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Article: Editorial: Novel mechanisms for the treatment of AML before and after transplant.

Kasner, Margaret T

2022 Volume 12, Page(s) 1063307

Language	English
Publishing date	2022-10-31
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.1063307
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Outpatient administration of liposomal daunorubicin and cytarabine (Vyxeos) in patients with secondary acute myeloid leukemia.

Kasner, Margaret T

Clinical advances in hematology & oncology : H&O

2020 Volume 17, Issue 11, Page(s) 604–606

MeSH term(s)	Ambulatory Care/methods ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Clinical Trials as Topic ; Cytarabine/administration & dosage ; Daunorubicin/administration & dosage ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/pathology ; Liposomes/chemistry ; Neoplasms, Second Primary/drug therapy ; Neoplasms, Second Primary/pathology ; Treatment Outcome
Chemical Substances	Liposomes ; Cytarabine (04079A1RDZ) ; Daunorubicin (ZS7284E0ZP)
Language	English
Publishing date	2020-01-08
Publishing country	United States
Document type	Interview
ZDB-ID	2271951-9
ISSN	1543-0790
ISSN	1543-0790
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Zs.A 6505: Show issues

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Article ; Online: A phase Ib dose escalation study of oral monotherapy with KX2-391 in elderly patients with acute myeloid leukemia.

Kasner, Margaret T / Halloran, Molly B / Pan, Jonathan / Ritchie, Ellen K / Fetterly, Gerald J / Kramer, Douglas / Hangauer, David G / Thompson, James E

Investigational new drugs

2022 Volume 40, Issue 4, Page(s) 773–781

Abstract: Poor tolerance to standard therapies and multi-drug resistance complicate treatment of elderly patients with acute myeloid leukemia (AML). It is therefore imperative to explore novel tolerable agents and target alternative pathways. KX2-391 is an oral ... ...

Abstract	Poor tolerance to standard therapies and multi-drug resistance complicate treatment of elderly patients with acute myeloid leukemia (AML). It is therefore imperative to explore novel tolerable agents and target alternative pathways. KX2-391 is an oral non-ATP-competitive inhibitor of Src kinase and tubulin polymerization. This multi-center phase Ib open-label safety and activity study involved elderly patients with relapsed or refractory AML, or who declined standard chemotherapy. Twenty-four patients averaging 74 years of age were enrolled. The majority previously received hypomethylating agents. Five doses were tested: 40 mg (n = 1), 80 mg (n = 2), 120 mg (n = 8), 140 mg (n = 12), and 160 mg (n = 1). Seven patients were treated for 12 days or less, nine for 15-29 days, five for 33-58 days, and three for 77-165 days. One patient receiving 120 mg for 165 days had reduced splenomegaly and survived 373 days. Another had no evidence of disease progression for 154 days. One patient receiving 160 mg for 12 days remained treatment-free for about 18 months. Dose-limiting toxicities occurred in eight patients at: 120 mg (transaminitis, hyperbilirubinemia), 140 mg (mucositis, allergic reaction, transaminitis, acute kidney injury), and 160 mg (mucositis). The maximum tolerated dose for KX2-391 was 120 mg once daily. KX2-391 bone marrow concentrations were approximately similar to plasma concentrations. This is the first study to evaluate the safety of KX2-391 in elderly patients with AML. Further studies are warranted, including alternative dosing phase I trials evaluating shorter courses at higher doses and phase II trials. (Clinical Trial Registration:The study was registered at ClinicalTrials.gov: NCT01397799 (July 20, 2011)).
MeSH term(s)	Acetamides ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Maximum Tolerated Dose ; Morpholines/therapeutic use ; Mucositis/drug therapy ; Pyridines
Chemical Substances	Acetamides ; Morpholines ; Pyridines ; tirbanibulin
Language	English
Publishing date	2022-05-17
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	604895-x
ISSN	1573-0646 ; 0167-6997
ISSN (online)	1573-0646
ISSN	0167-6997
DOI	10.1007/s10637-022-01255-1
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Zs.A 1823: Show issues

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Article ; Online: Novel targets for treatment of adult acute lymphocytic leukemia.

Kasner, Margaret T

Current hematologic malignancy reports

2010 Volume 5, Issue 4, Page(s) 207–212

Abstract: The treatment of acute lymphocytic leukemia (ALL) results in long-term disease-free survival in only 30-40% of adults. Conventional chemotherapy is toxic and woefully ineffective. Therefore, novel agents are being investigated. Among these agents are ... ...

