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Adrian Wiestner
No abstract text is available yet for this article.
2024: Clinical Advances in Hematology & Oncology: H&O
#2
JOURNAL ARTICLE
Firas M Safa, Terri Rasmussen, Lorena Fontan, Min Xia, Ari Melnick, Adrian Wiestner, Patricia Lobelle-Rich, Jan A Burger, Yara Mouawad, Hana Safah, Erik K Flemington, Nakhle S Saba
B cell acute lymphoblastic leukemia (B-ALL) remains a hard-to-treat disease with a poor prognosis in adults. Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a para-caspase required for B-cell receptor (BCR)-mediated NF-κB activation. Inhibition of MALT1 in preclinical models has proven efficacious in many B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma and diffuse large B-cell lymphoma. We sought to examine the role of MALT1 in B-ALL and determine the biological consequences of its inhibition...
September 28, 2023: Haematologica
#3
JOURNAL ARTICLE
Emily Tomasulo, Shira Paul, Rui Mu, Xin Tian, Jonathan Chen, Christopher Pleyer, Adrian Wiestner, Clare Sun
B-cell targeted therapies, including anti-CD20 monoclonal antibodies (mAb) and Bruton's tyrosine kinase inhibitors (BTKi), further suppress antibody (Ab) response to vaccines in patients with chronic lymphocytic leukemia (CLL). We conducted a prospective cohort study of SARS-CoV-2 vaccination in 81 CLL patients receiving BTKi ( n = 54), venetoclax (VEN, n = 9), or who were treatment naïve (TN, n = 18). Anti-spike Ab were detected in 53% of patients on BTKi post-primary series and 84% post-booster, 57% of patients on VEN post-primary series and 50% post-booster, and 67% of TN patients post-primary series and 87% post-booster...
September 21, 2023: Leukemia & Lymphoma
#4
JOURNAL ARTICLE
Jennifer A Woyach, Paolo Ghia, John C Byrd, Inhye E Ahn, Carol Moreno, Susan M O'Brien, Daniel Jones, Leo W K Cheung, Elizabeth Chong, Kevin Kwei, James P Dean, Danelle F James, Adrian Wiestner
PURPOSE: Acquired mutations in Bruton's tyrosine kinase (BTK) or phospholipase C-γ2 (PLCG2) genes are associated with clinical progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) treated with BTK inhibitors. Data on mutation rates in patients without PD on ibrutinib treatment are limited. EXPERIMENTAL DESIGN: We evaluated frequency and time to detection of BTK and PLCG2 mutations in peripheral blood samples from 388 patients (n=238) or relapsed/refractory (n=150) CLL across 5 clinical trials...
June 14, 2023: Clinical Cancer Research
#5
JOURNAL ARTICLE
Anfal Alsadhan, Jonathan Chen, Erika M Gaglione, Chingiz Underbayev, Pamela L Tuma, Xin Tian, Lita A Freeman, Sivasubramanian Baskar, Pia Nierman, Susan Soto, Andy Itsara, Inhye E Ahn, Clare Sun, Elena Bibikova, Tanja Nicole Hartmann, Maissa Mhibik, Adrian Wiestner
PURPOSE: To determine the role of CD49d for response to Bruton's tyrosine kinase inhibitors (BTKi) in patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: In patients treated with acalabrutinib (n = 48), CD49d expression, VLA-4 integrin activation, and tumor transcriptomes of CLL cells were assessed. Clinical responses to BTKis were investigated in acalabrutinib- (n = 48; NCT02337829) and ibrutinib-treated (n = 73; NCT01500733) patients. RESULTS: In patients treated with acalabrutinib, treatment-induced lymphocytosis was comparable for both subgroups but resolved more rapidly for CD49d+ cases...
