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ABBV-319: a CD19–targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies Blood (IF 20.3) Pub Date : 2024-05-06 Chewei Anderson Chang, Ethan Emberley, Aloma L. D'Souza, Weilong Zhao, Cormac Cosgrove, Karen Parrish, Diya Mitra, Elmer Payson, Anatol Oleksijew, Paul Ellis, Luis Rodriguez, Ryan Duggan, Cara Hrusch, Loren Lasko, Wissam Assaily, Pingping Zheng, Wei Liu, Axel Hernandez Jr., Kimberley McCarthy, Zhaomei Zhang, Geunbae Rha, Zhensheng Cao, Yingchun Li, Olivia Perng, Jos Campbell, Gloria Zhang, Tyler Curran
Glucocorticoids are key components of the current standard-of-care regimens (eg, R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab], and hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine]) for the treatment of B-cell malignancy. However
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Motive and opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements (an LLMPP study) Blood (IF 20.3) Pub Date : 2024-05-06 Laura K. Hilton, Brett Collinge, Susana Ben-Neriah, Waleed Alduaij, Haya Shaalan, Andrew P. Weng, Manuela Cruz, Graham W. Slack, Pedro Farinha, Tomoko Miyata-Takata, Merrill Boyle, Barbara Meissner, James R. Cook, Sarah L. Ondrejka, German Ott, Andreas Rosenwald, Elias Campo, Catalina Amador, Timothy C. Greiner, Philipp W. Raess, Joo Y. Song, Giorgio Inghirami, Elaine S. Jaffe, Dennis D. Weisenburger
Rearrangements that place the oncogenes , , or adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both and rearrangements are classified as high-grade B-cell lymphoma with and rearrangements (“double hit”; HGBCL-DH-) and are associated with aggressive disease and poor outcomes. Although it is established
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CAR T cells vs bispecific antibody as third- or later-line large B-cell lymphoma therapy: a meta-analysis Blood (IF 20.3) Pub Date : 2024-05-06 Jinchul Kim, Jinhyun Cho, Moon Hee Lee, Sang Eun Yoon, Won Seog Kim, Seok Jin Kim
This meta-analysis evaluates the efficacy and safety of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). We searched MEDLINE, Embase, and Cochrane databases until July 2023 for trials assessing CAR T-cell therapies and CD20×CD3 bispecific antibodies as third or subsequent lines in R/R DLBCL. Random-effects models
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Impact of hematopoietic cell transplantation on myocardial fibrosis in young patients with sickle cell disease Blood (IF 20.3) Pub Date : 2024-05-03 Akshay Sharma, Subodh Selukar, Yu Bi, Anthony Merlocco, Cara E. Morin, Chris Goode, Parul Rai, Jeffrey A. Towbin, Jane S. Hankins, Stephen Gottschalk, Brandon Triplett, Jason N. Johnson
Serial cardiovascular magnetic resonance evaluation of children and young adults with sickle cell disease who underwent hematopoietic cell transplantation showed mean ECV, representing diffuse myocardial fibrosis, decreased 3.4% from baseline to 12-months post-HCT. This trial was registered at as #NCT04362293.
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Molecular, clinical, and therapeutic determinants of outcome in NPM1 mutated AML Blood (IF 20.3) Pub Date : 2024-05-03 Jad Othman, Nicola Potter, Adam Ivey, Yanis Tazi, Elli Papaemmanuil, Jelena Jovanovic, Sylvie D. Freeman, Amanda Gilkes, Rosemary Gale, Tanya Rapoz-D’Silva, Manohursingh Runglall, Michelle Kleeman, Pawan Dhami, Ian Thomas, Sean Johnson, Joanna Canham, Jamie Cavenagh, Panagiotis Kottaridis, Claire Arnold, Hans Beier Ommen, Ulrik Malthe Overgaard, Mike Dennis, Alan Burnett, Charlotte Wilhelm-Benartzi
Although -mutated acute myeloid leukemia (AML) carries a generally favorable prognosis, many patients still relapse and die. Previous studies identified several molecular and clinical features associated with poor outcomes; however, only -internal tandem duplication (ITD) mutation and adverse karyotype are currently used for risk stratification because of inconsistent results and uncertainty about
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Kinase-inactivated CDK6 preserves the long-term functionality of adult hematopoietic stem cells Blood (IF 20.3) Pub Date : 2024-05-03 Isabella M. Mayer, Eszter Doma, Thorsten Klampfl, Michaela Prchal-Murphy, Sebastian Kollmann, Alessia Schirripa, Lisa Scheiblecker, Markus Zojer, Natalia Kunowska, Lea Gebrail, Lisa E. Shaw, Ulrike Mann, Alex Farr, Reinhard Grausenburger, Gerwin Heller, Eva Zebedin-Brandl, Matthias Farlik, Marcos Malumbres, Veronika Sexl, Karoline Kollmann
Hematopoietic stem cells (HSCs) are characterized by the ability to self-renew and to replenish the hematopoietic system. The cell-cycle kinase cyclin-dependent kinase 6 (CDK6) regulates transcription, whereby it has both kinase-dependent and kinase-independent functions. Herein, we describe the complex role of CDK6, balancing quiescence, proliferation, self-renewal, and differentiation in activated
