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The Australasian Journal of Dermatology Aug 2021We report the case of a 59-year-old woman with stage IV erythrodermic mycosis fungoides (MF) and large cell transformation who, despite failing multiple previous...
Complete remission of stage IV erythrodermic mycosis fungoides with large cell transformation through combination of pralatrexate and romidepsin followed by allogeneic hematopoietic stem cell transplantation.
We report the case of a 59-year-old woman with stage IV erythrodermic mycosis fungoides (MF) and large cell transformation who, despite failing multiple previous treatments, achieved complete remission through a combination of pralatrexate and romidepsin followed by allogeneic hematopoietic stem cell transplantation (alloSCT). Further studies are needed in focussing on this combined regimen in treating cutaneous T-cell lymphoma (CTCL) and its efficacy as a bridging regimen in facilitating successful alloSCT.
Topics: Aminopterin; Antibiotics, Antineoplastic; Depsipeptides; Female; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Mycosis Fungoides; Remission Induction; Skin Neoplasms; Treatment Outcome
PubMed: 34028795
DOI: 10.1111/ajd.13606 -
Seminars in Hematology Apr 2021Peripheral T-cell lymphomas (PTCL) are rare lymphoproliferative disorders with poor outcomes and high rates of relapse. Incidence varies although the most common...
Peripheral T-cell lymphomas (PTCL) are rare lymphoproliferative disorders with poor outcomes and high rates of relapse. Incidence varies although the most common subtypes include PTCL-not-otherwise specified, anaplastic large cell lymphoma, and angioimmunoblastic T-cell lymphoma. Anaplastic large cell lymphoma is characterized by near-universal CD30 expression and serves as a prototypic model for other CD30-expressing lymphomas. Historically, these neoplasms have been treated with regimens used in the treatment of aggressive B-cell lymphomas. Over the last decade, brentuximab vedotin, an antibody-drug conjugate, has been investigated to treat peripheral T-cell lymphomas expressing CD30. While first studied in the relapsed and refractory setting, it was later studied in the frontline setting in the ECHELON-2 trial with positive results and is now an approved treatment for CD30-expressing peripheral T-cell lymphomas. Other treatment options in the relapsed and refractory setting include histone deacetylase inhibitors, pralatrexate, and salvage multiagent chemotherapy regimens. Current research is underway regarding combination therapies and the use of other novel agents.
Topics: Brentuximab Vedotin; Humans; Immunoconjugates; Ki-1 Antigen; Lymphoma, Large-Cell, Anaplastic; Lymphoma, T-Cell, Peripheral; Neoplasm Recurrence, Local
PubMed: 33906726
DOI: 10.1053/j.seminhematol.2021.02.006 -
Biomolecules & Therapeutics May 2021Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global...
Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.
PubMed: 33731494
DOI: 10.4062/biomolther.2021.032 -
Leukemia Jun 2021Folate-mediated one carbon (1C) metabolism supports a series of processes that are essential for the cell. Through a number of interlinked reactions happening in the... (Review)
Review
Folate-mediated one carbon (1C) metabolism supports a series of processes that are essential for the cell. Through a number of interlinked reactions happening in the cytosol and mitochondria of the cell, folate metabolism contributes to de novo purine and thymidylate synthesis, to the methionine cycle and redox defence. Targeting the folate metabolism gave rise to modern chemotherapy, through the introduction of antifolates to treat paediatric leukaemia. Since then, antifolates, such as methotrexate and pralatrexate have been used to treat a series of blood cancers in clinic. However, traditional antifolates have many deleterious side effects in normal proliferating tissue, highlighting the urgent need for novel strategies to more selectively target 1C metabolism. Notably, mitochondrial 1C enzymes have been shown to be significantly upregulated in various cancers, making them attractive targets for the development of new chemotherapeutic agents. In this article, we present a detailed overview of folate-mediated 1C metabolism, its importance on cellular level and discuss how targeting folate metabolism has been exploited in blood cancers. Additionally, we explore possible therapeutic strategies that could overcome the limitations of traditional antifolates.
