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2. Large Deletion in the Factor VIII Gene Is a Predictor of Immune Tolerance Induction Failure in People with Severe and Moderately-Severe Hemophilia a and High-Responding Inhibitors

Author

Zuccherato, Luciana W., Souza, Renan P., Camelo, Ricardo M., Dias, Maise M., Santana, Marcio A. P., Jardim, Letícia L., Oliveira, Andrea G., Lorenzato, Claudia S., Cerqueira, Monica H., Franco, Vivian K. B., Ribeiro, Rosangela A., Etto, Leina Y., Roberti, Maria R. F., Callado, Fábia M. R. A., Cerqueira, Maria A. F., Pinto, Ieda S. S., Garcia, Andrea A., Anegawa, Tânia H., Neves, Daniele C. F., Tan, Doralice M., Chaves, Daniel G., and Rezende, Suely M.

Published
2023
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3. Incidence, Clinical Associations, and Co-Mutation Patterns of UBA1 Mutations in MDS

Author

Sirenko, Maria, Bernard, Elsa, Beck, David B., Creignou, Maria, Domenico, Dylan, Farina, Andrea, Arango, Juan E, Kosmider, Olivier, Hasserjian, Robert P., Jadersten, Martin, Germing, Ulrich, Sanz, Guillermo, van de Loosdrecht, Arjan A., Follo, Matilde Y, Thol, Felicitas R., Zamora, Lurdes, Pinheiro, Ronald Feitosa, Pellagatti, Andrea, Elias, Harold K., Haase, Detlef, Ganster, Christina, Ades, Lionel, Tobiasson, Magnus, Palomo, Laura, Della Porta, Matteo G., Huberman, Kety, Fenaux, Pierre, Belickova, Monika, Savona, Michael R., Klimek, Virginia M., Santos, Fabio Pires de Souza, Boultwood, Jacqueline, Kotsianidis, Ioannis, Santini, Valeria, Solé, Francesc, Platzbecker, Uwe, Heuser, Michael, Valent, Peter, Finelli, Carlo, Voso, Maria Teresa, Shih, Lee-Yung, Ogawa, Seishi, Fontenay, Michaela, Jansen, Joop H., Cervera, Jose, Ebert, Benjamin L., Bejar, Rafael, Greenberg, Peter L, Gattermann, Norbert, Malcovati, Luca, Cazzola, Mario, Hellström-Lindberg, Eva, and Papaemmanuil, Elli

Published
2022
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4. Gasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formation

Author

Silva, Camila Meirelles S., Wanderley, Carlos Wagner S., Veras, Flavio P., Sonego, Fabiane, Nascimento, Daniele C., Gonçalves, Augusto V., Martins, Timna V., Cólon, David F., Borges, Vanessa F., Brauer, Verônica S., Damasceno, Luis Eduardo A., Silva, Katiussia P., Toller-Kawahisa, Juliana E., Batah, Sabrina S., Souza, Ana Letícia J., Monteiro, Valter S., Oliveira, Antônio Edson R., Donate, Paula B., Zoppi, Daniel, Borges, Marcos C., Almeida, Fausto, Nakaya, Helder I., Fabro, Alexandre T., Cunha, Thiago M., Alves-Filho, José Carlos, Zamboni, Dario S., and Cunha, Fernando Q.

Abstract

Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment.

Published
2021
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5. ALLG AMLM26 Phase 1B/2 Study Investigating Novel Therapies to Target Early Relapse and Clonal Evolution As Pre-Emptive Therapy in AML (INTERCEPT): A Multi-Arm, Precision-Based, Recursive, Platform Trial

Author

Wei, Andrew H, Iland, Harry J, Reynolds, John, Loo, Sun, Chua, Chong Chyn, Westerman, David, Tiong, Ing S, Ivey, Adam, Blombery, Piers, Anstee, Natasha S, Koldej, Rachel M, Curtis, David J., Kipp, David, Ritchie, David, Ross, David M, Souza, Amanda, Collins, Jenny, Bajel, Ashish, Grove, Carolyn, Marlton, Paula, Roberts, Andrew W, Pemmaraju, Naveen, Patel, Keyur P., Loghavi, Sanam, Konopleva, Marina, Daver, Naval, and DiNardo, Courtney D.

Published
2022
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6. Survival Outcomes for High Risk Primary Refractory and Relapsed Large B-Cell Lymphoma (LBCL) within the Veterans Health Administration (VHA)

Author

Boyle, Lauren Diaz, Kaur, Supreet, Roman Souza, Gabriel, Ananth, Snegha, Lucero, Kana Tai, Al-Abayechi, Alaq, Blaize, Jean Pierre, Djoufack Djoumessi, Lakene Raissa, Espinoza, Manuel, Franklin, Kathleen, Lu, Lindsey, Nazarewicz, Phillip, Pandya, Abhishek, Song, Michael M., Warnecke, Brian, Whitehead, Jennifer, Williams, Madison H., Williams, Ryan A., Mader, Michael, and Nooruddin, Zohra

Published
2022
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9. Treatment Patterns and Survival Outcomes in Elderly Veterans Diagnosed with Diffuse Large B-Cell Lymphoma

