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Juanjuan Zhao, Yongping Song, Delong Liu
The current treatment for pediatric acute lymphoblastic leukemia (ALL) is highly successful with high cure rate. However, the treatment of adult ALL remains a challenge, particularly for refractory and/or relapsed (R/R) ALL. The advent of new targeted agents, blinatumomab, inotuzumab ozogamycin, and chimeric antigen receptor (CAR) T cells, are changing the treatment paradigm for ALL. Tisagenlecleucel (kymriah, Novartis) is an autologous CD19-targeted CAR T cell product approved for treatment of R/R B cell ALL and lymphoma...
February 14, 2019: Journal of Hematology & Oncology
Ibrahim Aldoss, Stephen J Forman, Vinod Pullarkat
Acute lymphoblastic leukemia (ALL) in older adults presents a real challenge as a result of adverse disease biology and comorbidities that preclude delivering curative regimens. Conventional chemotherapy approaches have generally yielded unsatisfactory results in older patients with ALL as a result of excessive induction mortality, chemotherapy resistance of the leukemia, and the need to omit or dose reduce key drugs during the course of therapy because of adverse effects. Philadelphia chromosome-positive ALL represents about a quarter of newly diagnosed older adults, and the striking single-agent activity and excellent safety profile of tyrosine kinase inhibitors has allowed incorporation of these agents into therapy, significantly improving the outcome of older adults with Philadelphia chromosome-positive ALL...
February 2019: Journal of Oncology Practice
Ma Michelle D Peñaranda, Ingvill Jensen, Linn G Tollersrud, Jack-Ansgar Bruun, Jorunn B Jørgensen
Fish immunology research is at a pivotal point with the increasing availability of functional immunoassays and major advances in omics approaches. However, studies on fish B cells and their distinct subsets remain a challenge due to the limited availability of differentially expressed surface markers. To address this constraint, cell surface proteome of Atlantic salmon IgM+ B cells were analyzed by mass spectrometry and compared to surface proteins detected from two adherent salmon head kidney cell lines, ASK and SSP-9...
2019: Frontiers in Immunology
Noelia Dasilva-Freire, Andrea Mayado, Cristina Teodosio, María Jara-Acevedo, Iván Álvarez-Twose, Almudena Matito, Laura Sánchez-Muñoz, Carolina Caldas, Ana Henriques, Javier I Muñoz-González, Andrés C García-Montero, J Ignacio Sánchez-Gallego, Luis Escribano, Alberto Orfao
Despite recent therapeutic advances, systemic mastocytosis (SM) remains an incurable disease due to limited complete remission (CR) rates even after novel therapies. To date, no study has evaluated the expression on SM bone marrow mast cells (BMMC) of large panel of cell surface suitable for antibody-targeted therapy. In this study, we analyzed the expression profile of six cell-surface proteins for which antibody-based therapies are available, on BMMC from 166 SM patients vs. 40 controls. Overall, variable patterns of expression for the markers evaluated were observed among SM BMMC...
January 28, 2019: International Journal of Molecular Sciences
Gwang Hun Jeong, Keum Hwa Lee, I Re Lee, Ji Hyun Oh, Dong Wook Kim, Jae Won Shin, Andreas Kronbichler, Michael Eisenhut, Hans J van der Vliet, Omar Abdel-Rahman, Brendon Stubbs, Marco Solmi, Nicola Veronese, Elena Dragioti, Ai Koyanagi, Joaquim Radua, Jae Il Shin
Capillary leak syndrome (CLS) is a rare disease with profound vascular leakage, which can be associated with a high mortality. There have been several reports on CLS as an adverse effect of anti-cancer agents and therapy, but the incidence of CLS according to the kinds of anti-cancer drugs has not been systemically evaluated. Thus, the aim of our study was to comprehensively meta-analyze the incidence of CLS by different types of cancer treatment or after bone marrow transplantation (BMT). We searched the literatures (inception to July 2018) and among 4612 articles, 62 clinical trials (studies) were eligible...
