Article
Hematology
Jeffrey J. Bednarski, Clare Zimmerman, Melissa M. Berrien-Elliott, Jennifer A. Foltz, Michelle Becker-Hapak, Carly C. Neal, Mark Foster, Timothy Schappe, Ethan McClain, Patrick P. Pence, Sweta Desai, Samantha Kersting-Schadek, Pamela Wong, David A. Russler-Germain, Bryan Fisk, Wen-Rong Lie, Jeremy Eisele, Stephanie Hyde, Sima T. Bhatt, Obi L. Griffith, Malachi Griffith, Allegra A. Petti, Amanda F. Cashen, Todd A. Fehniger
Summary: In this study, memory-like NK cells (ML NK cells) were used to treat relapsed pediatric and young adult patients with AML after HCT. The results showed that ML NK cells can persist and exhibit potent anti-leukemic activity in a compatible post-HCT immune environment. The combination of DLI and ML NK cells provides a novel immunotherapy platform for relapsed AML.
Review
Hematology
Waseem Qasim
Summary: Genome editing technologies, such as CRISPR/Cas9, are being used to overcome the challenges of allogeneic T-cell therapy for blood malignancies by disrupting TCR alpha beta and preventing graft-versus-host disease. Premanufactured banks of allogeneic donor-derived CAR T cells could help address the complex logistics and high costs of autologous therapies, if HLA-mismatched T-cell therapy can be successfully addressed. Clinical trials will be crucial in determining the safety and efficacy of these modified T-cell therapies.
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
Hematology
Vincent T. Ho, Haesook T. Kim, Jennifer Brock, Ilene Galinsky, Heather Daley, Carol Reynolds, Augustine Weber, Olga Pozdnyakova, Mariano Severgnini, Sarah Nikiforow, Corey Cutler, John Koreth, Edwin P. Alyea, Joseph H. Antin, Mahasweta Gooptu, Rizwan Romee, Roman Shapiro, Yi-Bin Chen, Jacalyn Rosenblatt, David Avigan, F. Stephen Hodi, Glenn Dranoff, Catherine J. Wu, Jerome Ritz, Robert J. Soiffer
Summary: This study examined the use of GVAX vaccine after allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome/acute myeloid leukemia. Results showed that GVAX did not improve survival rates. The vaccine did not affect the reconstitution of immune cells nor showed significant differences in immune biomarkers compared to placebo.
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.
Article
Immunology
Corinna La Rosa, Flavia Chiuppesi, Yoonsuh Park, Qiao Zhou, Dongyun Yang, Ketevan Gendzekhadze, Minh Ly, Jing Li, Teodora Kaltcheva, Sandra Ortega Francisco, Miguel-Angel Gutierrez, Haris Ali, Salman Otoukesh, Idoroenyi Amanam, Amandeep Salhotra, Vinod A. Pullarkat, Ibrahim Aldoss, Michael Rosenzweig, Ahmed M. Aribi, Anthony S. Stein, Guido Marcucci, Sanjeet Singh Dadwal, Ryotaro Nakamura, Stephen J. J. Forman, Monzr M. M. Al Malki, Don J. J. Diamond
Summary: In the post-pandemic era, allogeneic hematopoietic stem cell transplant (HCT) recipients are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to reduced vaccine effectiveness caused by immunosuppressive therapy. Understanding the transfer of SARS-CoV-2 adaptive immunity from immune donors to HCT recipients can help in identifying optimal vaccination strategies for protection against evolving SARS-CoV-2 variants. A prospective observational study was conducted to analyze the immune responses in HCT recipients through T-cell replete graft. It was found that donor-derived SARS-CoV-2 T-cell responses are functional in immunosuppressed recipients and may play a critical role in post-HCT vaccine response and protection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Curtis Marcoux, David Marin, Jeremy Ramdial, Gheath AlAtrash, Amin M. Alousi, Betul Oran, Partow Kebriaei, Uday R. Popat, Katayoun Rezvani, Richard E. Champlin, Elizabeth J. Shpall, Rohtesh S. Mehta
Summary: Optimal donor selection is crucial in allogeneic hematopoietic cell transplantation, and this study compares the outcomes of patients who received transplants from younger haploidentical donors or older matched unrelated donors. The use of younger haploidentical donors was associated with improved survival and lower rates of GVHD compared to older MUDs. These findings support the use of younger haploidentical donors with post-transplant cyclophosphamide in patients with MDS or AML.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
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)
Article
Oncology
David Levitz, Yogen Saunthararajah, Kateryna Fedorov, Lauren C. Shapiro, Ioannis Mantzaris, Aditi Shastri, Noah Kornblum, R. Alejandro Sica, Nishi Shah, Marina Konopleva, Kira Gritsman, Ira Braunschweig, Dennis L. Cooper, Kith Pradhan, Amit Verma, Eric J. Feldman, Mendel Gold Finger
Summary: The once-weekly dosing regimen of LDDec and VEN in AML and MDS patients shows promising activity, with high response rates and extended time on therapy compared to standard dosing HMA/VEN regimens, highlighting the importance of noncytotoxic DNA methyltransferase 1-targeting.