Author

Ananth, Snegha, Kaur, Supreet, Al-Abayechi, Alaq, Blaize, Jean Pierre, Boyle, Lauren Diaz, Djoufack Djoumessi, Lakene Raissa, Espinoza Gutarra, Manuel, Franklin, Kathleen, Lu, Lindsey, Lucero, Kana Tai, Nazarewicz, Phillip, Pandya, Abhishek, Roman Souza, Gabriel, Song, Michael M., Warnecke, Brian, Whitehead, Jennifer, Williams, Madison H., Williams, Ryan A., Mader, Michael, and Nooruddin, Zohra

Published
2022
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10. CD38 deletion of human primary NK cells eliminates daratumumab-induced fratricide and boosts their effector activity

Author

Naeimi Kararoudi, Meisam, Nagai, Yuya, Elmas, Ezgi, de Souza Fernandes Pereira, Marcelo, Ali, Syed Abbas, Imus, Philip Hollingsworth, Wethington, Darren, Borrello, Ivan Marques, Lee, Dean Anthony, and Ghiaur, Gabriel

Abstract

Multiple myeloma (MM) is a plasma cell neoplasm that commonly expresses CD38. Daratumumab (DARA), a human monoclonal antibody targeting CD38, has significantly improved the outcome of patients with relapsed or refractory MM, but the response is transient in most cases. Putative mechanisms of suboptimal efficacy of DARA include downregulation of CD38 expression and overexpression of complement inhibitory proteins on MM target cells as well as DARA-induced depletion of CD38high natural killer (NK) cells resulting in crippled antibody-dependent cellular cytotoxicity (ADCC). Here, we tested whether maintaining NK cell function during DARA therapy could maximize DARA-mediated ADCC against MM cells and deepen the response. We used the CRISPR/Cas9 system to delete CD38 (CD38KO) in ex vivo expanded peripheral blood NK cells. These CD38KO NK cells were completely resistant to DARA-induced fratricide, showed superior persistence in immune-deficient mice pretreated with DARA, and enhanced ADCC activity against CD38-expressing MM cell lines and primary MM cells. In addition, transcriptomic and cellular metabolic analysis demonstrated that CD38KO NK cells have unique metabolic reprogramming with higher mitochondrial respiratory capacity. Finally, we evaluated the impact of exposure to all-trans retinoic acid (ATRA) on wild-type NK and CD38KO NK cell function and highlighted potential benefits and drawbacks of combining ATRA with DARA in patients with MM. Taken together, these findings provide proof of concept that adoptive immunotherapy using ex vivo expanded CD38KO NK cells has the potential to boost DARA activity in MM.

Published
2020
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11. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19

Author

Hottz, Eugenio D., Azevedo-Quintanilha, Isaclaudia G., Palhinha, Lohanna, Teixeira, Lívia, Barreto, Ester A., Pão, Camila R. R., Righy, Cassia, Franco, Sérgio, Souza, Thiago M. L., Kurtz, Pedro, Bozza, Fernando A., and Bozza, Patrícia T.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent pathogen responsible for the coronavirus disease 2019 (COVID-19). Since its emergence, the novel coronavirus has rapidly achieved pandemic proportions causing remarkably increased morbidity and mortality around the world. A hypercoagulability state has been reported as a major pathologic event in COVID-19, and thromboembolic complications listed among life-threatening complications of the disease. Platelets are chief effector cells of hemostasis and pathological thrombosis. However, the participation of platelets in the pathogenesis of COVID-19 remains elusive. This report demonstrates that increased platelet activation and platelet-monocyte aggregate formation are observed in severe COVID-19 patients, but not in patients presenting mild COVID-19 syndrome. In addition, exposure to plasma from severe COVID-19 patients increased the activation of control platelets ex vivo. In our cohort of COVID-19 patients admitted to the intensive care unit, platelet-monocyte interaction was strongly associated with tissue factor (TF) expression by the monocytes. Platelet activation and monocyte TF expression were associated with markers of coagulation exacerbation as fibrinogen and D-dimers, and were increased in patients requiring invasive mechanical ventilation or patients who evolved with in-hospital mortality. Finally, platelets from severe COVID-19 patients were able to induce TF expression ex vivo in monocytes from healthy volunteers, a phenomenon that was inhibited by platelet P-selectin neutralization or integrin αIIb/β3 blocking with the aggregation inhibitor abciximab. Altogether, these data shed light on new pathological mechanisms involving platelet activation and platelet-dependent monocyte TF expression, which were associated with COVID-19 severity and mortality.

Published
2020
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12. A fully human anti-BMP6 antibody reduces the need for erythropoietin in rodent models of the anemia of chronic disease

Author

Petzer, Verena, Tymoszuk, Piotr, Asshoff, Malte, Carvalho, Joana, Papworth, Jonathan, Deantonio, Cecilia, Bayliss, Luke, Wake, Matthew Stephen, Seifert, Markus, Brigo, Natascha, Valente de Souza, Lara, Hilbe, Richard, Grubwieser, Philipp, Demetz, Egon, Dichtl, Stefanie, Volani, Chiara, Berger, Sylvia, Böhm, Felix, Hoffmann, Alexander, Pfeifhofer-Obermair, Christa, von Raffay, Laura, Sopper, Sieghart, Arndt, Stephanie, Bosserhoff, Anja, Kautz, Léon, Perrier, Prunelle, Nairz, Manfred, Wolf, Dominik, Weiss, Guenter, Germaschewski, Volker, and Theurl, Igor