May 25, 2023: Clinical Cancer Research
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JOURNAL ARTICLE
Maissa Mhibik, Erika M Gaglione, David Eik, John Herrick, Janet Le, Inhye E Ahn, Christopher Chiu, Monica Wielgos-Bonvallet, Ida H Hiemstra, Esther C W Breij, Jenny Chen, Edward B Reilly, Pearlie K Epling-Burnette, Edith Szafer-Glusman, Clare Sun, Adrian Wiestner
Chronic lymphocytic leukemia (CLL) is an immunosuppressive disease characterized by increased infectious morbidity and inferior antitumor activity of immunotherapies. Targeted therapy with Bruton's tyrosine kinase inhibitors (BTKis) or the Bcl-2 inhibitor venetoclax has profoundly improved treatment outcomes in CLL. To overcome or prevent drug resistance and extend the duration of response after a time-limited therapy, combination regimens are tested. Anti-CD20 antibodies that recruit cell- and complement-mediated effector functions are commonly used...
August 8, 2023: Blood Advances
#7
JOURNAL ARTICLE
Anfal Alsadhan, Jonathan Chen, Erika M Gaglione, Chingiz Underbayev, Pamela L Tuma, Xin Tian, Lita A Freeman, Sivasubramanian Baskar, Pia Nierman, Susan Soto, Andy Itsara, Inhye E Ahn, Clare Sun, Elena Bibikova, Tanja Nicole Hartmann, Maissa Mhibik, Adrian Wiestner
PURPOSE: To determine the role of CD49d for response to Bruton's tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL). METHODS: In patients treated with acalabrutinib (n=48), CD49d expression, VLA-4 integrin activation, and tumor transcriptomes of CLL cells were assessed. Clinical responses to BTKis were investigated in acalabrutinib (n=48; NCT02337829), and ibrutinib (n=73; NCT01500733) treated patients. RESULTS: In patients treated with acalabrutinib, treatment induced lymphocytosis was comparable for both subgroups but resolved more rapidly for CD49d+ cases...
May 9, 2023: Clinical Cancer Research
#8
JOURNAL ARTICLE
McKensie A Collins, In-Young Jung, Ziran Zhao, Kimberly Apodaca, Weimin Kong, Stefan Lundh, Joseph A Fraietta, Arnon P Kater, Clare Sun, Adrian Wiestner, J Joseph Melenhorst
UNLABELLED: CD19-redirected chimeric antigen receptor (CAR) T cells have shown remarkable activity against B-cell cancers. While second-generation CARs induce complete remission in >80% of patients with acute lymphoblastic leukemia, similar monotherapy induces long-term remissions in only 26% of patients with chronic lymphocytic leukemia (CLL). This disparity is attributed to cell-intrinsic effector defects in autologous CLL-derived T cells. However, the mechanisms by which leukemic cells impact CAR T-cell potency are poorly understood...
September 2022: Cancer Res Commun
#9
EDITORIAL
Adrian Wiestner
No abstract text is available yet for this article.
October 2022: Seminars in Hematology
#10
JOURNAL ARTICLE
Matthew G Cyr, Maissa Mhibik, Junpeng Qi, Haiyong Peng, Jing Chang, Erika M Gaglione, David Eik, John Herrick, Thomas Venables, Scott J Novick, Valentine V Courouble, Patrick R Griffin, Adrian Wiestner, Christoph Rader
BACKGROUND: Despite numerous therapeutic options, safe and curative therapy is unavailable for most patients with chronic lymphocytic leukemia (CLL). A drawback of current therapies such as the anti-CD20 monoclonal antibody (mAb) rituximab is the elimination of all healthy B cells, resulting in impaired humoral immunity. We previously reported the identification of a patient-derived, CLL-binding mAb, JML-1, and identified sialic acid-binding immunoglobulin-like lectin-6 (Siglec-6) as the target of JML-1...