January 26, 2019: Journal of Clinical Medicine
Elias Jabbour, Anjali S Advani, Matthias Stelljes, Wendy Stock, Michaela Liedtke, Nicola Gökbuget, Giovanni Martinelli, Susan O'Brien, Jane Liang White, Tao Wang, M Luisa Paccagnella, Barbara Sleight, Erik Vandendries, Daniel J DeAngelo, Hagop M Kantarjian
Karyotype is frequently used to predict response and outcome in leukemia. This post hoc exploratory analysis evaluated the relationship between baseline cytogenetics and outcome in patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) treated with inotuzumab ozogamicin (InO), a humanized CD22 antibody conjugated to calicheamicin, in the phase 3, open-label, randomized INO-VATE trial. Data as of March 8, 2016, are presented in this analysis. Of the 326 patients randomized, 284 had screening karyotyping data (144 in the InO arm and 140 in the standard care [SC] arm)...
January 8, 2019: American Journal of Hematology
Joseph Wynne, David Wright, Wendy Stock
Inotuzumab ozogamicin (InO) is a recently US Food and Drug Administration-approved antibody-drug conjugate for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). InO consists of a CD22-targeting immunoglobulin G4 humanized monoclonal antibody conjugated to calicheamicin. Although initially developed for the treatment of non-Hodgkin lymphoma (NHL) because of activity in preclinical models and high response rates in indolent lymphomas, a phase 3 trial was negative and further development focused on CD22+ ALL...
January 8, 2019: Blood Advances
Tonglin Hu, Jianping Shen, Wenbin Liu, Zhiying Zheng
RATIONALE: Acute lymphoblastic leukemia (ALL) secondary to multiple myeloma (MM) is rare. Here we report a rare case of secondary ALL transformed from MM. PATIENT CONCERNS: A 64-year-old woman was diagnosed as MM IgG light chain type in 2001. She achieved complete remission after 2 cycles of therapy, and received maintenance therapy with thalidomide. The patient suffered from MM relapse in September 2011. Bone marrow examination showed that the percentage of primary lymphocytes was 59%, indicating ALL-L2 (Pre-B-ALL)...
January 2019: Medicine (Baltimore)
Mohammad Javad Keikhai Farzaneh, Shahrokh Nasseri, Mehdi Momennezhad, Roham Salek
Background: Deep inspiration breath-hold (DIBH) is known as a radiotherapy method for the treatment of patients with left-sided breast cancer. In this method, patient is under exposure only while he/she is at the end of a deep inspiration cycle and holds his/her breath. In this situation, the volume of the lung tissue is enhanced and the heart tissue is pushed away from the treating breast. Therefore, heart dose of these patients, using DIBH, experiences a considerable decline compared to free breathing treatment...
October 2018: Journal of Medical Signals and Sensors
Muhammad Rahil Khan, Arsalan Ahmad, Naila Kayani, Khurram Minhas
Background: B-cell malignancies including Precursor B-cell lymphoblastic lymphoma/leukemia and Hodgkin Lymphoma show a wide spectrum of B-cell differentiation from early stage B-cell precursors to mature B-cells ending in terminal differentiation to plasma cells. Pan-B-cell antigens routinely used for the diagnosis of B-cell lymphoma, include CD19, CD20, CD22 and CD79a.PAX-5 protein, also known as B-cell-specific activation protein is a B-cell-specific transcription factor; essential for commitment and functional maintenance used in the diagnosis of B cell Hodgkin and non-Hodgkin lymphoma...
December 25, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Haiying Qin, Sneha Ramakrishna, Sang Nguyen, Thomas J Fountaine, Anusha Ponduri, Maryalice Stetler-Stevenson, Constance M Yuan, Waleed Haso, Jack F Shern, Nirali N Shah, Terry J Fry
Despite high remission rates following CAR-T cell therapy in B-ALL, relapse due to loss of the targeted antigen is increasingly recognized as a mechanism of immune escape. We hypothesized that simultaneous targeting of CD19 and CD22 may reduce the likelihood of antigen loss, thus improving sustained remission rates. A systematic approach to the generation of CAR constructs incorporating two target-binding domains led to several novel CD19/CD22 bivalent CAR constructs. Importantly, we demonstrate the challenges associated with the construction of a bivalent CAR format that preserves bifunctionality against both CD19 and CD22...
December 21, 2018: Molecular Therapy Oncolytics
Mohamed K Al-Essa, Susanne Melzer, Attila Tárnok
Red blood cells (RBCs) are attractive tools for surface modification to adhere specifically to molecules, cellular fragments (e.g., microvesicles), or whole cells for potential use in bioanalytical assays or as a delivery vehicle in targeted therapy. Within this study, we have loaded RBCs with fluorochrome-conjugated antibodies (Ab) against CD45 and CD22 leukocyte markers and evaluated the conjugation process by microscopy. We have assessed the potential application of RBCs fragments generated from conjugated RBCs for targeting Cyto-Trol control cells by flow cytometric (FCM) approaches...