Abstract

Recombinant erythropoietin (EPO) and iron substitution are a standard of care for treatment of anemias associated with chronic inflammation, including anemia of chronic kidney disease. A black box warning for EPO therapy and concerns about negative side effects related to high-dose iron supplementation as well as the significant proportion of patients becoming EPO resistant over time explains the medical need to define novel strategies to ameliorate anemia of chronic disease (ACD). As hepcidin is central to the iron-restrictive phenotype in ACD, therapeutic approaches targeting hepcidin were recently developed. We herein report the therapeutic effects of a fully human anti-BMP6 antibody (KY1070) either as monotherapy or in combination with Darbepoetin alfa on iron metabolism and anemia resolution in 2 different, well-established, and clinically relevant rodent models of ACD. In addition to counteracting hepcidin-driven iron limitation for erythropoiesis, we found that the combination of KY1070 and recombinant human EPO improved the erythroid response compared with either monotherapy in a qualitative and quantitative manner. Consequently, the combination of KY1070 and Darbepoetin alfa resulted in an EPO-sparing effect. Moreover, we found that suppression of hepcidin via KY1070 modulates ferroportin expression on erythroid precursor cells, thereby lowering potentially toxic-free intracellular iron levels and by accelerating erythroid output as reflected by increased maturation of erythrocyte progenitors. In summary, we conclude that treatment of ACD, as a highly complex disease, becomes more effective by a multifactorial therapeutic approach upon mobilization of endogenous iron deposits and stimulation of erythropoiesis.

Published
2020
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13. Brazilian Non-Hodgkin T Cell Registry: An Exploratory Analysis of Extranodal Sites

Author

Fischer, Thais, Miranda, Eliana C M CM, Castro, Nelson, Pereira, Juliana, Borducchi, Davimar Miranda Maciel, Medina, Samuel de S, Brasil, Sergio Augusto B, De Farias, Danielle Leao Cordeiro, Bellesso, Marcelo, Tavarez, Jamila Vaz, Cecyn, Karin Z, Schaffel, Rony, Nabhan, Samir, Nogueira, Frederico Lisboa, Baptista, Renata, Barroso, Fernando, Souza, Renata R, Dal Pont, Mateus Dalló, Vilarim, Carolina Colaço, Macedo, Claudio G, Cunha, Ademar Dantas, Giacon, Patricia, Negreiros, Elizete, Hamerschlak, Nelson, Figueiredo, Vera, Cle, Diego Vila, Zing, Natalia Pin Chuen, Dias, Maria Almeida, Gaiolla, Rafael, Gonzaga, Yung Bruno, Souto Filho, Joao Tadeu Damian, Ribeiro, Eduardo F O, Silva, Gilnara Fontinele, Mo, Suellen Ka Gi, Perini, Guilherme F, Matedi, Milena, Hallack Neto, Abrahão Elias, Rabelo, Yana S, Federico, Massimo, Souza, Carmino A, and Chiattone, Carlos

Abstract

Introduction:T cell lymphomas (NHL-T) account for 10-15% of all non-Hodgkin lymphomas (NHL). They are a heterogeneous group of infrequent neoplasms with a variable clinical course but prevalently aggressive behavior and high mortality rates. Diagnosis is still challenging and there has been little change in the overall prognosis over the last two decades. In spite of IPI (International Prognostic Index) that include extranodal (EN) site in its variables, lack is known regarding EN involvement in nodal peripheral T cell lymphomas- PTCL (PTCL-NOS, TFH and ALCL ALK+/ALK-) location or impact on prognosis).

Published
2023
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14. Five-Year Follow-up of the Phase I/II Discontinuation Trial of Imatinib after Pioglitazone (EDI-PIO) in Chronic Myeloid Leukemia Patients in Deep Molecular Response

Author

Pagnano, Katia B, Lopes, Ana Beatriz Pascoal, Miranda, Eliana C M Cristina Martins, Delamain, Marcia, Duarte, Gislaine B O, Medina, Samuel de Souza, Pericole, Fernando Vieira, Amarante, Guilherme Brasil Duffles, Duarte, Bruno K, Pavan, Graziele, Toni, Isabella Macedo, De Paula, Erich V, and Souza, Carmino Antonio

Published
2022
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16. Expression of CD38 and Zap-70 Antigens in Chronic Lymphocytic Leukemia

Author

Theodoro, Flavio Cristine Medeiros, Silva, Giovani Arlindo, Oliveira, Taissa Moura, Lima, Rafael Duarte, Araújo, Maria das Graças Pereira, Silveira, Lenilton Silva, Soares, Victor lima, Gonçalves, Ciro Alexandre Mercês, Dantas, Arthur Felipe Araujo, Oliveira, Gustavo Henrique de Medeiros, Silva, Dany Geraldo Kramer Cavalcanti, Paiva, Hugo Diogenes De Oliveira, Diogenes, Catarina Silva de Souza, Diogenes, Aline Abreu, Souza, Maria Jacqueline Nogueira, Paiva, Aldair Sousa, and Cavalcanti, Geraldo Barroso

Published
2022
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17. Differences in Characteristics and Outcomes of Central Nervous System Versus Systemic Relapse after First Line Therapy in DLBCL Patients: A Veterans Health Administration (VHA) Study