Topics: Animals; Antineoplastic Agents; Carbon; Folic Acid; Folic Acid Antagonists; Hematologic Neoplasms; Humans
PubMed: 33707653
DOI: 10.1038/s41375-021-01189-2 -
Spectrochimica Acta. Part A, Molecular... May 2021In this study, a series of green, interference-free fluorimetric detection methods of the excitation-emission matrix coupled with the second-order calibration methods...
Three efficient chemometrics assisted fluorimetric detection methods for interference-free, rapid, and simultaneous determination of ibrutinib and pralatrexate in various complicated biological fluids.
In this study, a series of green, interference-free fluorimetric detection methods of the excitation-emission matrix coupled with the second-order calibration methods were proposed for the determination of ibrutinib and pralatrexate in various complicated biological fluids. The second-order advantage of the proposed method can overcome the problem of poor selectivity caused by the wide spectra of the fluorescence method. Even in the presence of uncalibrated interferences and severe peak overlap, the signal of pure substance and accurate quantitative results were still obtained. The average recoveries of the three methods were 94.5-104.9% for Alternating Trilinear Decomposition (ATLD) algorithm, 95.5-105.8% for Alternating Normalization Weighted Error (ANWE) algorithm and 94.4-105.7% for Parallel Factor Analysis (PARAFAC) algorithm, respectively. For ATLD, ANWE and PARAFAC, the relative standard deviations (RSD) were lower than 9.2%, 6.8% and 9.2%, and the RMSEPs were less than 8.1, 8.4 and 8.6 ng mL, respectively. In addition, the elliptic joint confidence region (EJCR) was adopted to further prove the accuracy of the three methods. The results showed that the three methods can accurately be quantified without significant difference. Good figures of merit parameters were also obtained. Among them, the limit of detection (LOD) and limit of quantification (LOQ) of ibrutinib and pralatrexate were in the range of 0.11-0.76 ng mL and 0.21-1.12 ng mL, respectively, which were lower than the corresponding blood concentrations. These results indicate that the proposed method provides a promising, alternative and universal analysis strategy for clinical drug monitoring.
Topics: Adenine; Algorithms; Aminopterin; Calibration; Fluorometry; Limit of Detection; Piperidines; Spectrometry, Fluorescence
PubMed: 33524816
DOI: 10.1016/j.saa.2020.119419 -
Expert Opinion on Pharmacotherapy Jun 2021Peripheral T cell lymphomas (PTCL) are a group of heterogenous hematologic malignancies derived from post-thymic T lymphocytes and mature NK cells. Conventional...
INTRODUCTION
Peripheral T cell lymphomas (PTCL) are a group of heterogenous hematologic malignancies derived from post-thymic T lymphocytes and mature NK cells. Conventional chemotherapy does not guarantee a good outcome.
AREAS COVERED
The article summarizes recent investigational therapies and their mechanism of action, as well as the pharmacological properties, clinical activity, and toxicity of new agents in the treatment of primary nodal PTCLs. The review scrutinized papers included in the MEDLINE (PubMed) database between 2010 and October 2020. These were supplemented with a manual search of conference proceedings from the previous five years of the American Society of Hematology, European Hematology Association, and American Society of Clinical Oncology. Further relevant publications were obtained by reviewing the references from the chosen articles.
EXPERT OPINION
PTCLs have proved difficult to treat and investigate because of their rarity. Studies of aggressive lymphoma, including a small proportion of T-cell lymphomas, found that any benefit from intensified traditional chemotherapy in patients with PTCL is accompanied by increased toxicity. However, the management of PTCL is beginning to change dramatically, thanks to the use of more sophisticated agents targeting the mechanisms of disease development.