CLINICAL CANCER RESEARCH
(2023)
Article
Hematology
Neal Shah, Kevin Rakszawski, Myles Nickolich, Christopher Ehmann, Baldeep Wirk, Seema Naik, Witold Rybka, Hong Zheng, Joseph Mierski, Brooke Silar, Gina Mackey, Robert Greiner, Valerie Brown, David Claxton, Shin Mineishi, Kentaro Minagawa
Summary: This study evaluated the outcomes of AML relapse after alloSCT and found that H + CT could improve the 1-year overall survival rate of patients, especially for those with a post-alloSCT relapse duration of less than 6 months.
ANNALS OF HEMATOLOGY
(2021)
Article
Immunology
Julien Subburayalu, Sebastian Dolff, Shilei Xu, Ming Sun, Monika Lindemann, Andreas Heinold, Falko M. Heinemann, Jan Willem Cohen Tervaert, Ute Eisenberger, Johannes Korth, Alexandra Brinkhoff, Andreas Kribben, Oliver Witzke, Benjamin Wilde
Summary: TFH cells and TFR cells play important roles in the formation of dnDSA after renal transplant. Activation of TFH cells is associated with the development of dnDSA, while TFR cells have an inhibitory effect on TFH cells.
CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Fatih M. Uckun, Justin Watts, Alice S. Mims, Prapti Patel, Eunice Wang, Paul J. Shami, Elizabeth Cull, Cynthia Lee, Christopher R. Cogle, Tara L. Lin
Summary: The study evaluated the risk, characteristics, and biomarkers of cytokine release syndrome (CRS) in patients receiving APVO436 for relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome. CRS incidence was not influenced by dose level, gender, race, obesity, or hematologic parameters, but age may play a role in CRS development.
Article
Cell Biology
Hemn Mohammadpour, Takemasa Tsuji, Cameron R. MacDonald, Joseph L. Sarow, Hanna Rosenheck, Saeed Daneshmandi, Jingxin Qiu, Jee Eun Choi, Junko Matsuzaki, Agnieszka K. Witkiewicz, Kristopher Attwood, Bruce R. Blazar, Kunle Odunsi, Elizabeth A. Repasky, Philip L. McCarthy
Summary: Activated donor T cells express galectin-3 (Gal-3) after allo-HCT, which suppresses T cell activation and effector cytokine secretion, leading to decreased inflammation in murine aGvHD. Gal-3 overexpression in human T cells also suppresses cytotoxic T cells and prevents severe disease in xenogeneic aGvHD models.
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.
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.
Letter
Hematology
Samer Al Hadidi, Rammurti T. Kamble, George Carrum, Helen E. Heslop, Carlos Almeida Ramos
Editorial Material
Hematology
LaQuisa C. Hill, Premal D. Lulla
Summary: The studies by Liebers et al and Enssle et al address the lack of knowledge regarding vaccine-induced T-cell immune responses in patients with lymphoma or myeloma who have depleted B-cell immunity.
Article
Biophysics
Brian D. Friend, Ibrahim N. Muhsen, Shreeya Patel, LaQuisa C. Hill, Premal Lulla, Carlos A. Ramos, S. Ravi Pingali, Rammurti T. Kamble, Tami D. John, Baheyeldin Salem, Saleh Bhar, Erin E. Doherty, John Craddock, Ghadir Sasa, Mengfen Wu, Tao Wang, Caridad Martinez, Robert A. Krance, Helen E. Heslop, George Carrum
Summary: Adding rituximab to BEAM conditioning reduces the risk of relapse in patients with relapsed/refractory HL post-transplant, leading to excellent outcomes.