Author

Horowitz, Amy M, Nooruddin, Zohra, Mader, Michael, Franklin, Kathleen, Williams, Madison, Williams, Ryan, Blaize, Jean-Pierre, Ananth, Snegha, Song, Michael Meansup, Warnecke, Brian, Pandya, Abhishek, Djoufack Djoumessi, Lakene Raissa, Lu, Lindsey, Nazarewicz, Phillip, Espinoza-Gutarra, Manuel, Lucero, Kana Tai, Whitehead, Jennifer, Al-Abayechi, Alaq, Boyle, Lauren, Lee, Sophia, Roman Souza, Gabriel, Naqvi, Amna, Toro Velez, Esteban, Mines, Ian, and Kaur, Supreet

Abstract

Introduction

Published
2023
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18. Survival Outcomes of Diffuse Large B Cell Lymphoma Beyond the Rituximab Era: Comprehensive Analysis of a Veteran Population within the Veterans Health Administration over 11 Years

Author

Lee, Sophia, Kaur, Supreet, Mader, Michael, Franklin, Kathleen, Williams, Madison, Williams, Ryan, Blaize, Jean-Pierre, Naqvi, Amna, Ananth, Snegha, Song, Michael Meansup, Warnecke, Brian, Pandya, Abhishek, Djoufack Djoumessi, Lakene Raissa, Lu, Lindsey, Nazarewicz, Phillip, Espinoza-Gutarra, Manuel, Lucero, Kana Tai, Whitehead, Jennifer, Al-Abayechi, Alaq, Boyle, Lauren, Roman Souza, Gabriel, Toro Velez, Esteban, Mines, Ian, and Nooruddin, Zohra

Abstract

Introduction: The standard treatment approach for DLBCL has traditionally relied on chemo-immunotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) for decades. However, approximately 30-40%, remain refractory or experience relapse with poor outcomes. Since 2017, the landscape for relapsed refractory DLBCL has changed dramatically with the FDA approval of newer monoclonal antibody, chimeric antigen receptor (CAR) T-cell, antibody-drug conjugate, and bispecific T-cell engagers. Nonetheless, a comprehensive analysis of population survival outcomes since the new treatment modalities remains to be evaluated. In this study, we present an extensive demographic analysis of one of the largest DLBCL cohort to date within the VHA, spanning over 11 years, and the survival outcomes before and after 2017 period. By assessing this vast dataset, we aim to provide valuable insights into the changing landscape of DLBCL treatment and its impact on patient survival.

Published
2023
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19. Predictive Value of BCR::ABL1Transcripts Kinetics in the Molecular Relapse of Chronic Myeloid Leukemia Patients after Tyrosine Kinase Inhibitors Discontinuation: Results from the DES-CML Study

Author

Murbach, Bruna A, Oliveira, Gislaine Borba, Palma, Leonardo Carvalho, Miranda, Eliana C M CM, Amarante, Guilherme D, Furlin, Graziele CP, Toni, Isabella Macedo, De Souza, Carmino, Figueiredo-Pontes, Lorena, and Pagnano, Katia B

Abstract

Duration of previous treatment, duration and depth of molecular response, previous resistance, BCR::ABL1transcript, and lymphocyte subtypes are known predictive factors of molecular recurrence after tyrosine kinase inhibitors (TKI) discontinuation in chronic myeloid leukemia (CML) patients (pts). Few studies explored the kinetics of BCR::ABL1during a dose de-escalation phase before discontinuation in predicting molecular relapse.

Published
2023
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20. CD38 KO/CD38-CAR Human Primary Natural Killer Cells Enhance Cytotoxicity Against CD38-Expressing Primary Lymphoma, Leukemia, and Myeloma

Author

Troy, Ella C, Sezgin, Yasemin, Pereira, Marcelo De Souza, Caporale, Joseph, Behbehani, Gregory K, Lyberger, Justin, Lee, Dean Anthony, and Naeimi Kararoudi, Meisam

Abstract

Natural killer (NK) cells have strong cancer immunotherapeutic potential that can be further augmented by engineering with a chimeric antigen receptor (CAR). CD38, a transmembrane glycoprotein involved in signal transduction and cellular adhesion, is highly expressed on the surface of the hematologic malignancies multiple myeloma (MM), acute myeloid leukemia (AML), Burkitt Lymphoma (BL) and T-cell acute lymphoblastic leukemia (T-ALL). FDA approved CD38 monoclonal antibodies (mAb) daratumumab and isatuximab are used to treat MM in patients, and have been tested to treat other CD38 expressing malignancies. NK cells play an imperative role in the efficacy of these antibodies and have natural antitumor activity against these cancers. However, because NK cells also highly express CD38, anti-CD38 mAb can cause NK cell fratricide, limiting their efficacy.

Published
2023
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21. Reclassification of Ascertain (ASTX727-02) Myelodysplastic Syndrome (MDS) Patients: Outcomes Including Clinical Response, Overall Survival (OS), and Leukemia Free Survival (LFS) Based on IPSS-R and IPSS-M Scoring Systems

Author

Garcia-Manero, Guillermo, McCloskey, James, Griffiths, Elizabeth A., Zeidan, Amer M., Yee, Karen W.L., Al-Kali, Aref, Deeg, H. Joachim, Patel, Prapti A., Sabloff, Mitchell, Keating, Mary-Margaret, Zhu, Nancy, Gabrail, Nashat Y., Fazal, Salman, Maly, Joseph J., Odenike, Olatoyosi, Kantarjian, Hagop M., DeZern, Amy E., O'Connell, Casey L., Roboz, Gail J., Busque, Lambert, Buckstein, Rena, Amin, Harsh, Randhawa, Jasleen K., Leber, Brian, Lee, Shannon, Chan, Winny, Souza, Sonia, Sano, Yuri, Keer, Harold N., and Savona, Michael R.

