Search

Your search keyword '"Leukam, Michael"' showing total 19 results
Start Over Author "Leukam, Michael"
19 results on '"Leukam, Michael"'

2. CREBBP histone acetyltransferase domain mutations predict response to mTOR inhibition in relapsed/refractory follicular lymphoma.

Author

Kumar, Emil Arjun, Korfi, Koorosh, Bewicke‐Copley, Findlay, Close, Karina, Heward, James, Witzig, Thomas, Leukam, Michael, Ansell, Stephen, Scott, Jessica, Clear, Andrew, Efeyan, Alejo, Green, Michael, Siebert, Reiner, Peck, Barrie, Calaminici, Maria, Wang, Jun, Smith, Sonali, Novak, Anne, Fitzgibbon, Jude, and Okosun, Jessica

Subjects
HISTONE acetyltransferase, FOLLICULAR lymphoma, GENETIC mutation, GENETICS, CLINICAL trials
Abstract

Summary: Despite the clinical and molecular heterogeneity of follicular lymphoma (FL), there remains a lack of biomarker‐directed therapeutic approaches in routine clinical practice, with the notable exception of the EZH2 inhibitor tazemetostat in EZH2‐mutant FL. Here we examined whether gene mutation status predicts response to clinical mTOR inhibitors (mTORi) in FL, by performing targeted mutational profiling of biopsies from 21 relapsed/refractory FL patients treated with mTORi everolimus or temsirolimus within clinical trials. We observed an enrichment of mutations within the catalytic histone acetyltransferase (HAT) domain of CREBBP in mTORi‐responders, and describe distinct transcriptional characteristics and co‐occurring mutations of FL harbouring these mutations; reinforcing the growing appreciation of CREBBPHAT mutation as a key biological determinant and its promise as a therapeutic biomarker in FL. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

6. G-CSF Administration Is Associated with Worse Treatment Response and Survival after CAR T-Cell Therapy

Author

Bindal, Poorva, primary, Elavalakanar, Pavania, additional, Trottier, Caitlin A., additional, Dodge, Laura E., additional, Logan, Emma K., additional, Sermer, David J., additional, Leukam, Michael, additional, Weinstock, Matthew J, additional, Joyce, Robin M., additional, Liegel, Jessica, additional, Rosenblatt, Jacalyn, additional, Avigan, David, additional, Alonso, Carolyn D., additional, and Arnason, Jon E., additional

Published
2022
Full Text
View/download PDF

7. A Novel Combination of TGF-β Inhibitor and DC/AML Fusion Vaccine for Management of AML in an Immunocompetent Murine Model

Author

Bindal, Poorva, primary, Liegel, Jessica, additional, Stroopinsky, Dina, additional, Koshy, Anita G., additional, Cheloni, Giulia, additional, Leukam, Michael, additional, Torres, Daniela, additional, Hauser, Joshua, additional, Dufort, Kenel, additional, Yoo, Seo Yeon, additional, Kufe, Donald, additional, Wucherpfennig, Kai, additional, Rosenblatt, Jacalyn, additional, and Avigan, David, additional

Published
2022
Full Text
View/download PDF

8. Corticosteroids, Tocilizumab or Filgrastim Do Not Impact the Efficacy of CAR T-Cell Therapy with 4- 1BB Costimulatory Domain

Author

Bindal, Poorva, primary, Trottier, Caitlin, additional, Dodge, Laura E., additional, Elavalakanar, Pavania, additional, Knudsen, Elisabeth, additional, Logan, Emma, additional, Kim, Sirwoo, additional, Urman, Arielle, additional, Sermer, David J., additional, Leukam, Michael, additional, Jain, Salvia, additional, Weinstock, Matthew, additional, Joyce, Robin M., additional, Alonso, Carolyn D., additional, and Arnason, Jon E., additional

Published
2022
Full Text
View/download PDF

15. Refining patient selection for CAR T-cell therapy in aggressive large B-cell lymphoma.

Author

Cahill, Kirk E., Leukam, Michael J., and Riedell, Peter A.