Abstract	The treatment of acute lymphocytic leukemia (ALL) results in long-term disease-free survival in only 30-40% of adults. Conventional chemotherapy is toxic and woefully ineffective. Therefore, novel agents are being investigated. Among these agents are monoclonal antibodies such as rituximab, epratuzumab, and alemtuzumab and targeted therapies such as tyrosine kinase inhibitors, mTOR inhibitors, and mitogen-activated protein kinase (MEK) inhibitors. This article discusses such novel targets for the treatment of ALL.
MeSH term(s)	Alemtuzumab ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antibodies, Neoplasm/therapeutic use ; Antineoplastic Agents/therapeutic use ; Humans ; Mitogen-Activated Protein Kinases/antagonists & inhibitors ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Protein Kinase Inhibitors/therapeutic use ; Rituximab ; TOR Serine-Threonine Kinases/antagonists & inhibitors
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal, Murine-Derived ; Antibodies, Neoplasm ; Antineoplastic Agents ; Protein Kinase Inhibitors ; epratuzumab (3062P60MH9) ; Alemtuzumab (3A189DH42V) ; Rituximab (4F4X42SYQ6) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2010-07-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2229765-0
ISSN	1558-822X ; 1558-8211
ISSN (online)	1558-822X
ISSN	1558-8211
DOI	10.1007/s11899-010-0064-8
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Zs.A 6332: Show issues

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Article: Accrual-Monitoring Practices for Various Disease Trials among AACI Member Cancer Centers.

Elliott, Zachary T / Goldberg, Zachary / Philips, Ramez / Johnson, Jennifer M / Kasner, Margaret T / Kelly, William K / Osipowicz, Sarah / Dampman, Rachael / Curry, Joseph M

Clinics and practice

2022 Volume 12, Issue 5, Page(s) 692–700

Abstract: Progress in the management of rare diseases, including rare cancers, is dependent upon clinical trials; however, as many as 32% of rare-disease trials go uncompleted or unpublished due to insufficient accrual. Monitoring practices may differ between ... ...

Abstract	Progress in the management of rare diseases, including rare cancers, is dependent upon clinical trials; however, as many as 32% of rare-disease trials go uncompleted or unpublished due to insufficient accrual. Monitoring practices may differ between institutions. We sought to survey the regulatory standards for various trial types among major U.S. cancer centers. A 10-question survey was designed using Qualtrics assessment software. The survey was sent via email to an internal server of member institutions of the Association of American Cancer Institutes (AACI). Of 103 AACI centers, 31% completed the survey (
Language	English
Publishing date	2022-08-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2605724-4
ISSN	2039-7283 ; 2039-7275
ISSN (online)	2039-7283
ISSN	2039-7275
DOI	10.3390/clinpract12050072
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Article ; Online: Polo-like kinase and its inhibitors: Ready for the match to start?

Palmisiano, Neil D / Kasner, Margaret T

American journal of hematology

2015 Volume 90, Issue 11, Page(s) 1071–1076

Abstract: Polo-like kinases (Plks) plays a central role in the normal cell cycle and their upregulation has been shown to play a role in the pathogenesis of multiple human cancers. Preclinical work demonstrates that targeting Plk has a significant impact on the ... ...

Abstract	Polo-like kinases (Plks) plays a central role in the normal cell cycle and their upregulation has been shown to play a role in the pathogenesis of multiple human cancers. Preclinical work demonstrates that targeting Plk has a significant impact on the treatment of both solid and hematologic malignancies in vitro and in vivo. We review here the basic science and clinical work to date with the Plks as well as future directions with this novel class of mitotic inhibitors.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Cell Cycle/drug effects ; Cell Cycle/genetics ; Cell Cycle Proteins/antagonists & inhibitors ; Cell Cycle Proteins/genetics ; Clinical Trials as Topic ; Gene Expression ; Hematologic Neoplasms/diagnosis ; Hematologic Neoplasms/drug therapy ; Hematologic Neoplasms/genetics ; Hematologic Neoplasms/mortality ; Humans ; Isoenzymes/antagonists & inhibitors ; Isoenzymes/genetics ; Mice ; Protein Kinase Inhibitors/therapeutic use ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Protein Serine-Threonine Kinases/genetics ; Proto-Oncogene Proteins/antagonists & inhibitors ; Proto-Oncogene Proteins/genetics ; Survival Analysis ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Polo-Like Kinase 1
Chemical Substances	Antineoplastic Agents ; Cell Cycle Proteins ; Isoenzymes ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins ; Tumor Suppressor Protein p53 ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2015-10-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.24177
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Zs.A 1251: Show issues

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Article: Treatment of adult ALL: more questions than answers.

Kasner, Margaret T / Weiss, Mark

Oncology (Williston Park, N.Y.)

2012 Volume 26, Issue 9, Page(s) 865, 869–70

MeSH term(s)	Humans ; Molecular Targeted Therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Salvage Therapy ; Therapies, Investigational
Language	English
Publishing date	2012-09
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	1067950-9
ISSN	0890-9091
ISSN	0890-9091
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Zs.A 3168: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 372: Show issues

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Article ; Online: Update on the therapy for myelodysplastic syndrome.

Kasner, Margaret T / Luger, Selina M

American journal of hematology

2009 Volume 84, Issue 3, Page(s) 177–186

Abstract: The myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic stem cell disorders characterized by cytopenias. Patients have a risk of developing acute leukemia though most succumb to complications of low blood counts. Over the past ... ...

