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1,950 results on '"Soiffer, Robert J."'

2. Health-related quality of life with gilteritinib vs placebo posttransplant for FLT3-ITD+ acute myeloid leukemia

Author

Hamilton, Betty K., Pandya, Bhavik J., Ivanescu, Cristina, Elsouda, Dina, Hamadani, Mehdi, Chen, Yi-Bin, Levis, Mark J., Ueda Oshima, Masumi, Litzow, Mark R., Soiffer, Robert J., Ustun, Celalettin, Perl, Alexander E., Singh, Anurag K., Geller, Nancy, Hasabou, Nahla, Rosales, Matt, Cella, David, Corredoira, Laura, Pestana, Carolina, Horowitz, Mary M., and Logan, Brent

Published
2024
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3. Active infection at the time of CD34+ selected stem cell boost is associated with treatment failure and poor overall survival

Author

Shapiro, Roman M., Kim, Haesook T., Dulery, Remy, Liney, Deborah, Garrity, Heather M., Panaro, Kevin, Au, Chloe, Gervais, Casey, Little, Jessica S., Ho, Vincent T., Cutler, Corey S., Koreth, John, Gooptu, Mahasweta, Antin, Joseph H., Kelkar, Amar H., Romee, Rizwan, Wu, Catherine J., Ritz, Jerome, Soiffer, Robert J., and Nikiforow, Sarah

Published
2024
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4. Prophylactic maintenance with venetoclax/azacitidine after reduced-intensity conditioning allogeneic transplant for high-risk MDS and AML

Author

Garcia, Jacqueline S., Kim, Haesook T., Murdock, H. Moses, Ansuinelli, Michela, Brock, Jennifer, Cutler, Corey S., Gooptu, Mahasweta, Ho, Vincent T., Koreth, John, Nikiforow, Sarah, Romee, Rizwan, Shapiro, Roman, DeAngelo, Daniel J., Stone, Richard M., Bat-Erdene, Denbaa, Ryan, Jeremy, Contreras, Manuel E., Fell, Geoffrey, Letai, Anthony, Ritz, Jerome, Lindsley, R. Coleman, Soiffer, Robert J., and Antin, Joseph H.

Published
2024
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7. Distinct evolutionary paths in chronic lymphocytic leukemia during resistance to the graft-versus-leukemia effect

Author

Bachireddy, Pavan, Ennis, Christina, Nguyen, Vinhkhang N, Gohil, Satyen H, Clement, Kendell, Shukla, Sachet A, Forman, Juliet, Barkas, Nikolaos, Freeman, Samuel, Bavli, Natalie, Elagina, Liudmila, Leshchiner, Ignaty, Mohammad, Arman W, Mathewson, Nathan D, Keskin, Derin B, Rassenti, Laura Z, Kipps, Thomas J, Brown, Jennifer R, Getz, Gad, Ho, Vincent T, Gnirke, Andreas, Neuberg, Donna, Soiffer, Robert J, Ritz, Jerome, Alyea, Edwin P, Kharchenko, Peter V, and Wu, Catherine J

Subjects
Stem Cell Research, Hematology, Rare Diseases, Cancer, Stem Cell Research - Nonembryonic - Human, Lymphoma, Transplantation, Genetics, Stem Cell Research - Nonembryonic - Non-Human, Graft vs Host Disease, Graft vs Leukemia Effect, HLA Antigens, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Transplantation, Homologous, Biological Sciences, Medical and Health Sciences
Abstract

Leukemic relapse remains a major barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aggressive hematologic malignancies. The basis for relapse of advanced lymphoid malignancies remains incompletely understood and may involve escape from the graft-versus-leukemia (GvL) effect. We hypothesized that for patients with chronic lymphocytic leukemia (CLL) treated with allo-HSCT, leukemic cell-intrinsic features influence transplant outcomes by directing the evolutionary trajectories of CLL cells. Integrated genetic, transcriptomic, and epigenetic analyses of CLL cells from 10 patients revealed that the clinical kinetics of post-HSCT relapse are shaped by distinct molecular dynamics. Early relapses after allo-HSCT exhibited notable genetic stability; single CLL cell transcriptional analysis demonstrated a cellular heterogeneity that was static over time. In contrast, CLL cells relapsing late after allo-HSCT displayed notable genetic evolution and evidence of neoantigen depletion, consistent with marked single-cell transcriptional shifts that were unique to each patient. We observed a greater rate of epigenetic change for late relapses not seen in early relapses or relapses after chemotherapy alone, suggesting that the selection pressures of the GvL bottleneck are unlike those imposed by chemotherapy. No selective advantage for human leukocyte antigen (HLA) loss was observed, even when present in pretransplant subpopulations. Gain of stem cell modules was a common signature associated with leukemia relapse regardless of posttransplant relapse kinetics. These data elucidate the biological pathways that underlie GvL resistance and posttransplant relapse.

Published
2020

8. Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease

Author

Koshy, Anita G., Kim, Haesook T., Liegel, Jessica, Arnason, Jon, Ho, Vincent T., Antin, Joseph H., Joyce, Robin, Cutler, Corey, Gooptu, Mahasweta, Nikiforow, Sarah, Logan, Emma K., Elavalakanar, Pavania, Narcis, Michele, Stroopinsky, Dina, Avigan, Zachary M., Boussi, Leora, Stephenson, Susan, El Banna, Hassan, Bindal, Poorva, Cheloni, Giulia, Avigan, David E., Soiffer, Robert J., and Rosenblatt, Jacalyn

Published
2023
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10. Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

Author

Penter, Livius, Liu, Yang, Wolff, Jacquelyn O., Yang, Lin, Taing, Len, Jhaveri, Aashna, Southard, Jackson, Patel, Manishkumar, Cullen, Nicole M., Pfaff, Kathleen L., Cieri, Nicoletta, Oliveira, Giacomo, Kim-Schulze, Seunghee, Ranasinghe, Srinika, Leonard, Rebecca, Robertson, Taylor, Morgan, Elizabeth A., Chen, Helen X., Song, Minkyung H., Thurin, Magdalena, Li, Shuqiang, Rodig, Scott J., Cibulskis, Carrie, Gabriel, Stacey, Bachireddy, Pavan, Ritz, Jerome, Streicher, Howard, Neuberg, Donna S., Hodi, F. Stephen, Davids, Matthew S., Gnjatic, Sacha, Livak, Kenneth J., Altreuter, Jennifer, Michor, Franziska, Soiffer, Robert J., Garcia, Jacqueline S., and Wu, Catherine J.