Subjects
*PATIENT selection, *CHIMERIC antigen receptors, *DIFFUSE large B-cell lymphomas, *CELLULAR therapy, *DISEASE remission
Abstract

Relapsed or refractory non-Hodgkin B-cell lymphoma is an aggressive disease with a dismal prognosis. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a viable treatment option with durable remissions observed in clinical trials. Due to the risk of toxicities such as cytokine release syndrome and neurotoxicity, careful patient selection is critical to optimize outcomes. Narrow selection criteria were used in clinical trials that led to approval, but a wider range of patients has been successfully treated in the commercial setting. Due to lack of validated pretreatment clinical factors, including risk scores or biomarkers to predict efficacy and toxicity, choosing candidates for CAR T-cell therapy currently relies on expert opinion. Because of logistical constraints and often aggressive disease, we favor referring patients early for cellular therapy at the time of first treatment failure. Herein, we discuss criteria for patient selection using a case-based approach informed by reports of real-world outcomes. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

16. Evaluation of a pre-transplant serum biomarker score for allogeneic hematopoietic stem cell transplant (HCT) and association with clinical factors.

Author

Leukam, Michael, primary, Kocherginsky, Masha, additional, Godley, Lucy A., additional, Kline, Justin Paul, additional, Larson, Richard A., additional, Liu, Hongtao, additional, Odenike, Olatoyosi, additional, Stock, Wendy, additional, Bishop, Michael Russell, additional, and Artz, Andrew S., additional

Published
2016
Full Text
View/download PDF

17. PD-L1gene alterations identify a subset of diffuse large B-cell lymphoma harboring a T-cell–inflamed phenotype

Author

Godfrey, James, Tumuluru, Sravya, Bao, Riyue, Leukam, Michael, Venkataraman, Girish, Phillip, John, Fitzpatrick, Carrie, McElherne, James, MacNabb, Brendan W., Orlowski, Robert, Smith, Sonali M., and Kline, Justin

Abstract

Programmed death-ligand 1 (PD-L1) expression on malignant cells is a dominant immune escape mechanism across a variety of human cancers. A unique genetic mechanism underlying PD-L1 upregulation has been uncovered in classical Hodgkin lymphoma (cHL), in which copy gains of the chromosomal region (9p24.1) containing the programmed death-1 (PD-1) ligands PD-L1and PD-L2are recurrently observed. While chromosome 9p24.1 copy-number alterations are ubiquitous in cHL, they also occur in diffuse large B-cell lymphoma (DLBCL), albeit with a lower incidence. Here, fluorescence in situ hybridization was used to identify DLBCLs harboring PD-L1gene alterations, thereby enabling a characterization of the immunogenomic landscape of these lymphomas. Among 105 DLBCL cases analyzed, PD-L1alterations were identified in 27%. PD-L1alterations were highly enriched among non–germinal center DLBCLs and exhibited robust PD-L1 protein expression. These lymphomas were heavily infiltrated by clonally restricted T cells and frequently downregulated human leukocyte antigen expression. RNA sequencing of PD-L1–altered DLBCLs revealed upregulation of genes involved in negative T-cell regulation and NF-κB pathway activation, while whole-exome sequencing identified frequent mutations in genes involved in antigen presentation and T-cell costimulation. Many of these findings were validated in a large external data set. Interestingly, DLBCL patients with PD-L1alterations had inferior progression-free survival following front-line chemoimmunotherapy; however, in the relapsed/refractory setting, PD-L1alterations were associated with response to anti-PD-1 therapy. Collectively, our results indicate that PD-L1alterations identify a unique biological subset of DLBCL in which an endogenous antilymphoma immune response has been activated, and that is associated with responsiveness to PD-1 blockade therapy.

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results