Abstract	The myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic stem cell disorders characterized by cytopenias. Patients have a risk of developing acute leukemia though most succumb to complications of low blood counts. Over the past decade many novel treatments have been developed and investigation of new agents is ongoing. In this article, we discuss the classification and prognostic systems that are used in MDS, the agents available for treatment of MDS as well as review supportive and palliative care options for patients who are not candidates for, or opt against, newer treatment strategies.
MeSH term(s)	Aged ; Antimetabolites, Antineoplastic/therapeutic use ; Clinical Trials as Topic ; Drug Design ; Hematopoietic Stem Cell Transplantation ; Humans ; Middle Aged ; Myelodysplastic Syndromes/classification ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/therapy ; Risk Factors
Chemical Substances	Antimetabolites, Antineoplastic
Language	English
Publishing date	2009-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.21352
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1251: Show issues

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Article: A Phase I Trial of Sirolimus with "7&3" Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukemia.

Palmisiano, Neil / Jeschke, Grace / Wilde, Lindsay / Alpdogan, Onder / Carabasi, Matthew / Filicko-O'Hara, Joanne / Grosso, Dolores / Klumpp, Thomas / Martinez, Ubaldo / Wagner, John / Carroll, Martin P / Perl, Alexander / Kasner, Margaret

Cancers

2023 Volume 15, Issue 21

Abstract: Chemotherapy remains a primary treatment for younger AML patients, though many relapse. Data from our group have shown that highly phosphorylated S6 in blasts may predict response to sirolimus given with chemotherapy. We report the results of a phase I ... ...

Abstract	Chemotherapy remains a primary treatment for younger AML patients, though many relapse. Data from our group have shown that highly phosphorylated S6 in blasts may predict response to sirolimus given with chemotherapy. We report the results of a phase I study of this combination in newly diagnosed AML and the pharmacodynamic analysis of pS6 before and after treatment. Subjects received sirolimus (12 mg on day 1, 4 mg daily, days 2-10), then idarubicin and cytarabine (days 4-10). Response was assessed at hematologic recovery or by day 42 using a modified IWG criteria. Fifty-five patients received sirolimus. Toxicity was similar to published 7 + 3 data, and 53% had high-, 27% intermediate-, and 20% favorable-risk disease. Forty-four percent of the high-risk patients entered into CR/CRp. Seventy-nine percent of the intermediate-risk subjects had a CR/CRp. All favorable-risk patients had a CR by day 42; 9/11 remained alive and in remission with a median follow-up of 660 days. Additionally, 41/55 patients had adequate samples for pharmacodynamic analysis. All patients demonstrated activation of S6 prior to therapy, in contrast to 67% seen in previous studies of relapsed AML. mTORC1 inhibition was observed in 66% of patients without enrichment among patients who achieved remission. We conclude that sirolimus and 7 + 3 is a well-tolerated and safe regimen. mTORC1 appears to be activated in almost all patients at diagnosis of AML. Inhibition of mTORC1 did not differ based on response, suggesting that AML cells may have redundant signaling pathways that regulate chemosensitivity in the presence of mTORC1 inhibition.
Language	English
Publishing date	2023-10-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15215129
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Article: CCL2 and CXCL10 are associated with poor outcome after intracerebral hemorrhage.

Landreneau, Margaret J / Mullen, Michael T / Messé, Steven R / Cucchiara, Brett / Sheth, Kevin N / McCullough, Louise D / Kasner, Scott E / Sansing, Lauren H

Annals of clinical and translational neurology

2018 Volume 5, Issue 8, Page(s) 962–970

Abstract: Objective: Intracerebral hemorrhage carries a high mortality and survivors are frequently left with significant disability. Immunological mechanisms may play an important role in hemorrhage-induced brain injury, however, research linking these ... ...

Abstract	Objective: Intracerebral hemorrhage carries a high mortality and survivors are frequently left with significant disability. Immunological mechanisms may play an important role in hemorrhage-induced brain injury, however, research linking these mechanisms with clinical outcome remains limited. We aim to identify serum inflammatory mediators that are associated with outcome after intracerebral hemorrhage in order to translate data from experimental models to a patient cohort and identify potential targets worthy of reverse translation. Methods: A prospective cohort study at two comprehensive stroke centers enrolled patients with spontaneous intracerebral hemorrhage. Peripheral blood was collected at 6, 24, and 72 h from onset. Functional outcome was assessed at 90 days using the modified Rankin Scale (mRS). Serum inflammatory mediators were measured using multiplex ELISA. Multivariable modeling identified serum biomarkers independently associated with functional outcome at 90 days. Results: 115 patients completed the study. At 6 h after onset, patients with elevated CCL2 had worse mRS score at day 90 (OR 4.07, 95% CI 1.27-13.10, Interpretation: Acute and subacute elevations in specific immune factors are associated with poor outcome, highlighting potential pathways that may contribute to ongoing brain injury in patients with intracerebral hemorrhage.
Language	English
Publishing date	2018-07-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2740696-9
ISSN	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.595
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