Published
2023
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11. Targeting PI3Kδ function for amelioration of murine chronic graft-versus-host disease

Author

Paz, Katelyn, Flynn, Ryan, Du, Jing, Tannheimer, Stacey, Johnson, Amy J, Dong, Shuai, Stark, Anne-Katrien, Okkenhaug, Klaus, Panoskaltsis-Mortari, Angela, Sage, Peter T, Sharpe, Arlene H, Luznik, Leo, Ritz, Jerome, Soiffer, Robert J, Cutler, Corey S, Koreth, John, Antin, Joseph H, Miklos, David B, MacDonald, Kelli P, Hill, Geoffrey R, Maillard, Ivan, Serody, Jonathan S, Murphy, William J, Munn, David H, Feser, Colby, Zaiken, Michael, Vanhaesebroeck, Bart, Turka, Laurence A, Byrd, John C, and Blazar, Bruce R

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Immunology, Infectious Diseases, Rare Diseases, Transplantation, Prevention, Stem Cell Research, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Animals, B-Lymphocytes, Bone Marrow Transplantation, Bronchiolitis Obliterans, Chronic Disease, Class I Phosphatidylinositol 3-Kinases, Disease Models, Animal, Graft vs Host Disease, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Mutant Strains, Phosphoinositide-3 Kinase Inhibitors, Scleroderma, Localized, T-Lymphocytes, Helper-Inducer, basic (laboratory) research, science, graft-versus-host disease, immunobiology, immunosuppressant - other, basic (laboratory) research/science, Medical and Health Sciences, Surgery, Clinical sciences
Abstract

Chronic graft-versus-host disease (cGVHD) is a leading cause of morbidity and mortality following allotransplant. Activated donor effector T cells can differentiate into pathogenic T helper (Th)-17 cells and germinal center (GC)-promoting T follicular helper (Tfh) cells, resulting in cGVHD. Phosphoinositide-3-kinase-δ (PI3Kδ), a lipid kinase, is critical for activated T cell survival, proliferation, differentiation, and metabolism. We demonstrate PI3Kδ activity in donor T cells that become Tfh cells is required for cGVHD in a nonsclerodermatous multiorgan system disease model that includes bronchiolitis obliterans (BO), dependent upon GC B cells, Tfhs, and counterbalanced by T follicular regulatory cells, each requiring PI3Kδ signaling for function and survival. Although B cells rely on PI3Kδ pathway signaling and GC formation is disrupted resulting in a substantial decrease in Ig production, PI3Kδ kinase-dead mutant donor bone marrow-derived GC B cells still supported BO cGVHD generation. A PI3Kδ-specific inhibitor, compound GS-649443, that has superior potency to idelalisib while maintaining selectivity, reduced cGVHD in mice with active disease. In a Th1-dependent and Th17-associated scleroderma model, GS-649443 effectively treated mice with active cGVHD. These data provide a foundation for clinical trials of US Food and Drug Administration (FDA)-approved PI3Kδ inhibitors for cGVHD therapy in patients.

Published
2019

12. Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for IDH2-mutated myeloid malignancies

Author

Fathi, Amir T., Kim, Haesook T., Soiffer, Robert J., Levis, Mark J., Li, Shuli, Kim, Annette S., Mims, Alice S., DeFilipp, Zachariah, El-Jawahri, Areej, McAfee, Steven L., Brunner, Andrew M., Narayan, Rupa, Knight, Laura W., Kelley, Devon, Bottoms, AJ S., Perry, Lindsey H., Wahl, Jonathan L., Brock, Jennifer, Breton, Elayne, Ho, Vincent T., and Chen, Yi-Bin

Published
2022
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16. Impact of diagnostic genetics on remission MRD and transplantation outcomes in older patients with AML

Author

Murdock, H. Moses, Kim, Haesook T., Denlinger, Nathan, Vachhani, Pankit, Hambley, Bryan, Manning, Bryan S., Gier, Shannon, Cho, Christina, Tsai, Harrison K., McCurdy, Shannon, Ho, Vincent T., Koreth, John, Soiffer, Robert J., Ritz, Jerome, Carroll, Martin P., Vasu, Sumithira, Perales, Miguel-Angel, Wang, Eunice S., Gondek, Lukasz P., Devine, Steven, Alyea, Edwin P., III, Lindsley, R. Coleman, and Gibson, Christopher J.

Published
2022
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17. BET-bromodomain and EZH2 inhibitor–treated chronic GVHD mice have blunted germinal centers with distinct transcriptomes

Author

Zaiken, Michael C., Flynn, Ryan, Paz, Katelyn G., Rhee, Stephanie Y., Jin, Sujeong, Mohamed, Fathima A., Saha, Asim, Thangavelu, Govindarajan, Park, Paul M.C., Hemming, Matthew L., Sage, Peter T., Sharpe, Arlene H., DuPage, Michel, Bluestone, Jeffrey A., Panoskaltsis-Mortari, Angela, Cutler, Corey S., Koreth, John, Antin, Joseph H., Soiffer, Robert J., Ritz, Jerome, Luznik, Leo, Maillard, Ivan, Hill, Geoffrey R., MacDonald, Kelli P.A., Munn, David H., Serody, Jonathan S., Murphy, William J., Kean, Leslie S., Zhang, Yi, Bradner, James E., Qi, Jun, and Blazar, Bruce R.

Published
2022
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18. GM-CSF secreting leukemia cell vaccination for MDS/AML after allogeneic HSCT: a randomized, double-blinded, phase 2 trial

Author

Ho, Vincent T., Kim, Haesook T., Brock, Jennifer, Galinsky, Ilene, Daley, Heather, Reynolds, Carol, Weber, Augustine, Pozdnyakova, Olga, Severgnini, Mariano, Nikiforow, Sarah, Cutler, Corey, Koreth, John, Alyea, Edwin P., III, Antin, Joseph H., Gooptu, Mahasweta, Romee, Rizwan, Shapiro, Roman, Chen, Yi-Bin, Rosenblatt, Jacalyn, Avigan, David, Hodi, F. Stephen, Dranoff, Glenn, Wu, Catherine J., Ritz, Jerome, and Soiffer, Robert J.

Published
2022
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20. Active infection at the time of CD34+ selected stem cell boost is associated with treatment failure and poor survival

Author

Shapiro, Roman M, primary, Kim, Haesook T, additional, Dulery, Remy, additional, Liney, Deborah, additional, Garrity, Heather M, additional, Panaro, Kevin M., additional, Au, Chloe, additional, Gervais, Casey, additional, Little, Jessica S., additional, Ho, Vincent T., additional, Cutler, Corey S., additional, Koreth, John, additional, Gooptu, Mahasweta, additional, Antin, Joseph H., additional, Kelkar, Amar H., additional, Romee, Rizwan, additional, Wu, Catherine J., additional, Ritz, Jerome, additional, Soiffer, Robert J., additional, and Nikiforow, Sarah, additional

Published
2024
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21. Adding venetoclax to fludarabine/busulfan RIC transplant for high-risk MDS and AML is feasible, safe, and active

Author

Garcia, Jacqueline S., Kim, Haesook T., Murdock, H. Moses, Cutler, Corey S., Brock, Jennifer, Gooptu, Mahasweta, Ho, Vincent T., Koreth, John, Nikiforow, Sarah, Romee, Rizwan, Shapiro, Roman, Loschi, Fiona, Ryan, Jeremy, Fell, Geoffrey, Karp, Hannah Q., Lucas, Fabienne, Kim, Annette S., Potter, Danielle, Mashaka, Thelma, Stone, Richard M., DeAngelo, Daniel J., Letai, Anthony, Lindsley, R. Coleman, Soiffer, Robert J., and Antin, Joseph H.