Abstract

Background:

Published
2023
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22. Examining Racial Disparities in Diffuse Large B-Cell Lymphoma (DLBCL) Outcomes within the Veterans Health Administration (VHA)

Author

Ta, Andrew, Kaur, Supreet, Mader, Michael, Franklin, Kathleen, Williams, Madison, Williams, Ryan, Blaize, Jean-Pierre, Naqvi, Amna, Ananth, Snegha, Song, Michael Meansup, Warnecke, Brian, Pandya, Abhishek, Djoufack Djoumessi, Lakene Raissa, Nazarewicz, Phillip, Espinoza-Gutarra, Manuel, Lucero, Kana Tai, Whitehead, Jennifer, Al-Abayechi, Alaq, Boyle, Lauren, Lee, Sophia, Roman Souza, Gabriel, Toro Velez, Esteban, Mines, Ian, and Nooruddin, Zohra

Abstract

INTRODUCTION:

Published
2023
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23. Epidemiology, Clinical Features and Outcomes of Peripheral T-Cell Lymphoma in Latin America

Author

Fischer, Thais, Idrobo, Henry, Pavlovsky, Astrid, Castro, Denisse, Beltran, Brady, Enriquez, Daniel J, Vasquez, Jule F, Roche, Claudia, Artiles, Daniel, Valvert, Fabiola, Villela, Luis Mario, Pereira, Juliana, Oliver, Carolina, Tavarez, Jamila Vaz, Brasil, Sergio Augusto B, Cecyn, Karin Z, Castro, Nelson, Baptista, Renata, Medina, Samuel de S, Borducchi, Davimar Miranda Maciel, Bellesso, Marcelo, De Farias, Danielle Leao Cordeiro, Gonzaga, Yung Bruno, Warley, Fernando, Fiad, Lorena, Korin, Laura, Pereyra, Patricio Hernan, Peña, Camila, Torres, Maria Alejandra, Mahuad, Carolina Valeria, Von Glasenapp, Alana, Quiroz, Alfredo Reinaldo, Gazitua, Raimundo, Samanez-Figari, Cesar Augusto, Sardu, Lautaro, Arriola, Juan Pablo, Isnardi, Sebastian, Maradei, Juan L., Gabus, Raul Hector, Enrico, Alicia I., Guanchiale, Luciana A, Arangueren, Florencia Negri, Altuve, Juan Ignacio García, Cerutti, Amalia, Penalva, Romina, Trucco, Jose Ignacio Garcia, Pessolani, Florencia, Gilli, Virginia, Diaz, Joaquin, Martinez, Maria Enriqueta, Jarchum, Gustavo, Perinotto, Gabriela Celia, Barraza, Teresa, Ciarlo, Sergio, Rojas, Christine, Rios Jiménez, Rosa Oliday, De Souza, Carmino, Manni, Martina, Miranda, Eliana C M CM, Federico, Massimo, Valcarcel, Bryan, Chiattone, Carlos, and Malpica Castillo, Luis Enrique

Abstract

INTRODUCTION: Peripheral T-cell lymphomas (PTCL) represent a rare and heterogenous group of mature T-cell lymphomas often characterized by aggressive behavior. Previous studies evaluating the distribution of PTCL subtypes across Latin America (LATAM) were limited in their representation of most countries in the region. Additionally, a lack of standardized management for several subtypes and the absence of comprehensive lymphoma registries in LATAM suggests exploring real-world treatment patterns and clinical outcomes. We conducted an international pooled analysis to assess the distribution of PTCL across LATAM countries and report treatment outcomes.

Published
2023
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25. Retrospective Analysis of Treatment Patterns and Outcomes in Geriatric Patients with Diffuse Large B-Cell Lymphoma (DLBCL) in the Veterans Health Administration (VHA)

Author

Latiolais, Heidi, Kaur, Supreet, Mader, Michael, Franklin, Kathleen, Williams, Madison, Williams, Ryan, Blaize, Jean-Pierre, Naqvi, Amna, Ananth, Snegha, Song, Michael Meansup, Warnecke, Brian, Pandya, Abhishek, Djoufack Djoumessi, Lakene Raissa, Lu, Lindsey, Nazarewicz, Phillip, Espinoza-Gutarra, Manuel, Lucero, Kana Tai, Whitehead, Jennifer, Al-Abayechi, Alaq, Boyle, Lauren, Lee, Sophia, Roman Souza, Gabriel, Toro Velez, Esteban, Mines, Ian, and Nooruddin, Zohra

Abstract

Introduction

Published
2023
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26. The Proteomic Signature of Extracellular Vesicles from Sickle Cell Anemia Patients Provides Insights into Their Possible Role in the Pathophysiology of the Disease

Author

de Souza, Cristiane Maria, Yokoo, Sami, Lima Camargo, Ana Carolina, Ramos Domingues, Romenia, Lanaro, Carolina, Dorigatti Borges, Marina, Sesti-Costa, Renata, Saad, Sara Teresinha Olalla, Franco Paes Leme, Adriana, and Costa, Fernando Ferreira

Abstract

Sickle cell anemia (SCA) is marked by hemolysis and vaso-occlusion, which contribute to various other complications observed in the disease. Extracellular vesicles (EVs), released by activated cells, serve as carriers of various markers, proteins, and RNA derived from their parent cells. These structures have the ability to transfer their cargo to the recipient cells, modulating their activity. Despite EVs involvement in physiological processes, there is growing evidence of their role in certain blood diseases, making them a subject of extensive research in recent years.

