerensen, Arend von Stackelberg, Brigitte Strahm, Julia Hauer, Tobias Feuchtinger, Andrea Jarisch
Summary: This retrospective study investigated the efficacy of Tisa-cel in 81 patients with pB-ALL. The results showed that CAR T cell therapy can effectively alleviate the disease, with a 2-year survival rate of 45.3%. Importantly, patients who relapsed after 6 months post-allo-HSCT had a higher survival rate, which provides valuable information for clinical decision-making.
Article
Oncology
Nneoma Adaku, Benjamin N. Ostendorf, Wenbin Mei, Sohail F. Tavazoie
Summary: The APOE genetic variants have differential modulatory effects on melanoma growth and metastasis, with the APOE2 variant enhancing melanoma progression. The low-density lipoprotein receptor-related protein 1 (LRP1) receptor mediates the cell intrinsic effects of APOE variants on melanoma progression, with protein synthesis being one of the regulated processes.
Article
Oncology
Nicola Giesen, Elena Busch, Enrico Schalk, Gernot Beutel, Maria M. Ruethrich, Marcus Hentrich, Bernd Hertenstein, Hans H. Hirsch, Meinolf Karthaus, Yascha Khodamoradi, Philipp Koehler, William Kruger, Michael Koldehoff, Robert Krause, Sibylle C. Mellinghoff, Olaf Penack, Michael Sandherr, Ruth SeggeWiss-Bernhardt, Karsten Spiekermanny, Rosanne Sprute, Jannik Stemler, Florian Weissinger, Bernhard Woermann, Hans-Heinrich Wolf, Oliver A. Cornely, Christina T. Rieger, Marie von Lilienfeld-Toal
Summary: The novel coronavirus SARS-CoV-2 and associated infectious disease COVID-19 present a significant challenge to healthcare systems worldwide, with cancer patients being identified as a high-risk population. The rapid development of vaccines and therapeutic agents against COVID-19 offers new options for improving care and protection of cancer patients. However, ongoing epidemiological changes and the emergence of new virus variants require constant revisions and adaptations of prophylaxis and treatment strategies to address these new challenges.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Infectious Diseases
Jannik Stemler, Sibylle C. Mellinghoff, Yascha Khodamoradi, Rosanne Sprute, Annika Y. Classen, Sonja E. Zapke, Martin Hoenigl, Robert Krause, Martin Schmidt-Hieber, Werner J. Heinz, Michael Klein, Philipp Koehler, Blasius Liss, Michael Koldehoff, Christoph Buhl, Olaf Penack, Georg Maschmeyer, Enrico Schalk, Cornelia Lass-Floerl, Meinolf Karthaus, Markus Ruhnke, Oliver A. Cornely, Daniel Teschner
Summary: Patients with haematological malignancies are at high risk of invasive fungal disease. The German Society of Haematology and Medical Oncology has updated their antifungal prophylaxis recommendations, recommending continued antifungal prophylaxis for patients with long-lasting neutropenia and posaconazole as the drug of choice. There is insufficient data to give general recommendations for antifungal prophylaxis in patients receiving novel treatments for HM, such as CAR-T-cell therapy or novel targeted therapies for AML.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Cell Biology
Julia Martinez-Sanchez, Marta Palomo, Alexandra Pedraza, Ana Belen Moreno-Castano, Sergi Torramade-Moix, Montserrat Rovira, Maria Queralt Salas, Joan Cid, Gines Escolar, Olaf Penack, Enric Carreras, Maribel Diaz-Ricart
Summary: This study compared the endothelial proteomic profiles in response to serum from steroid-refractory acute GVHD (SR-aGVHD) and steroid-sensitive acute GVHD (SS-aGVHD) patients. The differentially expressed proteins were mainly associated with oxidative phosphorylation, inflammation and angiogenesis, cell survival, and oxidative stress. These findings provide insights into the mechanisms of response to steroids and may serve as potential biomarkers for steroid-treatment response in SR-aGVHD patients.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Oncology
Jiaqi Fan, Anne Adams, Noelle Sieg, Jan-Michel Heger, Philipp Godel, Nadine Kutsch, David Kaul, Marcel Teichert, Bastian von Tresckow, Veit Bucklein, Gretha Goesmann, Minglun Li, Nathalie Struve, Maike Trommer, Philipp Linde, Johannes Rosenbrock, Eren Celik, Olaf Penack, Martin Stuschke, Marion Subklewe, Claus Belka, Michael von Bergwelt-Baildon, Peter Borchmann, Simone Marnitz, Christian Baues
Summary: A multicentric retrospective analysis showed that radiotherapy (RT) before CAR T-cell therapy can improve the treatment response and prognosis of DLBCL patients. Patients with localized relapses benefit more from salvage RT. Further research is needed to understand the synergistic effects between CAR T-cells and RT.