Published
2021
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23. Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy

Author

Bachireddy, Pavan, Azizi, Elham, Burdziak, Cassandra, Nguyen, Vinhkhang N., Ennis, Christina S., Maurer, Katie, Park, Cameron Y., Choo, Zi-Ning, Li, Shuqiang, Gohil, Satyen H., Ruthen, Neil G., Ge, Zhongqi, Keskin, Derin B., Cieri, Nicoletta, Livak, Kenneth J., Kim, Haesook T., Neuberg, Donna S., Soiffer, Robert J., Ritz, Jerome, Alyea, Edwin P., Pe’er, Dana, and Wu, Catherine J.

Published
2021
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25. Health-related quality of life with gilteritinib vs placebo posttransplant for FLT3-ITD+acute myeloid leukemia

Author

Hamilton, Betty K., Pandya, Bhavik J., Ivanescu, Cristina, Elsouda, Dina, Hamadani, Mehdi, Chen, Yi-Bin, Levis, Mark J., Ueda Oshima, Masumi, Litzow, Mark R., Soiffer, Robert J., Ustun, Celalettin, Perl, Alexander E., Singh, Anurag K., Geller, Nancy, Hasabou, Nahla, Rosales, Matt, Cella, David, Corredoira, Laura, Pestana, Carolina, Horowitz, Mary M., and Logan, Brent

Abstract

•Gilteritinib maintenance therapy after allogeneic HCT in FLT3-ITDAML is not associated with any difference in HRQOL compared with placebo.•Despite a higher incidence of adverse events, gilteritinib was not associated with any patient-reported impact of side effects.

Published
2024
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28. Gilteritinib as Post-Transplant Maintenance for Acute Myeloid Leukemia With Internal Tandem Duplication Mutation of FLT3