November 2022: Journal for Immunotherapy of Cancer
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JOURNAL ARTICLE
Deyi Zhang, Hailey M Harris, Jonathan Chen, Jennifer Toolan Judy, Gabriella James, Aileen Kelly, Joel McIntosh, Austin Tenn-McClellan, Eileen Rio Ambing, Ying Siow Tan, Hao Lu, Stefan Gajewski, Matthew C Clifton, Stephanie Yung, Daniel W Robbins, Mehdi Piroozia, Sigrid S Skånland, Erika M Gaglione, Maissa Mhibik, Chingiz Underbayev, Inhye Ahn, Clare Sun, Sarah E M Herman, Mark A Noviski, Adrian Wiestner
Bruton tyrosine kinase (BTK) is essential for B-cell receptor (BCR) signaling, a driver of chronic lymphocytic leukemia (CLL). Covalent inhibitors bind C481 in the active site of BTK and have become a preferred CLL therapy. Disease progression on covalent BTK inhibitors is commonly associated with C481 mutations. Here, we investigated a targeted protein degrader, NRX-0492, that links a non-covalent BTK binding domain to cereblon, an adaptor protein of the E3 ubiquitin ligase complex. NRX-0492 selectively catalyzes ubiquitylation and proteasomal degradation of BTK...
November 14, 2022: Blood
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JOURNAL ARTICLE
Emily Bryer, Shira Paul, Jonathan Chen, Christopher Pleyer, Adrian Wiestner, Clare Sun
INTRODUCTION: Patients with chronic lymphocytic leukemia (CLL) have inadequate responses to vaccination, including SARS-CoV-2 mRNA vaccines. Treatment with anti-B-cell therapies, such as anti-CD20 monoclonal antibodies (mAb) and Bruton's tyrosine kinase inhibitors (BTKi), further suppress the antibody response to vaccines. Here, we aimed to evaluate clinical and laboratory parameters associated with vaccine response and the effect of BTKi interruption around the time of booster. METHODS: A single-institution cohort study of patients with CLL was conducted at the National Institutes of Health...
October 2022: Clinical Lymphoma, Myeloma & Leukemia
#13
JOURNAL ARTICLE
Binyamin A Knisbacher, Ziao Lin, Cynthia K Hahn, Ferran Nadeu, Martí Duran-Ferrer, Kristen E Stevenson, Eugen Tausch, Julio Delgado, Alex Barbera-Mourelle, Amaro Taylor-Weiner, Pablo Bousquets-Muñoz, Ander Diaz-Navarro, Andrew Dunford, Shankara Anand, Helene Kretzmer, Jesus Gutierrez-Abril, Sara López-Tamargo, Stacey M Fernandes, Clare Sun, Mariela Sivina, Laura Z Rassenti, Christof Schneider, Shuqiang Li, Laxmi Parida, Alexander Meissner, François Aguet, Jan A Burger, Adrian Wiestner, Thomas J Kipps, Jennifer R Brown, Michael Hallek, Chip Stewart, Donna S Neuberg, José I Martín-Subero, Xose S Puente, Stephan Stilgenbauer, Catherine J Wu, Elias Campo, Gad Getz
Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the 'CLL map,' we integrated genomic, transcriptomic and epigenomic data from 1,148 patients...
November 2022: Nature Genetics
#14
JOURNAL ARTICLE
Olanrewaju A Ogunleye, Li-Yueh Hsu, Clare C Sun, Pia Nierman, Adrian Wiestner, Elizabeth C Jones, Hadi Bagheri
RATIONALE AND OBJECTIVES: To determine which methods of assessment of splenic size most accurately represent the actual spleen volume in patients with Chronic Lymphocytic Leukemia (CLL). MATERIALS AND METHODS: The Abdominal Computed Tomography images of 48 patients with CLL enrolled on a phase 2 clinical trial at two time-points before and after 2-months of continuous acalabrutinib treatment were analyzed. Linear one-dimensional measurements of the spleen were taken in different planes...
July 19, 2022: Academic Radiology
#15
JOURNAL ARTICLE
Adrian Wiestner, Surapol Issaragrisil, David W Kaufman, Keiya Ozawa, Shinji Nakao, Sachiko Kajigaya, Jianxiang Wang, Zhijie Wu, Vo Thi Thanh Binh, Rishi Dhawan, Velu Nair
No abstract text is available yet for this article.