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T-bet suppresses proliferation of malignant B cells in chronic lymphocytic leukemia Blood (IF 20.3) Pub Date : 2024-05-02 Philipp M. Roessner, Isabelle Seufert, Vicente Chapaprieta, Ruparoshni Jayabalan, Hannah Briesch, Ramon Massoni-Badosa, Pavle Boskovic, Julian Beckendorff, Tobias Roider, Lavinia Arseni, Mariana Coelho, Supriya Chakraborty, Alicia M. Vaca, Mariela Sivina, Markus Muckenhuber, Sonia Rodriguez-Rodriguez, Alice Bonato, Sophie A. Herbst, Marc Zapatka, Clare Sun, Helene Kretzmer, Thomas Naake, Peter-Martin
The T-box transcription factor T-bet is known as a master regulator of the T-cell response but its role in malignant B cells has not been sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with a genetic knockout of . We found that T-bet acts as a tumor suppressor
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Outcomes of HLA-mismatched HSCT with TCRαβ/CD19 depletion or post-HSCT cyclophosphamide for inborn errors of immunity Blood (IF 20.3) Pub Date : 2024-04-30 Su Han Lum, Michael H. Albert, Patrick Gilbert, Tiarlan Sirait, Mattia Algeri, Rafaella Muratori, Benjamin Fournier, Alexandra Laberko, Musa Karakukcu, Unal Ekrem, Mouhab Ayas, Satya Prakash Yadav, Tunc Fisgin, Reem Elfeky, Juliana Fernandes, Maura Faraci, Theresa Cole, Ansgar Schulz, Roland Meisel, Marco Zecca, Marianne Ifversen, Alessandra Biffi, Jean Sebastien Diana, Tanja Vallée, Stefano Giardino
HLA-mismatched transplants with either in vitro depletion of CD3 T-cell receptor (TCR)αβ/CD19 (TCRαβ) cells or in vivo T-cell depletion using posttransplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEIs). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEIs undergoing their first transplant between 2010
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High efficacy of CD19 CAR T cells in patients with transformed Waldenström macroglobulinemia Blood (IF 20.3) Pub Date : 2024-04-30 Eric Durot, Damien Roos-Weil, Adrien Chauchet, Justine Decroocq, Roberta Di Blasi, Thomas Gastinne, Hedi Bensaber, Morgane Cheminant, Caroline Jacquet, Stéphanie Guidez, François-Xavier Gros, Emmanuel Bachy, Arthur Coste, Pascale Cony-Makhoul, Steven P. Treon, Alain Delmer, Ran Reshef, Steven Le Gouill, Jorge J. Castillo, Roch Houot
Histologic transformation of Waldenström macroglobulinemia (HT-WM) carries a poor prognosis with standard treatments. Here, we report the first series of HT-WM treated with chimeric antigen receptor T cells showing a high efficacy and no unexpected toxicity.
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Obinutuzumab vs rituximab for transplant-eligible patients with mantle cell lymphoma Blood (IF 20.3) Pub Date : 2024-04-29 Clémentine Sarkozy, Mary Callanan, Catherine Thieblemont, Lucie Oberic, Barbara Burroni, Krimo Bouabdallah, Gandhi Damaj, Benoit Tessoulin, Vincent Ribrag, Roch Houot, Franck Morschhauser, Samuel Griolet, Clémentine Joubert, Victoria Cacheux, Vincent Delwail, Violaine Safar, Remy Gressin, Morgane Cheminant, Marie-Hélène Delfau-Larue, Olivier Hermine, Elizabeth Macintyre, Steven Le Gouill
Obinutuzumab (O) and rituximab (R) are 2 CD antibodies that have never been compared in a prospective randomized trial of mantle cell lymphoma (MCL). Herein, we report the long-term outcome of the LYMA-101 trial , in which newly diagnosed patients with MCL were treated with chemotherapy plus O before transplantation, followed by O maintenance (O group). We then compared these patients with those treated
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Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses and treatment-free remissions Blood (IF 20.3) Pub Date : 2024-04-29 Sasanka M. Handunnetti, Mary Ann Anderson, Kate Burbury, Philip A. Thompson, Glenda Burke, Mathias Bressel, Juliana Di Iulio, Rodney J. Hicks, David Westerman, Stephen Lade, Christiane Pott, Rishu Agarwal, Rachel Koldej, David Ritchie, Martin Dreyling, Mark A. Dawson, Sarah-Jane Dawson, John F. Seymour, Andrew W. Roberts, Constantine S. Tam
In the phase 2 clinical trial (AIM) of venetoclax-ibrutinib, 24 patients with mantle cell lymphoma (MCL; 23 with relapsed/refractory [R/R] disease) received ibrutinib 560 mg and venetoclax 400 mg both once daily. High complete remission (CR) and measurable residual disease negative (MRD-negative) CR rates were previously reported. With median survivor follow-up now exceeding 7 years, we report long-term
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Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation Blood (IF 20.3) Pub Date : 2024-04-29 Clara Philine Wienecke, Bennet Heida, Letizia Venturini, Razif Gabdoulline, Katja Krüger, Katrin Teich, Konstantin Büttner, Martin Wichmann, Wolfram Puppe, Blerina Neziri, Marlene Reuter, Elke Dammann, Michael Stadler, Arnold Ganser, Lothar Hambach, Felicitas Thol, Michael Heuser