Author

Levis, M, Hamadani, M, Logan, B, Jones, R, Singh, A, Litzow, M, Wingard, J, Papadopoulos, E, Perl, A, Soiffer, R, Ustun, C, Ueda Oshima, M, Uy, G, Waller, E, Vasu, S, Solh, M, Mishra, A, Muffly, L, Kim, H, Mikesch, J, Najima, Y, Onozawa, M, Thomson, K, Nagler, A, Wei, A, Marcucci, G, Geller, N, Hasabou, N, Delgado, D, Rosales, M, Hill, J, Gill, S, Nuthethi, R, King, D, Wittsack, H, Mendizabal, A, Devine, S, Horowitz, M, Chen, Y, Agura, E, Altman, J, Anagnostopoulos, A, Anand, S, Artz, A, Aulitzky, W, Balderman, S, Ballen, K, Becker, M, Beguin, Y, Berkahn, L, Berneman, Z, Bhatt, V, Bilmon, I, Bonifazi, F, Briggs, A, Bruno, B, Brunstein, C, Byrne, M, Byrne, J, Cabrero, M, Cairoli, R, Carrum, G, Cerny, J, Cheong, J, Ciceri, F, Colorado, M, Cook, R, Couriel, D, Craddock, C, Damon, L, Deol, A, Desbrosses, Y, Di Grazia, C, Di Stasi, A, Dias, A, Dorritie, K, Essell, J, Eto, T, Farag, S, Forcade, E, Frankfurt, O, Fujiwara, S, Fukuda, T, Fukushima, K, Furst, S, Goto, T, Hall, A, Hatta, S, Hicheri, Y, Horwitz, M, Hou, H, How, J, Howard, D, Hsu, W, Huynh, A, Irvine, D, Ishikawa, T, Jamieson, K, Jedrzejczak, W, Jethava, Y, Jimenez, A, Jung, C, Kanda, J, Karakasis, D, Kato, J, Kekre, N, Khera, N, Klein, A, Kobbe, G, Kornblit, B, Kota, V, Lachance, S, Leber, B, Lee, C, Lee, J, Lin, T, Liu, T, Martelli, M, Martinez, C, Matsuoka, K, Mccarty, J, Mendez, L, Michelis, F, Mineishi, S, Mohty, M, Moors, I, Motyckova, G, Mueller, L, Nakamae, H, Nakano, N, Nathan, S, Nicholson, E, Norkin, M, Ogawa, Y, Olesen, G, Oluwole, O, Pantin, J, Paulson, K, Pemberton, L, Perera, T, Piatkowska-Jakubas, B, Poire, X, Protheroe, R, Rambaldi, A, Ritchie, D, Ross, K, Rubio, M, Santarone, S, Sanz Caballer, J, Sawa, M, Schaar, D, Scheid, C, Schriber, J, Seropian, S, Shah, N, Shore, T, Gil, J, Sobecks, R, Socie, G, Sprague, K, Spyridonidis, A, Stelljes, M, Stiff, P, Stuart, R, Tanaka, M, Tandra, A, Tholouli, E, Thomas, X, Tiribelli, M, Tomlinson, B, Tsirigotis, P, Tzachanis, D, Uchida, N, Ueda, M, Valcarcel Ferreiras, D, Wagner, E, Watson, A, Weisdorf, D, Wolschke, C, Wrobel, T, Yakoub-Agha, I, Yamauchi, T, Yared, J, Yeh, S, Yoon, S, Yoshihara, S, Null, N, Levis, Mark J., Hamadani, Mehdi, Logan, Brent, Jones, Richard J., Singh, Anurag K., Litzow, Mark, Wingard, John R., Papadopoulos, Esperanza B., Perl, Alexander E., Soiffer, Robert J., Ustun, Celalettin, Ueda Oshima, Masumi, Uy, Geoffrey L., Waller, Edmund K., Vasu, Sumithra, Solh, Melhem, Mishra, Asmita, Muffly, Lori, Kim, Hee-Je, Mikesch, Jan-Henrik, Najima, Yuho, Onozawa, Masahiro, Thomson, Kirsty, Nagler, Arnon, Wei, Andrew H., Marcucci, Guido, Geller, Nancy L., Hasabou, Nahla, Delgado, David, Rosales, Matt, Hill, Jason, Gill, Stanley C., Nuthethi, Rishita, King, Denise, Wittsack, Heather, Mendizabal, Adam, Devine, Steven M., Horowitz, Mary M., Chen, Yi-Bin, Agura, Ed, Altman, Jessica, Anagnostopoulos, Achiles, Anand, Sarah, Artz, Andrew, Aulitzky, Walter, Balderman, Sophia, Ballen, Karen, Becker, Michael, Beguin, Yves, Berkahn, Leanne, Berneman, Zwi, Bhatt, Vijaya, Bilmon, Ian, Bonifazi, Francesca, Briggs, Adrienne, Bruno, Benedetto, Brunstein, Claudio, Byrne, Michael, Byrne, Jenny, Cabrero, Monica, Cairoli, Roberto, Carrum, George, Cerny, Jan, Cheong, June-Won, Ciceri, Fabio, Colorado, Mercedes, Cook, Rachel, Couriel, Daniel, Craddock, Charles, Damon, Lloyd, Deol, Abhinav, Desbrosses, Yohan, Devine, Steve, Di Grazia, Carmela, Di Stasi, Antonio, Dias, Ajoy, Dorritie, Kathy, Essell, James, Eto, Tetsuya, Farag, Sherif, Forcade, Edouard, Frankfurt, Olga, Fujiwara, Shinichiro, Fukuda, Takahiro, Fukushima, Kentaro, Furst, Sabine, Goto, Tatsunori, Hall, Aric, Hatta, Shunsuke, Hicheri, Yosr, Horwitz, Mitchell, Hou, Hsin-An, How, Jonathan, Howard, Dianna, Hsu, Wei-Hsun (Blake), Huynh, Anne, Irvine, David, Ishikawa, Takayuki, Jamieson, Katarzyna, Jedrzejczak, Wieslaw, Jethava, Yogesh, Jimenez, Antonio, Jung, Chul Won, Kanda, Junya, Karakasis, Dimitrios, Kato, Jun, Kekre, Natasha, Khera, Nandita, Klein, Andreas, Kobbe, Guido, Kornblit, Brian, Kota, Vamsi, Lachance, Silvy, Leber, Brian, Lee, Catherine, Lee, Je Hwan, Lin, Tung-Liang, Liu, Ta-Chih, Martelli, Maurizio, Martinez, Carmen, Matsuoka, Kenichi, McCarty, John, Mendez, Lourdes, Michelis, Fotios, Mineishi, Shin, Mohty, Mohamad, Moors, Ine, Motyckova, Gabriela, Mueller, Lutz, Nakamae, Hirohisa, Nakano, Nobuaki, Nathan, Sunita, Nicholson, Emma, Norkin, Maxim, Ogawa, Yoshiaki, Olesen, Gitte, Oluwole, Olalekan, Pantin, Jeremy, Paulson, Kristjan, Pemberton, Lucy, Perera, Travis, Piatkowska-Jakubas, Beata, Poire, Xavier, Protheroe, Rachel, Rambaldi, Alessandro, Ritchie, David, Ross, Kelly, Rubio, Marie-Therese, Santarone, Stella, Sanz Caballer, Jaime, Sawa, Masashi, Schaar, Dale, Scheid, Christoph, Schriber, Jeffrey, Seropian, Stuart, Shah, Nilay, Shah, Nirav, Shore, Tsiporah, Gil, Jorge Sierra, Singh, Anurag, Sobecks, Ronald, Socie, Gerard, Soiffer, Robert, Sprague, Kellie, Spyridonidis, Alexandros, Stelljes, Matthias, Stiff, Patrick, Stuart, Robert, Tanaka, Masatsugu, Tandra, Anand, Tholouli, Eleni, Thomas, Xavier, Tiribelli, Mario, Tomlinson, Benjamin, Tsirigotis, Panagiotis, Tzachanis, Dimitrios, Uchida, Naoyuki, Ueda, Masumi, Valcarcel Ferreiras, David, Wagner, Eva, Watson, Anne-Marie, Weisdorf, Daniel, Wolschke, Christine, Wrobel, Tomasz, Yakoub-Agha, Ibrahim, Yamauchi, Takuji, Yared, Jean, Yeh, Su-Peng, Yoon, Sung-Soo, Yoshihara, Satoshi, null, null, Levis, M, Hamadani, M, Logan, B, Jones, R, Singh, A, Litzow, M, Wingard, J, Papadopoulos, E, Perl, A, Soiffer, R, Ustun, C, Ueda