Published
2023
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27. Final Report: Somatic Mutations and HMGCLL1 Haplotype Are Not Associated with Molecular Relapse-Free Survival in Patients with Chronic Myeloid Leukemia Who Attempt Treatment-Free Remission

Author

Perusini, Maria Agustina, Pagnano, Katia, Pavlovsky, Carolina, Moiraghi, Beatriz, Varela, Ana, Bianchini, Michele, Fava, Carmen, Mayer, Jiří, Žáčková, Daniela, Kvetková, Anežka, Jurček, Tomáš, Ježíšková, Ivana, Lopes, Ana Beatriz Pascoal, Oliveira, Gislaine Borba, De Souza, Carmino, Ambalavanan, Amirthagowri, Travas, Anthea, Kim, Jaeyoon John, Pyne, Danielle, Medeiros, Jessie, Abelson, Sagi, and Kim, Dennis Dong Hwan

Abstract

Background

Published
2023
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30. A Landscape of Dendritic Cells Development, Activation and Migration in Mouse Model of Sickle Cell Anemia

Author

Souza, Matheus Ajeje, Paes, Izabela Felice, Saad, Sara Teresinha Olalla, Costa, Fernando Ferreira, and Sesti-Costa, Renata

Abstract

Dendritic cells (DCs) are crucial players of innate immunity in initiating, polarizing, and regulating the adaptive immune response. They become activated upon encountering either pathogen- or damage-associated molecular patterns (PAMPs or DAMPs), which are often released due to tissue necrosis or intravascular hemolysis, common events in individuals with sickle cell disease (SCD), one of the most common hemoglobinophaties that affects millions of people worldwide. Upon activation, DCs migrate to peripheral lymph nodes, where they present antigens to T lymphocyte together with co-stimulatory or inhibitory molecules. In addition, they can polarize T cell response by releasing pro- or anti-inflammatory cytokines. We previously showed that SCD patients have higher circulating total and inflammatory DCs, whereas the ratio of type 1 conventional DCs (cDC1) is lower than control individuals. These changes correlated with number of reticulocytes and with the skewed T response towards Th17. Alterations in the development and activation of DC subpopulations, as well as in their function can impair the immune response or tolerance, which may account for the dysfunction in T lymphocyte responses observed in SCD patients.

Published
2023
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31. External Validation of the Advanced-Stage Hodgkin Lymphoma International Prognostic Index (A-HIPI): Strong Calibration in the Brazilian Prospective Hodgkin Lymphoma Registry

Author

Biasoli, Irene, Buccheri, Valeria, Moreira, Frederico Rafael, Castro, Nelson, Vilarim, Carolina Colaço, Traina, Fabiola, Chiattone, Carlos, Praxedes, Monica, Solza, Cristiana, Perobelli, Leila, Baiocchi, Otavio, Gaiolla, Rafael, Boquimpani, Carla, Sola, Caroline Bonamin, Silva, Roberta Oliveira P, Ribas, Ana Carolina, Pagnano, Katia, Steffenello, Giovanna, De Souza, Carmino, Spector, Nelson, Rodday, Angie Mae, Upshaw, Jenica, Maurer, Matthew J., Evens, Andrew M, and Parsons, Susan K

Abstract

Background:To be useful across the broadest range of patients and clinical settings, clinical prediction models should be externally validated in different data sets and clinical settings and refined over time. In 2022, the HoLISTIC Consortium (www.hodgkinconsortium.org) developed and validated the A-HIPI model via TRIPOD guidelines for adults 18-65 with advanced stage classic Hodgkin Lymphoma (AS-HL) (Rodday et al., JCO2023). The A-HIPI model, based on individual patient (pt) data from more than 5000 patients (pts) from North America, Europe, and Australia, predicts progression-free survival and overall survival within the first 5 years (PFS5 and OS5) based on pre-treatment pt and disease characteristics (www.qxmd.com/calculate/calculator_869/a-hipi). In collaboration with Brazilian clinical experts and researchers, we describe the performance of the A-HIPI in the Brazilian Prospective HL registry.

Published
2023
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32. Tyrosine Kinase Inhibitor Withdrawal Syndrome in Chronic Myeloid Leukemia Patients Participants of Two Discontinuation Clinical Trials

Author

Murbach, Bruna A, Guidini, Victor H, Palma, Leonardo Carvalho, Miranda, Eliana C M CM, Oliveira, Gislaine Borba, Amarante, Guilherme D, Furlin, Graziele CP, Toni, Isabella Macedo, De Souza, Carmino, Pontes, Lorena Figueiredo-, and Pagnano, Katia B

Abstract

Discontinuation of tyrosine kinase inhibitors (TKI) is currently one of the main goals in CML treatment. One of the known adverse events after TKI discontinuation is withdrawal syndrome (WS), which can occur in about 30% of patients (pts), characterized by musculoskeletal pain that begins or worsens weeks after interruption and may be more severe in some cases, but rarely leading to the need for TKI reintroduction. Some studies suggest TKI dose reduction or optimization before stopping treatment may reduce WS rates.