Patients with acute myeloid leukemia (AML) who experience relapse following allogeneic hematopoietic cell transplantation (alloHCT) face unfavorable outcomes regardless of the chosen relapse treatment. Early detection of relapse at the molecular level by measurable residual disease (MRD) assessment enables timely intervention, which may prevent hematological recurrence of the disease. It remains unclear
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Gasdermin D drives focal crystalline thrombotic microangiopathy by accelerating immunothrombosis and necroinflammation Blood (IF 20.3) Pub Date : 2024-04-26 Kanako Watanabe-Kusunoki, Chenyu Li, Tâmisa Seeko Bandeira Honda, Danyang Zhao, Yoshihiro Kusunoki, John Ku, Hao Long, Martin Klaus, Chao Han, Attila Braun, Elmina Mammadova-Bach, Andreas Linkermann, Kristof Van Avondt, Mathis Richter, Oliver Soehnlein, Monika I. Linder, Christoph Klein, Stefanie Steiger, Hans-Joachim Anders
Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein that serves as the final downstream effector of the pyroptosis/interleukin-1 beta (IL-1β) pathway, contributes to TMA and its consequences
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Correlation of immune fitness with response to teclistamab in relapsed/refractory multiple myeloma in the MajesTEC-1 study Blood (IF 20.3) Pub Date : 2024-04-26 Diana Cortes-Selva, Tatiana Perova, Sheri Skerget, Deeksha Vishwamitra, Sarah Stein, Rengasamy Boominathan, On Say Lau, Karl Nielsen, Cuc Davis, Jaymala Patel, Arnob Banerjee, Tara Stephenson, Clarissa Uhlar, Rachel Kobos, Jenna Goldberg, Lixia Pei, Danielle Trancucci, Suzette Girgis, Shun Xin Wang Lin, Liviawati S. Wu, Philippe Moreau, Saad Z. Usmani, Nizar J. Bahlis, Niels W. C. J. van de Donk, Raluca
Teclistamab, an off-the-shelf B-cell maturation antigen (BCMA) × CD3 bispecific antibody that mediates T-cell activation and subsequent lysis of BCMA-expressing myeloma cells, is approved for the treatment of patients with relapsed/refractory multiple myeloma (R/RMM). As a T-cell redirection therapy, clinical outcomes with teclistamab may be influenced by patient immune fitness and tumor antigen expression
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The ATF4-RPS19BP1 axis modulates ribosome biogenesis to promote erythropoiesis Blood (IF 20.3) Pub Date : 2024-04-26 Zhaofeng Zheng, Shangda Yang, Fanglin Gou, Chao Tang, Zhaoru Zhang, Quan Gu, Guohuan Sun, Penglei Jiang, Nini Wang, Xiangnan Zhao, Junnan Kang, Yifei Wang, Yicheng He, Meng Yang, Ting Lu, Shihong Lu, Pengxu Qian, Ping Zhu, Hui Cheng, Tao Cheng
Hematopoietic differentiation is controlled by intrinsic regulators and the extrinsic hematopoietic niche. Activating transcription factor 4 (ATF4) plays a crucial role in the function of fetal and adult hematopoietic stem cell maintenance. However, the precise function of ATF4 in the bone marrow (BM) niche and the mechanism by which ATF4 regulates adult hematopoiesis remain largely unknown. Here,
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How I treat Philadelphia chromosome–like acute lymphoblastic leukemia in children, adolescents, and young adults Blood (IF 20.3) Pub Date : 2024-04-26 Thai Hoa Tran, Sarah K. Tasian
Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) represents a high-risk B-lineage ALL subtype characterized by adverse clinical features and poor relapse-free survival despite risk–adapted multiagent chemotherapy regimens. The advent of next-generation sequencing has unraveled the diversity of kinase-activating genetic drivers in Ph-like ALL that are potentially amenable to personalized
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Current and upcoming treatment approaches to uncommon subtypes of PTCL (EATL, MEITL, SPTCL, and HSTCL) Blood (IF 20.3) Pub Date : 2024-04-26 Enrica Marchi, Jeffrey W. Craig, Matko Kalac
Rare subtypes of peripheral T-cell lymphoma (PTCL) including enteropathy–associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), subcutaneous panniculitis–like T-cell lymphoma (SPTCL), and hepatosplenic T-cell lymphoma (HSTCL) are underrepresented in most registries and clinical studies. Most of the literature is obtained from small case series, single-institution
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Efficacy of CAR T-cell therapy is not impaired by previous bispecific antibody treatment in large B-cell lymphoma Blood (IF 20.3) Pub Date : 2024-04-25 Gilles Crochet, Gloria Iacoboni, Audrey Couturier, Emmanuel Bachy, Josu Iraola-Truchuelo, Thomas Gastinne, Guillaume Cartron, Tom Fradon, Bastien Lesne, Mi Kwon, Romain Gounot, Nuria Martinez-Cibrian, Cristina Castilla-Llorente, Pau Abrisqueta, Manuel Guerreiro, Clementine Sarkozy, Jose Aspa-Cilleruelo, Vincent Camus, Stéphanie Guidez, Adrien Chauchet, Eric Deconinck, Krimo Bouabdallah, Francesc Bosch
In this retrospective study, chimeric antigen receptor T cells remained effective in patients with relapsed/refractory large B-cell lymphoma after prior exposure to bispecific antibodies (BsAbs) targeting different antigens. These results are relevant to clinical practice, particularly given the increasing use of BsAbs in earlier treatment lines.