Oshima, M, Uy, G, Waller, E, Vasu, S, Solh, M, Mishra, A, Muffly, L, Kim, H, Mikesch, J, Najima, Y, Onozawa, M, Thomson, K, Nagler, A, Wei, A, Marcucci, G, Geller, N, Hasabou, N, Delgado, D, Rosales, M, Hill, J, Gill, S, Nuthethi, R, King, D, Wittsack, H, Mendizabal, A, Devine, S, Horowitz, M, Chen, Y, Agura, E, Altman, J, Anagnostopoulos, A, Anand, S, Artz, A, Aulitzky, W, Balderman, S, Ballen, K, Becker, M, Beguin, Y, Berkahn, L, Berneman, Z, Bhatt, V, Bilmon, I, Bonifazi, F, Briggs, A, Bruno, B, Brunstein, C, Byrne, M, Byrne, J, Cabrero, M, Cairoli, R, Carrum, G, Cerny, J, Cheong, J, Ciceri, F, Colorado, M, Cook, R, Couriel, D, Craddock, C, Damon, L, Deol, A, Desbrosses, Y, Di Grazia, C, Di Stasi, A, Dias, A, Dorritie, K, Essell, J, Eto, T, Farag, S, Forcade, E, Frankfurt, O, Fujiwara, S, Fukuda, T, Fukushima, K, Furst, S, Goto, T, Hall, A, Hatta, S, Hicheri, Y, Horwitz, M, Hou, H, How, J, Howard, D, Hsu, W, Huynh, A, Irvine, D, Ishikawa, T, Jamieson, K, Jedrzejczak, W, Jethava, Y, Jimenez, A, Jung, C, Kanda, J, Karakasis, D, Kato, J, Kekre, N, Khera, N, Klein, A, Kobbe, G, Kornblit, B, Kota, V, Lachance, S, Leber, B, Lee, C, Lee, J, Lin, T, Liu, T, Martelli, M, Martinez, C, Matsuoka, K, Mccarty, J, Mendez, L, Michelis, F, Mineishi, S, Mohty, M, Moors, I, Motyckova, G, Mueller, L, Nakamae, H, Nakano, N, Nathan, S, Nicholson, E, Norkin, M, Ogawa, Y, Olesen, G, Oluwole, O, Pantin, J, Paulson, K, Pemberton, L, Perera, T, Piatkowska-Jakubas, B, Poire, X, Protheroe, R, Rambaldi, A, Ritchie, D, Ross, K, Rubio, M, Santarone, S, Sanz Caballer, J, Sawa, M, Schaar, D, Scheid, C, Schriber, J, Seropian, S, Shah, N, Shore, T, Gil, J, Sobecks, R, Socie, G, Sprague, K, Spyridonidis, A, Stelljes, M, Stiff, P, Stuart, R, Tanaka, M, Tandra, A, Tholouli, E, Thomas, X, Tiribelli, M, Tomlinson, B, Tsirigotis, P, Tzachanis, D, Uchida, N, Ueda, M, Valcarcel Ferreiras, D, Wagner, E, Watson, A, Weisdorf, D, Wolschke, C, Wrobel, T, Yakoub-Agha, I, Yamauchi, T, Yared, J, Yeh, S, Yoon, S, Yoshihara, S, Null, N, Levis, Mark J., Hamadani, Mehdi, Logan, Brent, Jones, Richard J., Singh, Anurag K., Litzow, Mark, Wingard, John R., Papadopoulos, Esperanza B., Perl, Alexander E., Soiffer, Robert J., Ustun, Celalettin, Ueda Oshima, Masumi, Uy, Geoffrey L., Waller, Edmund K., Vasu, Sumithra, Solh, Melhem, Mishra, Asmita, Muffly, Lori, Kim, Hee-Je, Mikesch, Jan-Henrik, Najima, Yuho, Onozawa, Masahiro, Thomson, Kirsty, Nagler, Arnon, Wei, Andrew H., Marcucci, Guido, Geller, Nancy L., Hasabou, Nahla, Delgado, David, Rosales, Matt, Hill, Jason, Gill, Stanley C., Nuthethi, Rishita, King, Denise, Wittsack, Heather, Mendizabal, Adam, Devine, Steven M., Horowitz, Mary M., Chen, Yi-Bin, Agura, Ed, Altman, Jessica, Anagnostopoulos, Achiles, Anand, Sarah, Artz, Andrew, Aulitzky, Walter, Balderman, Sophia, Ballen, Karen, Becker, Michael, Beguin, Yves, Berkahn, Leanne, Berneman, Zwi, Bhatt, Vijaya, Bilmon, Ian, Bonifazi, Francesca, Briggs, Adrienne, Bruno, Benedetto, Brunstein, Claudio, Byrne, Michael, Byrne, Jenny, Cabrero, Monica, Cairoli, Roberto, Carrum, George, Cerny, Jan, Cheong, June-Won, Ciceri, Fabio, Colorado, Mercedes, Cook, Rachel, Couriel, Daniel, Craddock, Charles, Damon, Lloyd, Deol, Abhinav, Desbrosses, Yohan, Devine, Steve, Di Grazia, Carmela, Di Stasi, Antonio, Dias, Ajoy, Dorritie, Kathy, Essell, James, Eto, Tetsuya, Farag, Sherif, Forcade, Edouard, Frankfurt, Olga, Fujiwara, Shinichiro, Fukuda, Takahiro, Fukushima, Kentaro, Furst, Sabine, Goto, Tatsunori, Hall, Aric, Hatta, Shunsuke, Hicheri, Yosr, Horwitz, Mitchell, Hou, Hsin-An, How, Jonathan, Howard, Dianna, Hsu, Wei-Hsun (Blake), Huynh, Anne, Irvine, David, Ishikawa, Takayuki, Jamieson, Katarzyna, Jedrzejczak, Wieslaw, Jethava, Yogesh, Jimenez, Antonio, Jung, Chul Won, Kanda, Junya, Karakasis, Dimitrios, Kato, Jun, Kekre, Natasha, Khera, Nandita, Klein, Andreas, Kobbe, Guido, Kornblit, Brian, Kota, Vamsi, Lachance, Silvy, Leber, Brian, Lee, Catherine, Lee, Je Hwan, Lin, Tung-Liang, Liu, Ta-Chih, Martelli, Maurizio, Martinez, Carmen, Matsuoka, Kenichi, McCarty, John, Mendez, Lourdes, Michelis, Fotios, Mineishi, Shin, Mohty, Mohamad, Moors, Ine, Motyckova, Gabriela, Mueller, Lutz, Nakamae, Hirohisa, Nakano, Nobuaki, Nathan, Sunita, Nicholson, Emma, Norkin, Maxim, Ogawa, Yoshiaki, Olesen, Gitte, Oluwole, Olalekan, Pantin, Jeremy, Paulson, Kristjan, Pemberton, Lucy, Perera, Travis, Piatkowska-Jakubas, Beata, Poire, Xavier, Protheroe, Rachel, Rambaldi, Alessandro, Ritchie, David, Ross, Kelly, Rubio, Marie-Therese, Santarone, Stella, Sanz Caballer, Jaime, Sawa, Masashi, Schaar, Dale, Scheid, Christoph, Schriber, Jeffrey, Seropian, Stuart, Shah, Nilay, Shah, Nirav, Shore, Tsiporah, Gil, Jorge Sierra, Singh, Anurag, Sobecks, Ronald, Socie, Gerard, Soiffer, Robert, Sprague, Kellie, Spyridonidis, Alexandros, Stelljes, Matthias, Stiff, Patrick, Stuart, Robert, Tanaka, Masatsugu, Tandra, Anand, Tholouli, Eleni, Thomas, Xavier, Tiribelli, Mario, Tomlinson, Benjamin, Tsirigotis, Panagiotis, Tzachanis, Dimitrios, Uchida, Naoyuki, Ueda, Masumi, Valcarcel Ferreiras, David, Wagner, Eva, Watson, Anne-Marie, Weisdorf, Daniel, Wolschke, Christine, Wrobel, Tomasz, Yakoub-Agha, Ibrahim, Yamauchi, Takuji, Yared, Jean, Yeh, Su-Peng, Yoon, Sung-Soo, Yoshihara, Satoshi, and null, null