Published
2023
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33. Real-World Applications of Guideline Based Diagnostic and Treatment Patterns for Diffuse Large B-Cell Lymphoma within the Veterans Health Administration (VHA)

Author

Naqvi, Amna, Kaur, Supreet, Mader, Michael, Franklin, Kathleen, Williams, Madison, Williams, Ryan, Blaize, Jean-Pierre, Ananth, Snegha, Song, Michael Meansup, Warnecke, Brian, Pandya, Abhishek, Djoufack Djoumessi, Lakene Raissa, Lu, Lindsey, Nazarewicz, Phillip, Espinoza-Gutarra, Manuel, Lucero, Kana Tai, Whitehead, Jennifer, Al-Abayechi, Alaq, Boyle, Lauren, Lee, Sophia, Roman Souza, Gabriel, Toro Velez, Esteban, Mines, Ian, and Nooruddin, Zohra

Abstract

High grade lymphomas, with MYC and BCL2 and/or BCL6 rearrangements (HGL) occur in less than 10% of DLBCL. While clinical trials demonstrated poor outcomes following standard rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) therapy for HGL since the early 2000s, the World Health Organization (WHO) identified this as a new category in 2016. There was a lack of consensus for FISH testing until NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®) (V.1.2020) moved Karyotype/FISH testing for MYC from “USEFUL UNDER CERTAIN CIRCUMSTANCES” to “ESSENTIAL”. NCCN Guidelines ® V.1.2018 recognizes the lack of standard of care for HGL and comments about using dose-adjusted (DA) R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) DA-EPOCH-R for this category. The VHA is the largest integrated, uniform care access system in the United States. The objective of this study is to understand the real-world applications of NCCN Guidelines on testing and treatment patterns in DLBCL within VHA.

Published
2023
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34. Real World Evidence- the Proportion of Myeloma Patients' Death Due to Early Progression

Author

Crusoe, Edvan de Queiroz, Ribeiro, Glaciano, Perobelli, Leila, Zanella, Karla, Souza, Emanuella Graciott, Centrone, Renato, Higashi, Fabiana, Bittencourt, Rosane, Moreno, Fabio, Saraiva, Joao, Magalhaes Filho, Roberto Pessoa, Moura, Fernanda Lemos, Cantadori, Lucas Oliveira, Maciel, James, Sola, Caroline Bonamin, Hallack Neto, Abrahão Elias, Ovigli Silva Lopes, Danielle C., Araujo, Cleder Aparecido Da Silva Da Silva, Braga, Walter Moisés Tobias, Herriot, Luciana Barreto, Gusmao, Breno, Martinez, Gracia, Soares, Luiza, Vaz, Jorge, Maiolino, Angelo, and Hungria, Vania T.M

Abstract

Introduction: Real-world (RW) studies provide valuable insights and complimentary data that may not be covered by clinical trials. In general, RW studies customarily collect data retrospectively, but it is important to have prospective RW studies that can contribute in a better way to reduce possible bias and qualify information. Besides that, RW data fully represent patients followed in a routine

Published
2023
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36. Clinical Significance of Flow Cytometry Findings in Brazilian Patients with De Novo Acute Myeloid Leukemia

Author

Morais, Linduarte Varela, Lima, Rafael Duarte, Gil, Erica Aires, Paiva, Aldair Sousa, Silveira, Lenilton Silva, Soares, Victor lima, Gonçalves, Ciro Alexandre Mercês, Oliveira, Taissa Moura, Oliveira, Gustavo Henrique de Medeiros, Silva, Dany Geraldo Kramer Cavalcanti, Paiva, Hugo Diogenes De Oliveira, Souza, Maria Jacqueline Nogueira, Diogenes, Aline Abreu, Diogenes, Catarina Silva de Souza, and Cavalcanti, Geraldo Barroso

Published
2022
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37. Characterization of the Immunophenotypical Profile By Flow Cytometry of Patients with Adult T-Cell Leukemia/Lymphoma

Author

Silva, Giovani Arlindo, Theodoro, Flavio Cristine Medeiros, Oliveira, Taissa Moura, Lima, Rafael Duarte, Araújo, Maria das Graças Pereira, Silveira, Lenilton Silva, Soares, Victor lima, Gonçalves, Ciro Alexandre Mercês, Dantas, Arthur Felipe Araujo, Oliveira, Gustavo Henrique de Medeiros, Oliveira, Gustavo Henrique de Medeiros, Silva, Dany Geraldo Kramer Cavalcanti, Paiva, Aldair Sousa, Paiva, Hugo Diogenes De Oliveira, Diogenes, Catarina Silva de Souza, Diogenes, Aline Abreu, Souza, Maria Jacqueline Nogueira, and Cavalcanti, Geraldo Barroso

Published
2022
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39. The Prognostic Impact of HMGCLL1 Gene Variant on Treatment Outcomes in Chronic Myeloid Leukemia (CML) Patients: Adverse Impact on the Response, Failure, and Progression with Imatinib Which Can be Abrogated By the Use of 2nd Generation Tyrosine Kinase Inhibitor (TKI) Upfront Therapy