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Procoagulant platelets promote immune evasion in triple-negative breast cancer Blood (IF 20.3) Pub Date : 2024-04-24 Johanna B. Schaubaecher, Bojan Smiljanov, Florian Haring, Katja Steiger, Zhengquan Wu, Joshua Luft, Simone Ballke, Shaan Mahameed, Vera Schneewind, Jonas Hildinger, Martin Canis, Laura A. Mittmann, Constanze Braun, Gabriele Zuchtriegel, Rainer Kaiser, Leo Nicolai, Matthias Mack, Wilko Weichert, Kirsten Lauber, Bernd Uhl, Christoph A. Reichel
Triple-negative breast cancer (TNBC) is an aggressive tumor entity in which immune checkpoint (IC) molecules are primarily synthesized in the tumor environment. Here, we report that procoagulant platelets bear large amounts of such immunomodulatory factors and that the presence of these cellular blood components in TNBC relates to protumorigenic immune-cell activity and impaired survival. Mechanistically
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Testing for t(3;8) in MYC/BCL6-rearranged large B-cell lymphoma identifies a high-risk subgroup with inferior survival Blood (IF 20.3) Pub Date : 2024-04-24 Bernard D. Maybury, Lisa James, Neil Phillips, Indrani Venkatadasari, Iman Qureshi, James Riley, Georgina Talbot, Shivir Moosai, Hannah Giles, Nicola Chadderton, James Dowds, Pallav Rakesh, Henry Crosland, Aidan Haslam, Sarah Lane, Monica Vega Gonzalez, David Davies, George Cherian, Amir Shenouda, Praveen Kaudlay, Jane Starczynski, Zbigniew Rudzki, Sridhar Chaganti
A reciprocal t(3;8) :: fusion is common in large B-cell lymphoma (LBCL) with and disruption. These pseudodouble hit cases are not adverse, whereas t(3;8) negative / lymphoma has an inferior prognosis relative to other MYC-rearranged LBCL.
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Ibrutinib as part of risk-stratified treatment for posttransplant lymphoproliferative disorder: the phase 2 TIDaL trial Blood (IF 20.3) Pub Date : 2024-04-23 Sridhar Chaganti, Shanna Maycock, Graham McIlroy, Aimee Jackson, Rebecca Bishop, Sarah Johnson, Edward Kanfer, Shireen Kassam, Kate Cwynarski, David Wrench, Arvind Arumainathan, Christopher P. Fox, Rod Johnson, Pam McKay, Shankara Paneesha, Clare Rowntree, Constantine Balotis, Graham P. Collins, Andrew Davies, Josh Wright, Sarah Burns, Arian Laurence, Keith Wheatley, Tobias Menne
Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm
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A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome Blood (IF 20.3) Pub Date : 2024-04-23 Raffaele Badolato, Laia Alsina, Antoine Azar, Yves Bertrand, Audrey A. Bolyard, David Dale, Angela Deyà-Martínez, Kathryn E. Dickerson, Navid Ezra, Henrik Hasle, Hyoung Jin Kang, Sorena Kiani-Alikhan, Taco W. Kuijpers, Alexander Kulagin, Daman Langguth, Carina Levin, Olaf Neth, Peter Olbrich, Jane Peake, Yulia Rodina, Caroline E. Rutten, Anna Shcherbina, Teresa K. Tarrant, Matthias G. Vossen, Christian
We investigated efficacy and safety of mavorixafor, an oral CXCR4 antagonist, for participants with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency caused by gain-of-function variants. This randomized (1:1), double-blind, placebo-controlled, phase 3 trial enrolled participants aged ≥12 years with WHIM syndrome and absolute neutrophil count (ANC)
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Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT Blood (IF 20.3) Pub Date : 2024-04-23 Juan Montoro, Dirk-Jan Eikema, Joe Tuffnell, Victoria Potter, Krzysztof Kalwak, Constantijn J. M. Halkes, Alexander Kulagin, Matthew Collin, Robert F. Wynn, Stephen Robinson, Emma Nicholson, Henrik Sengeloev, Jennifer Clay, Khalid Halahleh, Elena Skorobogatova, Jaime Sanz, Jakob Passweg, Stephan Mielke, Samppa Ryhänen, Ben Carpenter, Tobias Gedde-Dahl, Eleni Tholouli, Renato Fanin, Philippe Lewalle
Selecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in patients with SAA undergoing stem cell transplantation (SCT) from matched unrelated donors (MUD) (n = 1106), mismatched unrelated donors (MMUD) (n = 340), and haploidentical donors (Haplo) (n = 206) registered in the European Society
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Integrative single-cell chromatin and transcriptome analysis of human plasma cell differentiation Blood (IF 20.3) Pub Date : 2024-04-23 Elina Alaterre, Sara Ovejero, Caroline Bret, Laure Dutrieux, Dassou Sika, Raul Fernandez Perez, Marion Espéli, Thierry Fest, Michel Cogné, José Ignacio Martin-Subero, Pierre Milpied, Giacomo Cavalli, Jérôme Moreaux
Plasma cells (PCs) are highly specialized cells representing the end stage of B-cell differentiation. We have shown that PC differentiation can be reproduced in vitro using elaborate culture systems. The molecular changes occurring during PC differentiation are recapitulated in this in vitro differentiation model. However, a major challenge exists to decipher the spatiotemporal epigenetic and transcriptional
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Mitochondrial tRNA pseudouridylation governs erythropoiesis Blood (IF 20.3) Pub Date : 2024-04-23 Bichen Wang, Deyang Shi, Shuang Yang, Yu Lian, Haoyuan Li, Mutian Cao, Yifei He, Lele Zhang, Chen Qiu, Tong Liu, Wei Wen, Yuanwu Ma, Lei Shi, Tao Cheng, Lihong Shi, Weiping Yuan, Yajing Chu, Jun Shi