Abstract

PURPOSEAllogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit.METHODSAdults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS.RESULTSThree hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P =.0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P =.0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P =.575).CONCLUSIONAlthough the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Published
2024

29. BK virus–specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation

Author

Espada, Eduardo, Cheng, Matthew P., Kim, Haesook T., Woolley, Ann E., Avigan, Jason I., Forcade, Edouard, Soares, Maria V.D., Lacerda, João F., Nikiforow, Sarah, Gooptu, Mahasweta, Romee, Rizwan, Alyea, Edwin P., Armand, Philippe, Cutler, Corey S., Ho, Vincent T., Koreth, John, Antin, Joseph H., Soiffer, Robert J., Marty, Francisco M., and Ritz, Jerome

Published
2020
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30. Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation

Author

Lewis, Clinton, Kim, Haesook T., Roeker, Lindsey E., Cutler, Corey, Koreth, John, Nikiforow, Sarah, Armand, Philippe, Gootpu, Mahasweta, Romee, Rizwan, Glotzbecker, Brett, Nageshwar, Prashant, Antin, Joseph H., Alyea, Edwin P., Richardson, Paul, Soiffer, Robert J., and Ho, Vincent T.

Published
2020
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31. Health-Related Quality of Life with Gilteritinib Versus Placebo Post-Transplant Maintenance for FLT3-ITD+ Acute Myeloid Leukemia (AML): A Quality of Life Analysis from BMT CTN 1506

Author

Hamilton, Betty K., primary, Levis, Mark J., additional, Pandya, Bhavik J, additional, Elsouda, Dina, additional, Logan, Brent, additional, Chen, Dr. Yi-Bin, additional, Hamadani, Mehdi, additional, Ueda, Masumi, additional, Perl, Alexander E., additional, Singh, Anurag K., additional, Soiffer, Robert J., additional, Litzow, Mark R., additional, Ustun, Celalettin, additional, Rosales, Matt, additional, Ivanescu, Cristina, additional, Cella, David, additional, Hasabou, Nahla, additional, Corredoira, Laura, additional, Pestana, Carolina, additional, and Horowitz, Mary M., additional

Published
2024
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32. CTLA-4 Blockade Leads to Enrichment of Active CD56dimCD16+ NK Cells and Depletion of Regulatory T Cells Following Infusion of Haploidentical Donor Memory-like Natural Killer Cells Plus IL-15 Superagonist in a Phase 1 Trial

Author

Shapiro, Roman M., primary, Sheffer, Michal, additional, Ansuinelli, Michela, additional, Booker, Matthew Aaron, additional, Tolstorukov, Michael Yevgeniy, additional, Dulery, Remy, additional, Sade-Feldman, Moshe, additional, Fang, Jacy, additional, Birch, Grace, additional, Vergara-Cadavid, Juliana, additional, Abdulhamid, Yasmin Z, additional, Kaplan, Isabel E, additional, Khanhlinh, Dinh, additional, Redd, Robert A, additional, Alonso, Alejandro, additional, Bat-Erdene, Denbaa, additional, Uppaluri, Ravindra, additional, Daly, Heather, additional, Hernandez-Rodriguez, Diego E, additional, Koreth, John, additional, Ritz, Jerome, additional, Nikiforow, Sarah, additional, Soiffer, Robert J., additional, Hanna, Glenn J, additional, and Romee, Rizwan, additional

Published
2024
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34. Ipilimumab for Patients with Relapse after Allogeneic Transplantation

Author

Davids, Matthew S, Kim, Haesook T, Bachireddy, Pavan, Costello, Caitlin, Liguori, Rebecca, Savell, Alexandra, Lukez, Alexander P, Avigan, David, Chen, Yi-Bin, McSweeney, Peter, LeBoeuf, Nicole R, Rooney, Michael S, Bowden, Michaela, Zhou, Chensheng W, Granter, Scott R, Hornick, Jason L, Rodig, Scott J, Hirakawa, Masahiro, Severgnini, Mariano, Hodi, F Stephen, Wu, Catherine J, Ho, Vincent T, Cutler, Corey, Koreth, John, Alyea, Edwin P, Antin, Joseph H, Armand, Philippe, Streicher, Howard, Ball, Edward D, Ritz, Jerome, Bashey, Asad, and Soiffer, Robert J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Research, Hematology, Regenerative Medicine, Pediatric, Patient Safety, Stem Cell Research - Nonembryonic - Non-Human, Cancer, Rare Diseases, Pediatric Cancer, Clinical Trials and Supportive Activities, Stem Cell Research, Transplantation, Stem Cell Research - Nonembryonic - Human, 6.2 Cellular and gene therapies, 5.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Evaluation of treatments and therapeutic interventions, Adult, Aged, Antibodies, Monoclonal, CD4 Lymphocyte Count, Female, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Induction Chemotherapy, Ipilimumab, Leukemia, Lymphoma, Male, Middle Aged, Myeloproliferative Disorders, Recurrence, T-Lymphocytes, Regulatory, Transplantation Immunology, Transplantation, Homologous, Leukemia and Lymphoma Society Blood Cancer Research Partnership, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundLoss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect.MethodsWe conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit.ResultsA total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood.ConclusionsOur early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01822509.).

Published
2016

35. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

Author

Townsend, Elizabeth C, Murakami, Mark A, Christodoulou, Alexandra, Christie, Amanda L, Köster, Johannes, DeSouza, Tiffany A, Morgan, Elizabeth A, Kallgren, Scott P, Liu, Huiyun, Wu, Shuo-Chieh, Plana, Olivia, Montero, Joan, Stevenson, Kristen E, Rao, Prakash, Vadhi, Raga, Andreeff, Michael, Armand, Philippe, Ballen, Karen K, Barzaghi-Rinaudo, Patrizia, Cahill, Sarah, Clark, Rachael A, Cooke, Vesselina G, Davids, Matthew S, DeAngelo, Daniel J, Dorfman, David M, Eaton, Hilary, Ebert, Benjamin L, Etchin, Julia, Firestone, Brant, Fisher, David C, Freedman, Arnold S, Galinsky, Ilene A, Gao, Hui, Garcia, Jacqueline S, Garnache-Ottou, Francine, Graubert, Timothy A, Gutierrez, Alejandro, Halilovic, Ensar, Harris, Marian H, Herbert, Zachary T, Horwitz, Steven M, Inghirami, Giorgio, Intlekofer, Andrew M, Ito, Moriko, Izraeli, Shai, Jacobsen, Eric D, Jacobson, Caron A, Jeay, Sébastien, Jeremias, Irmela, Kelliher, Michelle A, Koch, Raphael, Konopleva, Marina, Kopp, Nadja, Kornblau, Steven M, Kung, Andrew L, Kupper, Thomas S, LeBoeuf, Nicole R, LaCasce, Ann S, Lees, Emma, Li, Loretta S, Look, A Thomas, Murakami, Masato, Muschen, Markus, Neuberg, Donna, Ng, Samuel Y, Odejide, Oreofe O, Orkin, Stuart H, Paquette, Rachel R, Place, Andrew E, Roderick, Justine E, Ryan, Jeremy A, Sallan, Stephen E, Shoji, Brent, Silverman, Lewis B, Soiffer, Robert J, Steensma, David P, Stegmaier, Kimberly, Stone, Richard M, Tamburini, Jerome, Thorner, Aaron R, van Hummelen, Paul, Wadleigh, Martha, Wiesmann, Marion, Weng, Andrew P, Wuerthner, Jens U, Williams, David A, Wollison, Bruce M, Lane, Andrew A, Letai, Anthony, Bertagnolli, Monica M, Ritz, Jerome, Brown, Myles, Long, Henry, Aster, Jon C, Shipp, Margaret A, Griffin, James D, and Weinstock, David M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Clinical Trials and Supportive Activities, Orphan Drug, Clinical Research, Hematology, Cancer, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Animals, Antineoplastic Agents, Biomarkers, Tumor, Cell Lineage, Female, Gene Expression Profiling, Genes, p53, Heterografts, Humans, Internet, Isoquinolines, Leukemia, Leukemia, Experimental, Lymphoma, Male, Mice, Mice, Inbred NOD, Molecular Targeted Therapy, Neoplasm Proteins, Neoplasm Transplantation, Phenotype, Piperazines, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Proteome, Proto-Oncogene Proteins c-mdm2, Random Allocation, Randomized Controlled Trials as Topic, Research Design, Tissue Banks, Transcriptome, Xenograft Model Antitumor Assays, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.