Author

Perusini, Maria Agustina, Kim, Taehyung Simon, Žácková, Daniela, Pagnano, Katia B, Mayer, Jiří, Pavlovsky, Carolina, Ježíšková, Ivana, Kvetková, Anežka, Jurček, Tomáš, Moiraghi, Beatriz, Varela, Ana Ines, Bianchini, Michele, Lopes, Ana Beatriz Pascoal, Duarte, Gislaine B O, Yoo, Young Seok, Souza, Carmino Antonio, Medeiros, Jessie, Lee, Hye Won, Kim, Kyoung Ha, Yi, Seong Yoon, Chang, Myung Hee, Abelson, Sagi, and Kim, Dennis Dong Hwan

Published
2022
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43. Evaluation of Anti-PF4 Positivity and Platelet Activation after COVID-19 Vaccination with Ad26.COV2.S in Brazil

Author

Bokel, Joanna, Mendes-de-Almeida, Daniela P., Martins-Gonçalves, Remy, Grinsztejn, Eduarda, Hoagland, Brenda, Wagner, Sandra, Geraldo, Kim Mattos, Coutinho, Sandro Nazer, Georg, Ingebourg, Oliveira de Mello, Maria Helena, Souza, Flávia dos Santos, Vizzoni, Alexandre G., Veloso, Valdiléa, Bozza, Patrícia T., and Grinsztejn, Beatriz

Published
2022
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44. Somatic Mutations Are Frequently Detected in CML Patients before Treatment-Free Remission (TFR) Attempt with Tyrosine Kinase Inhibitor (TKI) Discontinuation but with Uncertain Predictive Value for Tfr Failure

Author

Perusini, Maria Agustina, Pagnano, Katia B, Pavlovsky, Carolina, Moiraghi, Beatriz, Varela, Ana Ines, Bianchini, Michele, Mayer, Jiří, Žácková, Daniela, Kvetková, Anežka, Jurček, Tomáš, Ježíšková, Ivana, Lopes, Ana Beatriz Pascoal, Duarte, Gislaine B O, Souza, Carmino Antonio, Medeiros, Jessie J.F., Kim, Taehyung Simon, Yoo, Young Seok, Kim, Kyoung Ha, Lee, Hye Won, Chang, Myung Hee, Yi, Seong Yoon, Abelson, Sagi, and Kim, Dennis

Published
2022
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47. A Phase 1-2, Open-Label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Activity of Tolinapant in Combination with Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Subjects with Relapsed/Refractory Peripheral T-Cell Lymphoma

Author

Shortt, Jake, Poligone, Brian, Ribrag, Vincent, Zinzani, Pier Luigi, El-Sharkawi, Dima, Walewski, Jan, Prica, Anca, Wilson, Laksmi, Souza, Sonia, Keer, Harold N., Taylor, Jason A., and Marchi, Enrica

Published
2022
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48. The Impact of Time from Diagnosis to Initiation of Chemotherapy on Survival of Patients with Diffuse Large B-Cell Lymphoma in the Veteran`s Health Administration

Author

Roman Souza, Gabriel, Kaur, Supreet, Boyle, Lauren Diaz, Ananth, Snegha, Lucero, Kana Tai, Al-Abayechi, Alaq, Blaize, Jean Pierre, Djoufack Djoumessi, Lakene Raissa, Espinoza Gutarra, Manuel, Franklin, Kathleen, Lu, Lindsey, Nazarewicz, Phillip, Pandya, Abhishek, Song, Michael M., Warnecke, Brian, Whitehead, Jennifer, Williams, Madison H., Williams, Ryan A., Mader, Michael, and Nooruddin, Zohra

Published
2022
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49. Daratumumab (Dara), Cyclophosphamide, Thalidomide and Dexamethasone for Transplant Eligible Newly Diagnosed Multiple Myeloma (TE NDMM) Patients: Response Rate Impacts on PFS

Author

De Queiroz Crusoe, Edvan, Leal, Joanna, Santos, Juliana Andrade, Santos, Herbert Henrique de Melo, Santos, Allan de souza, Lucas, Larissa Ferreira, Almeida, Alessandro de M., Chaves, Marcos, Dutra, Daniela Dourado, Hungria, Vania T.M., Salvino, Marco Aurelio, and Arruda, Maria da Gloria B.

Published
2022
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50. The Prognostic Impact of HMGCLL1Gene Variant on Treatment Outcomes in Chronic Myeloid Leukemia (CML) Patients: Adverse Impact on the Response, Failure, and Progression with Imatinib Which Can be Abrogated By the Use of 2ndGeneration Tyrosine Kinase Inhibitor (TKI) Upfront Therapy

Author

Perusini, Maria Agustina, Kim, Taehyung Simon, Žácková, Daniela, Pagnano, Katia B, Mayer, Jiří, Pavlovsky, Carolina, Ježíšková, Ivana, Kvetková, Anežka, Jurček, Tomáš, Moiraghi, Beatriz, Varela, Ana Ines, Bianchini, Michele, Lopes, Ana Beatriz Pascoal, Duarte, Gislaine B O, Yoo, Young Seok, Souza, Carmino Antonio, Medeiros, Jessie, Lee, Hye Won, Kim, Kyoung Ha, Yi, Seong Yoon, Chang, Myung Hee, Abelson, Sagi, and Kim, Dennis Dong Hwan

Published
2022
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