December 21, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Frederick Lansigan, Ian Barak, Brandelyn Pitcher, Sin-Ho Jung, Bruce D Cheson, Myron Czuczman, Peter Martin, Eric Hsi, Heiko Schöder, Scott Smith, Nancy L Bartlett, John P Leonard, Kristie A Blum
Follicular lymphoma (FL) patients treated with firstline R-CHOP who experience progression of disease (POD) within 2 years have a shorter survival than those who do not have POD within 2 years. Whether this observation holds for patients treated initially with biologic immunotherapy alone is unknown. We performed a retrospective analysis of 174 patients pooled from three frontline rituximab (R)-based nonchemotherapy doublet trials: R-galiximab (Anti-CD80, CALGB 50402), R-epratuzumab (Anti-CD22, CALGB 50701), and R-lenalidomide (CALGB 50803) to determine outcomes of early progressors and risk factors for early POD, defined as progression within 24 months from study entry...
January 2019: Cancer Medicine
Sarah J Meyer, Alexandra T Linder, Carolin Brandl, Lars Nitschke
CD22 and Siglec-G are members of the Siglec family. Both are inhibitory co-receptors on the surface of B cells and inhibit B-cell receptor induced signaling, characterized by inhibition of the calcium mobilization and cellular activation. CD22 functions predominantly as an inhibitor on conventional B cells, while Siglec-G is an important inhibitor on the B1a-cell subset. These two B-cell Siglecs do not only inhibit initial signaling, but also have an important function in preventing autoimmunity, as double deficient mice develop a lupus-like phenotype with age...
2018: Frontiers in Immunology
Kifayat Ullah, Frank Addai Peprah, Feng Yu, Haifeng Shi
Adoptive cell transfer (ACT) is an emerging immunotherapy technique that restricts tumor growth and invasion in cancer patients. Among the different types of ACT, chimeric antigen receptor (CAR)T‑cell therapy is considered to be the most advanced and a potentially powerful technique for the treatment of cancer in clinical trials. The primary aim of CART‑cell therapy is to destroy cancer cells and therefore, it serves an important role in tumor immunotherapy. CART‑cell therapy has been demonstrated to mainly treat blood cancer by targeting cluster of differentiation (CD)‑19, CD20, CD22, CD33 and CD123...
December 2018: Oncology Reports
Khairul Syahputra, Per W Kania, Azmi Al-Jubury, Rzgar M Jafaar, Ron P Dirks, Kurt Buchmann
The parasite Ichthyophthirius multifiliis infecting skin, fins and gills of a wide range of freshwater fish species, including rainbow trout, is known to induce a protective immune response in the host. Although a number of studies have reported activation of several immune genes in infected fish host, the immune response picture is still considered incomplete. In order to address this issue, a comparative transcriptomic analysis was performed on infected versus uninfected rainbow trout gills and it showed that a total of 3352 (7...
December 1, 2018: Fish & Shellfish Immunology
Tania Jain, Mark R Litzow
Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in >80% of patients if associated with multiorgan failure...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Shira Dinner, Michaela Liedtke
The use of multiagent combination chemotherapy regimens results in cure rates of >90% for children and ∼40% for adults with acute lymphoblastic leukemia (ALL) but is associated with extensive toxicity and disappointingly low efficacy in relapsed patients. ALL blast cells express several surface antigens, including CD20, CD22, and CD19, which represent valuable targets for immunotherapy. Monoclonal antibodies, antibody-drug conjugates, and bispecific T-cell-engaging antibodies targeting these antigens offer novel mechanisms of action...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Tania Jain, Mark R Litzow
Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in >80% of patients if associated with multiorgan failure...
November 27, 2018: Blood Advances
Cecilie Utke Rank, Wendy Stock
Survival rates in adult patients with acute lymphoblastic leukemia (ALL) have markedly improved during the past decade. The one-size-fits-all-ages approach has been replaced with adaptation of pediatric-inspired treatment protocols for younger adults. Yet different treatment strategies for older patients are needed due to chemotherapy-related toxicities. A new era of immunotherapy has arrived, offering opportunities for targeted treatments for ALL subtypes. While CD20 targeting with rituximab has been demonstrated to improve survival when combined with chemotherapy, it has little activity as a single agent in ALL...
December 2018: Best Practice & Research. Clinical Haematology
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