Published
2016

36. Clinical Features of Acute Kidney Injury in the Early Post-Transplantation Period Following Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation

Author

Vergara-Cadavid, Juliana, Johnson, P. Connor, Kim, Haesook T., Yi, Alisha, Sise, Meghan E., Leaf, David E., Hanna, Paul E., Ho, Vincent T., Cutler, Corey S., Antin, Joseph H., Gooptu, Mahasweta, Kelkar, Amar H., Wells, Sophia L., Nikiforow, Sarah, Koreth, John, Romee, Rizwan, Soiffer, Robert J., Shapiro, Roman M., and Gupta, Shruti

Published
2023
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37. Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease

Author

Divito, Sherrie J., Aasebo, Anders T., Matos, Tiago R., Hsieh, Pei-Chen, Collin, Matthew, Elco, Christopher P., O'Malley, John T., Baekkevold, Espen S., Reims, Henrik, Gedde-Dahl, Tobias, Hagerstrom, Michael, Hilaire, Jude, Lian, John W., Milford, Edgar L., Pinkus, Geraldine S., Ho, Vincent T., Soiffer, Robert J., Kim, Haesook T., Mihm, Martin C., Ritz, Jerome, Guleria, Indira, Cutler, Corey S., Clark, Rachael A., Jahnsen, Frode L., and Kupper, Thomas S.

Subjects
Thermo Fisher Scientific Inc., Medical research -- Health aspects, Skin -- Health aspects, Hematopoietic stem cell transplantation -- Health aspects, Stem cells -- Health aspects, Scientific equipment industry -- Health aspects, T cells -- Health aspects, Health care industry
Abstract

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Donor T cells are key mediators in pathogenesis, but a contribution from host T cells has not been explored, as conditioning regimens are believed to deplete host T cells. To evaluate a potential role for host T cells in GVHD, the origin of skin and blood T cells was assessed prospectively in patients after HSCT in the absence of GVHD. While blood contained primarily donor-derived T cells, most T cells in the skin were host derived. We next examined patient skin, colon, and blood during acute GVHD. Host T cells were present in all skin and colon acute GVHD specimens studied, yet were largely absent in blood. We observed acute skin GVHD in the presence of 100% host T cells. Analysis demonstrated that a subset of host T cells in peripheral tissues were proliferating ([Ki67.sup.+]) and producing the proinflammatory cytokines IFN-[gamma] and IL-17 in situ. Comparatively, the majority of antigen-presenting cells (APCs) in tissue in acute GVHD were donor derived, and donor-derived APCs were observed directly adjacent to host T cells. A humanized mouse model demonstrated that host skin-resident T cells could be activated by donor monocytes to generate a GVHD-like dermatitis. Thus, host tissue-resident T cells may play a previously unappreciated pathogenic role in acute GVHD., Introduction Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) (1-6). Current dogma holds that donor T cells, either transferred with or [...]

Published
2020
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40. Dose-escalated interleukin-2 therapy for refractory chronic graft-versus-host disease in adults and children

Author

Whangbo, Jennifer S., Kim, Haesook T., Mirkovic, Nikola, Leonard, Lauren, Poryanda, Samuel, Silverstein, Sophie, Kim, Soomin, Reynolds, Carol G., Rai, Sharmila C., Verrill, Kelly, Lee, Michelle A., Margossian, Steven, Duncan, Christine, Lehmann, Leslie, Huang, Jennifer, Nikiforow, Sarah, Alyea, Edwin P., III, Armand, Philippe, Cutler, Corey S., Ho, Vincent T., Blazar, Bruce R., Antin, Joseph H., Soiffer, Robert J., Ritz, Jerome, and Koreth, John

Published
2019
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42. Active infection at the time of CD34+selected stem cell boost is associated with treatment failure and poor overall survival

Author

Shapiro, Roman M., Kim, Haesook T., Dulery, Remy, Liney, Deborah, Garrity, Heather M., Panaro, Kevin, Au, Chloe, Gervais, Casey, Little, Jessica S., Ho, Vincent T., Cutler, Corey S., Koreth, John, Gooptu, Mahasweta, Antin, Joseph H., Kelkar, Amar H., Romee, Rizwan, Wu, Catherine J., Ritz, Jerome, Soiffer, Robert J., and Nikiforow, Sarah

Abstract

•CD34+selected SCB can restore hematopoiesis after PGF after allogeneic hematopoietic stem cell transplant.•An active infection at the time of CD34+selected SCB is the strongest predictor of treatment failure and poor overall survival.

Published
2024
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43. Ibrutinib treatment ameliorates murine chronic graft-versus-host disease

Author

Dubovsky, Jason A, Flynn, Ryan, Du, Jing, Harrington, Bonnie K, Zhong, Yiming, Kaffenberger, Benjamin, Yang, Carrie, Towns, William H, Lehman, Amy, Johnson, Amy J, Muthusamy, Natarajan, Devine, Steven M, Jaglowski, Samantha, Serody, Jonathan S, Murphy, William J, Munn, David H, Luznik, Leo, Hill, Geoffrey R, Wong, Henry K, MacDonald, Kelli KP, Maillard, Ivan, Koreth, John, Elias, Laurence, Cutler, Corey, Soiffer, Robert J, Antin, Joseph H, Ritz, Jerome, Panoskaltsis-Mortari, Angela, Byrd, John C, and Blazar, Bruce R

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Immunology, Stem Cell Research - Nonembryonic - Non-Human, Hematology, Rare Diseases, Transplantation, Orphan Drug, Regenerative Medicine, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adenine, Animals, Disease-Free Survival, Drug Evaluation, Preclinical, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Immunologic Factors, Lymphocyte Activation, Mice, Inbred C57BL, Piperidines, Pyrazoles, Pyrimidines, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Chronic graft-versus-host disease (cGVHD) is a life-threatening impediment to allogeneic hematopoietic stem cell transplantation, and current therapies do not completely prevent and/or treat cGVHD. CD4+ T cells and B cells mediate cGVHD; therefore, targeting these populations may inhibit cGVHD pathogenesis. Ibrutinib is an FDA-approved irreversible inhibitor of Bruton's tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissions in B cell malignancies with minimal toxicity. Here, we evaluated whether ibrutinib could reverse established cGVHD in 2 complementary murine models, a model interrogating T cell-driven sclerodermatous cGVHD and an alloantibody-driven multiorgan system cGVHD model that induces bronchiolar obliterans (BO). In the T cell-mediated sclerodermatous cGVHD model, ibrutinib treatment delayed progression, improved survival, and ameliorated clinical and pathological manifestations. In the alloantibody-driven cGVHD model, ibrutinib treatment restored pulmonary function and reduced germinal center reactions and tissue immunoglobulin deposition. Animals lacking BTK and ITK did not develop cGVHD, indicating that these molecules are critical to cGVHD development. Furthermore, ibrutinib treatment reduced activation of T and B cells from patients with active cGVHD. Our data demonstrate that B cells and T cells drive cGVHD and suggest that ibrutinib has potential as a therapeutic agent, warranting consideration for cGVHD clinical trials.

Published
2014

44. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases.