Pseudouridine is the most prevalent RNA modification, and its aberrant function is implicated in various human diseases. However, the specific impact of pseudouridylation on hematopoiesis remains poorly understood. Here, we investigated the role of transfer RNA (tRNA) pseudouridylation in erythropoiesis and its association with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia syndrome
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RAS/RAF landscape in monoclonal plasma cell conditions Blood (IF 20.3) Pub Date : 2024-04-23 Anais Schavgoulidze, Jill Corre, Mehmet Kemal Samur, Celine Mazzotti, Luka Pavageau, Aurore Perrot, Titouan Cazaubiel, Xavier Leleu, Margaret Macro, Karim Belhadj, Murielle Roussel, Sabine Brechignac, Lydia Montes, Denis Caillot, Laurent Frenzel, Philippe Rey, Jean-Marc Schiano de Colella, Thomas Chalopin, Caroline Jacquet, Valentine Richez, Frederique Orsini-Piocelle, Jean Fontan, Salomon Manier,
Multiple myeloma is characterized by a huge heterogeneity at the molecular level. The pathway is the most frequently mutated, in ∼50% of the patients. However, these mutations are frequently subclonal, suggesting a secondary event. Because these genes are part of our routine next-generation sequencing panel, we analyzed >10 000 patients with different plasma cell disorders to describe the landscape
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BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib Blood (IF 20.3) Pub Date : 2024-04-23 Ariel Leyte-Vidal, Diego Garrido Ruiz, RosaAnna DeFilippis, Inga B. Leske, Delphine Rea, Stacey Phan, Kaeli B. Miller, Feifei Hu, Anjeli Mase, Yibing Shan, Oliver Hantschel, Matthew P. Jacobson, Neil P. Shah
Secondary kinase domain mutations in BCR::ABL1 represent the most common cause of resistance to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia. The first 5 approved BCR::ABL1 TKIs target the adenosine triphosphate (ATP)–binding pocket. Mutations confer resistance to these ATP-competitive TKIs and those approved for other malignancies by decreasing TKI affinity and/or
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Cost-effectiveness of prophylaxis with recombinant vs plasma-derived VWF in severe von Willebrand disease in the United States Blood (IF 20.3) Pub Date : 2024-04-23 Christina Waldron, Satoko Ito, Daniel Wang, Cecily Allen, Giri Viswanathan, Robert D. Bona, Adam Cuker, George Goshua
We evaluated the cost-effectiveness of prophylaxis with recombinant von Willebrand factor (rVWF) vs with plasma-derived von Willebrand factor (pdVWF) for patients with severe Von Willebrand disease. We found that rVWF is a cost-saving factor replacement compared with pdVWF across all willingness-to-pay thresholds in the United States.
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Deletion of mouse lysyl oxidase in megakaryocytes affects bone properties in a sex-dependent manner Blood (IF 20.3) Pub Date : 2024-04-23 Aikaterini Karagianni, Anastasia Iris Karkempetzaki, Daniel Brooks, Shinobu Matsuura, Vrinda Dambal, Philip C. Trackman, Katya Ravid
Lysyl oxidase (LOX) is a facilitator of extracellular matrix cross-linking. Using newly developed megakaryocyte-specific LOX knockout mice, we show that LOX expressed in these scarce bone marrow cells affects bone volume and collagen architecture in a sex-dependent manner.
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Antibody-drug conjugate adverse effects can be understood and addressed based on immune complex clearance mechanisms Blood (IF 20.3) Pub Date : 2024-04-22 Ronald P. Taylor, Margaret A. Lindorfer
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Primary large B-cell lymphomas of immune-privileged sites Blood (IF 20.3) Pub Date : 2024-04-22 Mark Roschewski, James D. Phelan, Elaine S. Jaffe
Diffuse large B-cell lymphoma (DLBCL) encompasses a diverse spectrum of aggressive B-cell lymphomas with remarkable genetic heterogeneity and myriad clinical presentations. Multiplatform genomic analyses of DLBCL have identified oncogenic drivers within genetic subtypes that allow for pathologic subclassification of tumors into discrete entities with shared immunophenotypic, genetic, and clinical features
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Standardized indolent systemic mastocytosis evaluations across a health care system: implications for screening accuracy Blood (IF 20.3) Pub Date : 2024-04-22 Jeremy C. McMurray, Curtis S. Pacheco, Brandon J. Schornack, Xiaoping Sun, Janet A. Brunader, Alexis E. Scott, Juan S. Ariza, Chung Ting J. Kou, Ryan C. Costantino, Luke M. Pittman, Karla E. Adams, Aubri M. Waters, Eric M. Pryor, Jonathan J. Lyons, Dean D. Metcalfe, Irina Maric, Nathan A. Boggs
Timely diagnosis of systemic mastocytosis (SM) remains challenging because of care heterogeneity. We implemented a standardized approach for SM screening and diagnosis using a novel health care system–wide international screening registry. A retrospective analysis assessed rates of SM, cutaneous mastocytosis (CM), and molecular diagnoses before and 2 years after care standardization. The accuracy of
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Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity Blood (IF 20.3) Pub Date : 2024-04-22 Frederick L. Locke, Tanya Siddiqi, Caron A. Jacobson, Armin Ghobadi, Sairah Ahmed, David B. Miklos, Miguel-Angel Perales, Javier Munoz, Warren B. Fingrut, Martina Pennisi, Jordan Gauthier, Mazyar Shadman, Lohith Gowda, Abu-Sayeef Mirza, Muhammad Bilal Abid, Sanghee Hong, Navneet S. Majhail, Mohamed A. Kharfan-Dabaja, Arushi Khurana, Talha Badar, Yi Lin, N. Nora Bennani, Megan M. Herr, Zhen-Huan Hu