January 2022: Seminars in Hematology
#16
EDITORIAL
Adrian Wiestner
No abstract text is available yet for this article.
January 2022: Seminars in Hematology
#17
JOURNAL ARTICLE
Clare Sun, Yun-Ching Chen, Aina Z Martinez, Maria Joao Baptista, Stefania Pittaluga, Delong Liu, Daniel Rosebrock, Satyen H Gohil, Nakhle S Saba, Theresa Davies-Hill, Sarah E M Herman, Gad Getz, Mehdi Pirooznia, Catherine J Wu, Adrian Wiestner
In chronic lymphocytic leukemia (CLL), B-cell receptor signaling, tumor-microenvironment interactions and somatic mutations drive disease progression. To better understand the intersection between the microenvironment and molecular events in CLL pathogenesis, we integrated bulk transcriptome profiling of paired peripheral blood (PB) and lymph node (LN) samples from 34 patients. Oncogenic processes were upregulated in LN compared to PB, and in IGHV unmutated compared to mutated cases. Single-cell RNA sequencing distinguished 3 major cell states: quiescent, activated, and proliferating...
March 31, 2022: Blood Advances
#18
RANDOMIZED CONTROLLED TRIAL
Rahul Lakhotia, Christopher Melani, Kieron Dunleavy, Stefania Pittaluga, Nakhle Saba, Liza Lindenberg, Esther Mena, Ethan Bergvall, Andrea Nicole Lucas, Allison Jacob, Erik Yusko, Seth M Steinberg, Elaine S Jaffe, Adrian Wiestner, Wyndham H Wilson, Mark Roschewski
Mantle cell lymphoma (MCL) is biologically and clinically heterogeneous and would benefit from prognostic biomarkers to guide management. Circulating tumor DNA (ctDNA) is a novel prognostic biomarker in diffuse large B-cell lymphoma that may have applicability in MCL. We analyzed ctDNA dynamics in previously untreated patients with MCL who received induction therapy with bortezomib and DA-EPOCH-R for 6 cycles followed by random assignment to observation or bortezomib maintenance in responding patients in a prospective phase 2 study...
April 26, 2022: Blood Advances
#19
JOURNAL ARTICLE
John N Allan, Tait Shanafelt, Adrian Wiestner, Carol Moreno, Susan M O'Brien, Jianling Li, Gabriel Krigsfeld, James P Dean, Inhye E Ahn
TP53 aberrations [del(17p) or TP53 mutation] predict poor survival with chemoimmunotherapy in patients with chronic lymphocytic leukaemia (CLL). We evaluated long-term efficacy and safety of first-line ibrutinib-based therapy in patients with CLL bearing TP53 aberrations in a pooled analysis across four studies: PCYC-1122e, RESONATE-2 (PCYC-1115/16), iLLUMINATE (PCYC-1130) and ECOG-ACRIN E1912. The pooled analysis included 89 patients with TP53 aberrations receiving first-line treatment with single-agent ibrutinib (n = 45) or ibrutinib in combination with an anti-CD20 antibody (n = 44)...
December 5, 2021: British Journal of Haematology
#20
JOURNAL ARTICLE
Arshia Soleimani, Alba Navarro, Delong Liu, Sarah E M Herman, Shih-Sung Chuang, Irma Slavutsky, Marina Narbaitz, Hana Safah, John Schmieg, John Lefante, Mark Roschewski, Wyndham H Wilson, Adrian Wiestner, Nakhle S Saba
Conventionally, mantle cell lymphoma (MCL) is an aggressive CD5-positive B-cell malignancy with poor prognosis and limited survival. However, a small subset of patients presents with indolent disease and can be managed on a 'watch and wait' approach. CD5-negative MCL has recently been recognized as a more favorable variant of MCL, but its clinical and biological implications remain ill-defined. We performed the most extensive review to-date of all reported cases of CD5-negative MCL and included unpublished cases diagnosed at our institutions to further characterize this disease subset...
April 2022: Leukemia & Lymphoma
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