Author

Henrich, Timothy J, Hanhauser, Emily, Marty, Francisco M, Sirignano, Michael N, Keating, Sheila, Lee, Tzong-Hae, Robles, Yvonne P, Davis, Benjamin T, Li, Jonathan Z, Heisey, Andrea, Hill, Alison L, Busch, Michael P, Armand, Philippe, Soiffer, Robert J, Altfeld, Marcus, and Kuritzkes, Daniel R

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Stem Cell Research, Infectious Diseases, Regenerative Medicine, Transplantation, Stem Cell Research - Nonembryonic - Human, HIV/AIDS, Clinical Research, Infection, Good Health and Well Being, Antiretroviral Therapy, Highly Active, DNA, Viral, HIV Infections, HIV-1, Hematopoietic Stem Cell Transplantation, Hodgkin Disease, Humans, Intestinal Mucosa, Male, Myelodysplastic Syndromes, RNA, Viral, Rectum, Remission Induction, Viremia, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundIt is unknown whether the reduction in HIV-1 reservoirs seen after allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission.ObjectiveTo characterize HIV-1 reservoirs in blood and tissues and perform analytic antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained, antiretroviral-free HIV-1 remission.DesignCase report with characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption.SettingTertiary care center.PatientsTwo men with HIV with undetectable HIV-1 after allogeneic HSCT for hematologic tumors.MeasurementsQuantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption.ResultsNo HIV-1 was detected from peripheral blood or rectal mucosa before analytic treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 and 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia within 2 weeks of the most recent negative viral load measurement and developed symptoms consistent with the acute retroviral syndrome. One patient developed new efavirenz resistance after reinitiation of antiretroviral therapy. Reinitiation of active therapy led to viral decay and resolution of symptoms in both patients.LimitationThe study involved only 2 patients.ConclusionAllogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. The definition of the nature and half-life of such reservoirs is essential to achieve durable antiretroviral-free HIV-1 remission.Primary funding sourceFoundation for AIDS Research and National Institute of Allergy and Infectious Diseases.

Published
2014

45. Clinical outcomes and evolution of clonal hematopoiesis in patients with newly diagnosed multiple myeloma

Author

Mouhieddine, Tarek H, primary, Nzerem, Chidimma, additional, Redd, Robert, additional, Dunford, Andrew, additional, Leventhal, Matthew, additional, Sklavenitis-Pistofidis, Romanos, additional, Tahri, Sabrin, additional, El-Khoury, Habib, additional, Steensma, David P, additional, Ebert, Benjamin L., additional, Soiffer, Robert J., additional, Keats, Jonathan J, additional, Mehr, Shaadi, additional, Auclair, Daniel, additional, Ghobrial, Irene M, additional, Sperling, Adam S., additional, Stewart, Chip, additional, and Getz, Gad, additional

Published
2023
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46. Immune control in repeated Babesia microti infection in a B cell-deficient patient

Author

Little, Jessica S, primary, Oakley, Miranda S, additional, Thorner, Anna, additional, Johnston, Demerise, additional, Majam, Victoria, additional, Liakos, Alexis D, additional, Novack, Lewis A, additional, Zheng, Hong, additional, Meredith, Scott, additional, Chou, Chao-Kai, additional, Newton, Benjamin R, additional, Soiffer, Robert J, additional, Krause, Peter J, additional, Baden, Lindsey R, additional, and Kumar, Sanjai, additional

Published
2023
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47. Opportunistic Infections in Patients Receiving Post-Transplantation Cyclophosphamide: Impact of Haploidentical versus Unrelated Donor Allograft

Author

Little, Jessica S., primary, Duléry, Rémy, additional, Shapiro, Roman M., additional, Aleissa, Muneerah M., additional, Prockop, Susan E., additional, Koreth, John, additional, Ritz, Jerome, additional, Antin, Joseph H., additional, Cutler, Corey, additional, Nikiforow, Sarah, additional, Romee, Rizwan, additional, Issa, Nicolas C., additional, Ho, Vincent T., additional, Baden, Lindsey R., additional, Soiffer, Robert J., additional, and Gooptu, Mahasweta, additional

Published
2023
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48. Expansion, persistence, and efficacy of donor memory-like NK cells infused for posttransplant relapse

Author

Shapiro, Roman M., Birch, Grace C., Hu, Guangan, Cadavid, Juliana Vergara, Nikiforow, Sarah, Baginska, Joanna, Ali, Alaa K., Tarannum, Mubin, Sheffer, Michal, Abdulhamid, Yasmin Z., Rambaldi, Benedetta, Arihara, Yohei, Reynolds, Carol, Halpern, Max S., Rodig, Scott J., Cullen, Nicole, Wolff, Jacquelyn O., Pfaff, Kathleen L., Lane, Andrew A., Lindsley, R. Coleman, Cutler, Corey S., Antin, Joseph H., Ho, Vincent T., Koreth, John, Gooptu, Mahasweta, Kim, Haesook T., Malmberg, Karl-Johan, Wu, Catherine J., Chen, Jianzhu, Soiffer, Robert J., Ritz, Jerome, and Romee, Rizwan

Subjects
Diseases -- Relapse, Killer cells -- Physiological aspects -- Usage -- Health aspects, Hematopoietic stem cells -- Transplantation, Health care industry
Abstract

BACKGROUND. Responses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell-based therapy is a promising modality to treat post-HCT relapse. METHODS. We initiated this ongoing phase I trial of adoptively transferred cytokine-induced memory-like (CIML) NK cells in patients with myeloid malignancies who relapsed after haploidentical HCT. All patients received a donor-derived NK cell dose of 5 to 10 million cells/kg after lymphodepleting chemotherapy, followed by systemic IL-2 for 7 doses. Highresolution profiling with mass cytometry and single-cell RNA sequencing characterized the expanding and persistent NK cell subpopulations in a longitudinal manner after infusion. RESULTS. In the first 6 enrolled patients on the trial, infusion of CIML NK cells led to a rapid 10- to 50-fold in vivo expansion that was sustained over months. The infusion was well tolerated, with fever and pancytopenia as the most common adverse events. Expansion of NK cells was distinct from IL-2 effects on endogenous post-HCT NK cells, and not dependent on CMV viremia. Immunophenotypic and transcriptional profiling revealed a dynamic evolution of the activated CIML NK cell phenotype, superimposed on the natural variation in donor NK cell repertoires. CONCLUSION. Given their rapid expansion and long-term persistence in an immune-compatible environment, CIML NK cells serve as a promising platform for the treatment of posttransplant relapse of myeloid disease. Further characterization of their unique in vivo biology and interaction with both T cells and tumor targets will lead to improvements in cell-based immunotherapies. TRIAL REGISTRATION. ClinicalTrials.gov NCT04024761. FUNDING. Dunkin' Donuts, NIH/National Cancer Institute, and the Leukemia and Lymphoma Society., Introduction Relapse of acute myeloid leukemia (AML) occurs in up to 50% of patients after allogeneic hematopoietic stem cell transplant (HCT) and heralds an extremely poor prognosis (1). In several [...]

Published
2022
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