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor T-cell therapy approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting the use of axi-cel for patients with LBCL, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race
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Human herpesvirus 6 reactivation and disease are infrequent in chimeric antigen receptor T-cell therapy recipients Blood (IF 20.3) Pub Date : 2024-04-22 Eleftheria Kampouri, Elizabeth M. Krantz, Hu Xie, Sarah S. Ibrahimi, Erika S. Kiem, Mandeep K. Sekhon, Emily C. Liang, Andrew J. Cowan, Andrew Portuguese, Damian J. Green, Aya Albittar, Jennifer J. Huang, Jordan Gauthier, Ailyn C. Pérez-Osorio, Keith R. Jerome, Danielle M. Zerr, Michael J. Boeckh, Joshua A. Hill
Human herpesvirus 6B (HHV-6B) reactivation and disease are increasingly reported after chimeric antigen receptor (CAR) T-cell therapy (CARTx). HHV-6 reactivation in the CAR T-cell product was recently reported, raising questions about product and patient management. Because of overlapping manifestations with immune effector cell–associated neurotoxicity syndrome, diagnosing HHV-6B encephalitis is challenging
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Fitusiran reduces bleeding in factor X–deficient mice Blood (IF 20.3) Pub Date : 2024-04-18 Sebastien Verhenne, Geneviève McCluskey, Hortense Maynadié, Frédéric Adam, Caterina Casari, Laurence Panicot-Dubois, Lydie Crescence, Christophe Dubois, Cécile V. Denis, Peter J. Lenting, Olivier D. Christophe
Factor X (FX) deficiency is a rare bleeding disorder manifesting a bleeding tendency caused by low FX activity levels. We aim to explore the use of fitusiran (an investigational small interfering RNA that silences antithrombin expression) to increase thrombin generation and the in vivo hemostatic potential under conditions of FX deficiency. We therefore developed a novel model of inducible FX deficiency
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Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies Blood (IF 20.3) Pub Date : 2024-04-16 Petra Langerbeins, Adam Giza, Sandra Robrecht, Paula Cramer, Julia von Tresckow, Othman Al-Sawaf, Anna Maria Fink, Moritz Fürstenau, Nadine Kutsch, Florian Simon, Valentin Goede, Manuela Hoechstetter, Carsten Utoft Niemann, Caspar da Cunha-Bang, Arnon Kater, Julie Dubois, Michael Gregor, Philipp Bernhard Staber, Eugen Tausch, Christof Schneider, Stephan Stilgenbauer, Barbara Eichhorst, Kirsten Fischer
We evaluated the chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) in patients with CLL treated first line with targeted drugs (n = 991) or chemoimmunotherapy (n = 1256). With a median observation time of 40.5 months, the 3-year progression-free survival (PFS) rates for targeted drug–treated patients varied by CLL-IPI risk group: 96.5% (low), 87.6% (intermediate), 82.4% (high),
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Acalabrutinib, venetoclax, and obinutuzumab in relapsed/refractory CLL: final efficacy and ctDNA analysis of the CLL2-BAAG trial Blood (IF 20.3) Pub Date : 2024-04-16 Moritz Fürstenau, Adam Giza, Jonathan Weiss, Fanni Kleinert, Sandra Robrecht, Fabian Franzen, Janina Stumpf, Petra Langerbeins, Othman Al-Sawaf, Florian Simon, Anna-Maria Fink, Christof Schneider, Eugen Tausch, Johannes Schetelig, Peter Dreger, Sebastian Böttcher, Kirsten Fischer, Karl-Anton Kreuzer, Matthias Ritgen, Anke Schilhabel, Monika Brüggemann, Stephan Stilgenbauer, Barbara Eichhorst, Michael
The phase 2 CLL2-BAAG trial tested the measurable residual disease (MRD)–guided triple combination of acalabrutinib, venetoclax, and obinutuzumab after optional bendamustine debulking in 45 patients with relapsed/refractory chronic lymphocytic leukemia (CLL). MRD was measured by flow cytometry (FCM; undetectable MRD <10) in peripheral blood (PB) and circulating tumor DNA (ctDNA) using digital droplet
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SOX11 expression is restricted to EBV-negative Burkitt lymphoma and is associated with molecular genetic features Blood (IF 20.3) Pub Date : 2024-04-16 Marta Sureda-Gómez, Ingram Iaccarino, Anna De Bolòs, Mieke Meyer, Patricia Balsas, Julia Richter, Marta-Leonor Rodríguez, Cristina López, Maria Carreras-Caballé, Selina Glaser, Ferran Nadeu, Pedro Jares, Guillem Clot, Maria Chiara Siciliano, Cristiana Bellan, Salvatore Tornambè, Roberto Boccacci, Lorenzo Leoncini, Elias Campo, Reiner Siebert, Virginia Amador, Wolfram Klapper
SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to BL pathogenesis remains uncertain. Here, we observed that the presence of Epstein-Barr virus (EBV) and
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GM-CSF receptor expression determines opposing innate memory phenotypes at different stages of myelopoiesis Blood (IF 20.3) Pub Date : 2024-04-16 Paula Guerrero, Cristina Bono, María Sobén, Andrea Guiu, Quen J. Cheng, M. Luisa Gil, Alberto Yáñez
Inflammatory responses must be tightly coordinated with the activation of emergency myelopoiesis to produce potent myeloid cells that fight infection without causing excessive host damage. Here, we show that granulocyte-macrophage colony stimulating factor (GM-CSF) programs myeloid-committed progenitors to produce trained macrophages (increased cytokine response), but programs the upstream noncommitted