Topics: Humans; Lymphoma, T-Cell, Peripheral
PubMed: 33524268
DOI: 10.1080/14656566.2021.1882997 -
Oncoscience Nov 2020
PubMed: 33457448
DOI: 10.18632/oncoscience.520 -
The Journal of Dermatology May 2021Pralatrexate has been approved for the treatment of relapsed/refractory peripheral T cell lymphomas. Studies in the U.S. also support the clinical efficacy of...
Pralatrexate has been approved for the treatment of relapsed/refractory peripheral T cell lymphomas. Studies in the U.S. also support the clinical efficacy of pralatrexate to treat advanced-stage cutaneous T-cell lymphomas, but outcomes in Japanese patients have not yet been reported. We herein describe two Japanese patients with heavily-pretreated relapsed/refractory mycosis fungoides that were successfully controlled by pralatrexate.
Topics: Aminopterin; Humans; Japan; Mycosis Fungoides; Neoplasm Recurrence, Local; Skin Neoplasms
PubMed: 33454985
DOI: 10.1111/1346-8138.15761 -
Current Treatment Options in Oncology Jan 2021While most patients with early-stage mycosis fungoides (MF) follow an indolent course, patients with advanced-stage MF/Sézary syndrome (SS) have a poor prognosis with a... (Review)
Review
While most patients with early-stage mycosis fungoides (MF) follow an indolent course, patients with advanced-stage MF/Sézary syndrome (SS) have a poor prognosis with a median survival of less than 5 years. Although there are a number of treatments currently available, achieving and maintaining a durable response remain challenging, especially in advanced-stage MF/SS. The choice of frontline therapy is dependent on the stage of disease. For early-stage MF, the treatment concept is to control skin lesions mainly by skin-directed therapies, such as topical therapies, phototherapies, and radiotherapies. For advanced-stage MF/SS, systemic treatments by biological or targeted therapies including bexarotene and interferon either alone or in combination are tried first, with more immunosuppressive chemotherapies being reserved for refractory or rapidly progressive disease. Recent improvements in biological or targeted therapies include brentuximab vedotin and mogamulizumab. When biopsy samples have 10% or more CD30-positive malignant cells, brentuximab vedotin, an anti-CD30 antibody conjugated to monomethyl auristin E, can be a desirable treatment option. For cases with blood involvement, mogamulizumab, an antibody binding to C-C chemokine receptor 4, is effective with high response rates. In the refractory setting, alemtuzumab, histone deacetylase inhibitors, pralatrexate, gemcitabine, and doxorubicin are considered as the treatment option. Because only allogeneic hematopoietic stem cell transplantation can offer a chance of cure with durable complete remission, advanced-stage patients with a markedly short life expectancy should be evaluated for eligibility. Given that there are few randomized controlled studies in the literature, it is necessary to investigate which therapy is preferable for each patient with MF/SS by comparative prospective trials.
Topics: Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Progression; Humans; Mycosis Fungoides; Neoplasm Grading; Neoplasm Staging; Prognosis; Sezary Syndrome; Skin Neoplasms; Treatment Outcome
PubMed: 33415447
DOI: 10.1007/s11864-020-00809-w -
PLoS Computational Biology Dec 2020The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus poses serious threats to the global public health and leads to worldwide crisis. No...
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus poses serious threats to the global public health and leads to worldwide crisis. No effective drug or vaccine is readily available. The viral RNA-dependent RNA polymerase (RdRp) is a promising therapeutic target. A hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected market available drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008μM and 9.453 μM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of fast and accurate anti-viral drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.
Topics: Aminopterin; Animals; Antiviral Agents; Azithromycin; Chlorocebus aethiops; Computer Simulation; Deep Learning; Drug Evaluation, Preclinical; Drug Repositioning; Molecular Dynamics Simulation; RNA-Dependent RNA Polymerase; SARS-CoV-2; Vero Cells; Virus Replication; COVID-19 Drug Treatment
PubMed: 33382685
DOI: 10.1371/journal.pcbi.1008489