BONE MARROW TRANSPLANTATION
(2022)
Review
Immunology
Wingchi K. Leung, Adanma Ayanambakkam, Helen E. Heslop, LaQuisa C. Hill
Summary: The adoptive transfer of CD19-specific CAR-T cells has significantly improved the treatment outcomes for relapsed/refractory CD19 B-cell malignancies. However, the loss of CD19 antigen limits the applicability of CAR-T cells, leading to treatment failure. This review focuses on exploring alternative targets beyond CD19 for CAR-T cell therapy.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Article
Hematology
David H. M. Steffin, Ibrahim N. Muhsen, LaQuisa C. Hill, Carlos A. Ramos, Nabil Ahmed, Meenakshi Hegde, Tao Wang, Mengfen Wu, Stephen Gottschalk, Sarah B. Whittle, Premal D. Lulla, Maksim Mamonkin, Bilal Omer, Rayne H. Rouce, Andras Heczey, Leonid S. Metelitsa, Bambi J. Grilley, Catherine Robertson, Virginia Torrano, Natalia Lapteva, Adrian P. Gee, Cliona M. Rooney, Malcolm K. Brenner, Helen E. Heslop
Summary: Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Genetically modified immune effector (IE) cells have shown benefit in hematologic malignancies and the risk for subsequent malignancy is not increased in patients treated with them, according to a retrospective review of 340 patients' data.
Review
Oncology
Leila Amini, Sara K. Silbert, Shannon L. Maude, Loretta J. Nastoupil, Carlos A. Ramos, Renier J. Brentjens, Craig S. Sauter, Nirali N. Shah, Mohamed Abou-El-Enein
Summary: Chimeric antigen receptor (CAR) T cell therapy is an effective treatment for certain hematological cancers. Successful CAR-T cell infusion requires timely preparation and consideration of various factors. This review provides a summary of the considerations in preparing patients for CAR-T cell therapy and highlights current limitations and future research areas.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Article
Biochemical Research Methods
Alireza Naghizadeh, Wei-Chung Tsao, Jong Hyun Cho, Hongye Xu, Mohab Mohamed, Dali Li, Wei Xiong, Dimitri Metaxas, Carlos A. Ramos, Dongfang Liu
Summary: Machine learning is used to process large amounts of image data in the human immune system, where immunotherapies play a crucial role in blood cancer treatment. Scientists aim to improve the efficacy of engineered immune cells expressing chimeric antigen receptors (CAR) to treat solid tumors, but face challenges in predicting and ranking the efficacy of different immune products and selecting clinical responders. Optimal cytotoxic lymphocyte function depends on the immunological synapse (IS) quality, prompting the development of a novel ML-based method to quantify CAR IS quality for potential clinical applications.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Hematology
Fateeha Furqan, Kwang W. Ahn, Yue Chen, Manmeet Kaur, Syed A. Abutalib, Nausheen Ahmed, Sairah Ahmed, Mohamed A. Kharfan-Dabaja, Johnathan Friedberg, Tara Gregory, LaQuisa Hill, Cole Sterling, Stephan K. Barta, Mazyar Shadman, Miguel-Angel Perales, Jasmine Zain, Alex F. Herrera, Craig Sauter, Mehdi Hamadani
Summary: This study evaluated the outcomes of allo-HCT in patients with relapsed/refractory ALCL and found that it can result in durable disease control in a significant proportion of patients. However, refractory disease and racial minority status predicted inferior outcomes after allo-HCT.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Norihiro Watanabe, Feiyan Mo, Rong Zheng, Royce Ma, Vanesa C. Bray, Dayenne G. van Leeuwen, Juntima Sritabal-Ramirez, Hongxiang Hu, Sha Wang, Birju Mehta, Madhuwanti Srinivasan, Lauren D. Scherer, Huimin Zhang, Sachin G. Thakkar, LaQuisa C. Hill, Helen E. Heslop, Chonghui Cheng, Malcolm K. Brenner, Maksim Mamonkin
Summary: In this study, the researchers found that the use of ibrutinib and dasatinib can fully prevent fratricide in CD7 CAR T cells, which are inhibitor drugs for key CAR/CD3z signaling kinases. The addition of ibrutinib and dasatinib rescued the ex vivo expansion of unedited CD7 CAR T cells, and these cells regained full CAR-mediated cytotoxicity both in vitro and in vivo after inhibitor withdrawal. The unedited CD7 CAR T cells persisted long term and showed sustained anti-leukemic activity in two mouse xenograft models of human T-ALL. Finally, the feasibility of manufacturing unedited autologous CD7 CAR T cells without additional engineering was demonstrated.
Article
Oncology
Thomas Pfeiffer, Ifigeneia Tzannou, Mengfen Wu, Carlos Ramos, Ghadir Sasa, Caridad Martinez, Premal Lulla, Robert A. Krance, Lauren Scherer, Daniel Ruderfer, Swati Naik, Claire Bocchini, Iain P. Fraser, Badrish Patel, Dany Ward, Tao Wang, Helen E. Heslop, Ann M. Leen, Bilal Omer
Summary: This study aimed to evaluate the feasibility and safety of posoleucel in allo-HCT recipients infected with viral infections. The results showed that posoleucel had good tolerability and achieved significant efficacy in treating multiple viral infections.
CLINICAL CANCER RESEARCH
(2023)