RADIOTHERAPY AND ONCOLOGY
(2023)
Article
Immunology
Marie Luise Huetter-Kroenke, Adela Neagoie, Igor Wolfgang Blau, Verena Wais, Lam Vuong, Andrea Gantner, Johann Ahn, Olaf Penack, Jacqueline Schnell, Klaus Axel Nogai, Bettina Eberspaecher, Maral Saadati, Axel Benner, Lars Bullinger, Hartmut Doehner, Donald Bunjes, Elisa Sala
Summary: The study analyzed the immune response to COVID-19 vaccination in patients after allogeneic stem cell transplantation. Results showed that 72% of patients developed a humoral response after two doses of vaccination. Additionally, booster vaccination with a third dose resulted in a seroconversion in 57% of initially non-responding patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Benedikt Obermayer, Luisa Keilholz, Thomas Conrad, Marco Frentsch, Igor-Wolfgang Blau, Lam Vuong, Stella Lesch, Kamran Movasshagi, Carola Tietze-Stolley, Lucie Loyal, Larissa Henze, Olaf Penack, Ulrik Stervbo, Nina Babel, Simon Haas, Dieter Beule, Lars Bullinger, Friedrich Wittenbecher, Il-Kang Na
Summary: The fate of individual donor T-cells is crucial for the balance between intended and adverse effects in allogeneic hematopoietic stem cell transplantation (alloHSCT). In this study, we tracked alpha beta T-cell clonotypes during stem cell mobilization and immune reconstitution after transplant. We found over 250 alpha beta T-cell clonotypes that consisted mainly of CD8(+) effector memory T cells. These clonotypes showed a distinct transcriptional signature and enhanced effector and cytotoxic functions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Olaf Penack, Christophe Peczynski, Christian Koenecke, Emmanuelle Polge, Andrea Kuhnl, Nathalie Fegueux, Michael Daskalakis, Nicolaus Kroeger, Peter Dreger, Caroline Besley, Urs Schanz, Adrian Bloor, Arnold Ganser, Edouard Forcade, Lucia Lopez Corral, Jakob R. Passweg, Urban Novak, Ivan Moiseev, Helene Schoemans, Grzegorz W. Basak, Christian Chabannon, Anna Sureda, Dina Averbuch, Bertram Glass, Rafael de la Camara, Zinaida Peric
Summary: This study examines the incidence and outcome of severe cytopenia associated with anti-CD19 CAR-T cell therapy in adult patients with large B-cell lymphoma. The cumulative incidence of grade 3 or higher cytopenia at 30 days and 100 days after CAR-T cell infusion was 9.0% and 12.1% respectively. Severe cytopenia had no significant impact on overall survival but was associated with poorer progression-free survival and higher relapse incidence. Factors such as year of CAR-T infusion and number of previous treatment lines were significantly associated with the incidence of cytopenia.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Ana Belen Moreno-Castano, Sara Fernandez, Helena Ventosa, Marta Palomo, Julia Martinez-Sanchez, Alex Ramos, Valentin Ortiz-Maldonado, Julio Delgado, Carlos Fernandez de Larrea, Alvaro Urbano-Ispizua, Olaf Penack, J. M. Nicolas, Adrian Tellez, Gines Escolar, Enric Carreras, Francesc Fernandez-Aviles, Pedro Castro, Maribel Diaz-Ricart
Summary: CAR-T cell-based immunotherapy for hematological malignancies may lead to cytokine release and immune effector cell-associated neurotoxicity syndromes. This study found that markers of endothelial dysfunction, innate immunity activation, and hemostatic imbalance could potentially be used as laboratory tools for predicting and differentiating toxicities, as well as determining their severity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Hematology
Veit Buecklein, Ariel Perez, Kai Rejeski, Gloria Iacoboni, Vindi Jurinovic, Udo Holtick, Olaf Penack, Soraya Kharboutli, Viktoria Blumenberg, Josephine Ackermann, Lisa Froelich, Grace Johnson, Kedar Patel, Brian Arciola, Rahul Mhaskar, Anthony Wood, Christian Schmidt, Omar Albanyan, Philipp Goedel, Eva Hoster, Lars Bullinger, Andreas Mackensen, Frederick Locke, Michael Von Bergwelt, Pere Barba, Marion Subklewe, Michael D. Jain
Summary: Real-world evidence shows that patients receiving CD19 chimeric antigen receptor (CAR) T-cell therapy in Europe and with tisagenlecleucel have lower survival rates. The reasons for these discrepancies, including logistic and patient-and disease-related factors, are not well understood.