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Notch1 regulates hepatic thrombopoietin production Blood (IF 20.3) Pub Date : 2024-04-16 Yueyue Sun, Huan Tong, Xiang Chu, Yingying Li, Jie Zhang, Yangyang Ding, Sixuan Zhang, Xiang Gui, Chong Chen, Mengdi Xu, Zhenyu Li, Elizabeth E. Gardiner, Robert K. Andrews, Lingyu Zeng, Kailin Xu, Jianlin Qiao
Notch signaling regulates cell-fate decisions in several developmental processes and cell functions. However, the role of Notch in hepatic thrombopoietin (TPO) production remains unclear. We noted thrombocytopenia in mice with hepatic deficiency and so investigated TPO production and other features of platelets in these mice. We found that the liver ultrastructure and hepatocyte function were comparable
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What clinicians should know about surrogate end points in hematologic malignancies Blood (IF 20.3) Pub Date : 2024-04-15 Côme Bommier, Matthew John Maurer, Jerome Lambert
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Variation in mesenchymal KITL/SCF and IGF1 expression in middle age underlies steady-state hematopoietic stem cell aging Blood (IF 20.3) Pub Date : 2024-04-12 Kira A. Young, Maria A. Telpoukhovskaia, Johanna Hofmann, Jayna J. Mistry, Konstantinos D. Kokkaliaris, Jennifer J. Trowbridge
Intrinsic molecular programs and extrinsic factors including proinflammatory molecules are understood to regulate hematopoietic aging. This is based on foundational studies using genetic perturbation to evaluate causality. However, individual organisms exhibit natural variation in the hematopoietic aging phenotypes and the molecular basis of this heterogeneity is poorly understood. Here, we generated
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NSD2 drives t(4;14) myeloma cell dependence on adenylate kinase 2 by diverting one-carbon metabolism to the epigenome Blood (IF 20.3) Pub Date : 2024-04-12 Amin Sobh, Elena Encinas, Alisha Patel, Greeshma Surapaneni, Emilie Bonilla, Charlotte Kaestner, Janai Poullard, Monica Clerio, Karthik Vasan, Tzipporah Freeman, Dongwen Lv, Daphné Dupéré-Richér, Alberto Riva, Benjamin G. Barwick, Daohong Zhou, Lawrence H. Boise, Constantine S. Mitsiades, Baek Kim, Richard L. Bennett, Navdeep S. Chandel, Jonathan D. Licht
Chromosomal translocation (4;14), an adverse prognostic factor in multiple myeloma (MM), drives overexpression of the histone methyltransferase NSD2. A genome-wide CRISPR screen in MM cells identified adenylate kinase 2 (AK2), an enzyme critical for high-energy phosphate transfer from the mitochondria, as an NSD2-driven vulnerability. AK2 suppression in t(4;14) MM cells decreased reduced NADP (NADP[H])
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Reduction of mortality, cardiac damage, and cerebral damage by IL-1 inhibition in a murine model of TTP Blood (IF 20.3) Pub Date : 2024-04-10 Romain Muller, Raphaël Cauchois, Marie Lagarde, Sandrine Roffino, Cécile Genovesio, Samantha Fernandez, Guillaume Hache, Benjamin Guillet, Yéter Kara, Marion Marlinge, Peter Lenting, Pascale Poullin, Françoise Dignat-George, Edwige Tellier, Gilles Kaplanski
Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in von Willebrand factor cleavage resulting in capillary microthrombus formation and ischemic organ damage. Interleukin-1 (IL-1) has been shown to drive sterile inflammation after ischemia and could play an essential contribution to postischemic organ damage in TTP. Our objectives were to evaluate
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Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma Blood (IF 20.3) Pub Date : 2024-04-09 Emma Kroeze, Ingram Iaccarino, Michelle M. Kleisman, Mayukh Mondal, Thomas Beder, Mouhamad Khouja, Marc P. Höppner, Marijn A. Scheijde-Vermeulen, Lennart A. Kester, Monika Brüggemann, Claudia D. Baldus, Gunnar Cario, Reno S. Bladergroen, Nathalie Garnier, Andishe Attarbaschi, Jaime Verdu-Amorós, Rosemary Sutton, Elizabeth Macintyre, Kenneth Scholten, Laura Arias Padilla, Birgit Burkhardt, Auke Beishuizen
Pediatric B-cell precursor (BCP) lymphoblastic malignancies are neoplasms with manifestation either in the bone marrow or blood (BCP acute lymphoblastic leukemia [BCP-ALL]) or are less common in extramedullary tissue (BCP lymphoblastic lymphoma [BCP-LBL]). Although both presentations are similar in morphology and immunophenotype, molecular studies have been virtually restricted to BCP-ALL so far. The
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Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival Blood (IF 20.3) Pub Date : 2024-04-08 Tanja C. Vallée, Jannik S. Glasmacher, Hannes Buchner, Peter D. Arkwright, Uta Behrends, Anastasia Bondarenko, Michael J. Browning, David Buchbinder, Alessandro Cattoni, Liudmyla Chernyshova, Peter Ciznar, Theresa Cole, Wojciech Czogała, Gregor Dueckers, John David M. Edgar, Fatih Erbey, Anders Fasth, Francesca Ferrua, Renata Formankova, Eleonora Gambineri, Andrew R. Gennery, Frederick D. Goldman,
Wiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a variant from 26 countries
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IL-18-secreting multiantigen targeting CAR T cells eliminate antigen-low myeloma in an immunocompetent mouse model Blood (IF 20.3) Pub Date : 2024-04-08 Brandon D. Ng, Adhithi Rajagopalan, Anastasia I. Kousa, Jacob S. Fischman, Sophia Chen, Alyssa Massa, Harold K. Elias, Dylan Manuele, Michael Galiano, Andri L. Lemarquis, Alexander P. Boardman, Susan DeWolf, Jonah Pierce, Bjarne Bogen, Scott E. James, Marcel R. M. van den Brink
Multiple myeloma is a plasma cell malignancy that is currently incurable with conventional therapies. Following the success of CD19-targeted chimeric antigen receptor (CAR) T cells in leukemia and lymphoma, CAR T cells targeting B-cell maturation antigen (BCMA) more recently demonstrated impressive activity in relapsed and refractory myeloma patients. However, BCMA-directed therapy can fail due to
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Loss of the stress sensor GADD45A promotes stem cell activity and ferroptosis resistance in LGR4/HOXA9-dependent AML Blood (IF 20.3) Pub Date : 2024-04-08 Nunki Hassan, Hangyu Yi, Bilal Malik, Lucie Gaspard-Boulinc, Saumya E. Samaraweera, Debora A. Casolari, Janith Seneviratne, Anushree Balachandran, Tracy Chew, Alastair Duly, Daniel R. Carter, Belamy B. Cheung, Murray Norris, Michelle Haber, Maria Kavallaris, Glenn M. Marshall, Xu Dong Zhang, Tao Liu, Jianlong Wang, Dan A. Liebermann, Richard J. D’Andrea, Jenny Y. Wang
The overall prognosis of acute myeloid leukemia (AML) remains dismal, largely because of the inability of current therapies to kill leukemia stem cells (LSCs) with intrinsic resistance. Loss of the stress sensor GADD45A is implicated in poor clinical outcomes, but its role in LSCs and AML pathogenesis is unknown. Here, we define GADD45A as a key downstream target of LGR4 oncogenic signaling and discover
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Bone marrow niches for hematopoietic stem cells: life span dynamics and adaptation to acute stress Blood (IF 20.3) Pub Date : 2024-04-08 Johanna Hofmann, Konstantinos D. Kokkaliaris
Hematopoietic stem cells (HSCs) are instrumental for organismal survival because they are responsible for lifelong production of mature blood lineages in homeostasis and response to external stress. To fulfill their function, HSCs rely on reciprocal interactions with specialized tissue microenvironments, termed HSC niches. From embryonic development to advanced aging, HSCs transition through several
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Platelet-derived TGF-β1 induces functional reprogramming of myeloid–derived suppressor cells in immune thrombocytopenia Blood (IF 20.3) Pub Date : 2024-04-06 Lingjun Wang, Haoyi Wang, Mingfang Zhu, Xiaofei Ni, Lu Sun, Wanru Wang, Jie Xie, Yubin Li, Yitong Xu, Ruting Wang, Shouqing Han, Ping Zhang, Jun Peng, Ming Hou, Yu Hou
Platelet α-granules are rich in transforming growth factor β1 (TGF-β1), which is associated with myeloid–derived suppressor cell (MDSC) biology. Responders to thrombopoietin receptor agonists (TPO-RAs) revealed a parallel increase in the number of both platelets and MDSCs. Here, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to establish an active
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A way to “mimic” the pathophysiology of acquired SAA Blood (IF 20.3) Pub Date : 2024-04-04 Amy E. DeZern
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Soft tick relapsing fever in a traveler returning from Colorado Blood (IF 20.3) Pub Date : 2024-04-04 Jill Schuett, Eduard Matkovic
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A treatment bridge for infants with hemophilia Blood (IF 20.3) Pub Date : 2024-04-04 Thomas C. Abshire
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Uncovering new layers of Ph+ ALL biology Blood (IF 20.3) Pub Date : 2024-04-04 Rathana Kim, Emmanuelle Clappier
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An evolving understanding of low VWF and type 1 VWD Blood (IF 20.3) Pub Date : 2024-04-04 Nathan T. Connell
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Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume Blood (IF 20.3) Pub Date : 2024-04-03 Frederick L. Locke, Olalekan O. Oluwole, John Kuruvilla, Catherine Thieblemont, Franck Morschhauser, Gilles Salles, Steven P. Rowe, Saran Vardhanabhuti, Joshua Winters, Simone Filosto, Christina To, Paul Cheng, Marco Schupp, Ronald Korn, Marie José Kersten
Metabolic tumor volume (MTV) assessed using 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography, a measure of tumor burden, is a promising prognostic indicator in large B-cell lymphoma (LBCL). This exploratory analysis evaluated relationships between baseline MTV (categorized as low [median or less] vs high [greater than median]) and clinical outcomes in the phase 3 ZUMA-7 study (NCT03391466)
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B-cell–directed CAR T-cell therapy activates CD8+ cytotoxic CARneg bystander T cells in patients and nonhuman primates Blood (IF 20.3) Pub Date : 2024-04-03 James Kaminski, Ryan A. Fleming, Francesca Alvarez-Calderon, Marlana B. Winschel, Connor McGuckin, Emily E. Ho, Fay Eng, Xianliang Rui, Paula Keskula, Lorenzo Cagnin, Joanne Charles, Jillian Zavistaski, Steven P. Margossian, Malika A. Kapadia, James B. Rottman, Jennifer Lane, Susanne H. C. Baumeister, Victor Tkachev, Alex K. Shalek, Leslie S. Kean, Ulrike Gerdemann
Chimeric antigen receptor (CAR) T cells hold promise as a therapy for B-cell–derived malignancies, and despite their impressive initial response rates, a significant proportion of patients ultimately experience relapse. Although recent studies have explored the mechanisms of in vivo CAR T-cell function, little is understood about the activation of surrounding CAR bystander T cells and their potential