Blood and Lymphatic Cancer-Targets and Therapy最新文献

{"title":"Successful Anatomy Adapted Therapeutic Management and Genetic Profiling of Primary Pituitary Diffuse Large B-Cell Lymphoma.","authors":"ErinMarie O Kimbrough,&nbsp;Vivek Gupta,&nbsp;Liuyan Jiang,&nbsp;Han W Tun","doi":"10.2147/BLCTT.S420442","DOIUrl":"https://doi.org/10.2147/BLCTT.S420442","url":null,"abstract":"<p><p>Primary pituitary diffuse large B-cell lymphoma (PPL) has been regarded as a subtype of primary central nervous system lymphoma (PCNSL); however, the pituitary gland is located outside the blood brain barrier (BBB) with neural and vascular connections to the brain. Given its unique anatomic location, a combination of non-central nervous system (CNS)-penetrating and CNS-penetrating therapeutic agents can be employed to treat PPL. We report a female patient with PPL who was successfully managed with anatomy-adapted therapy incorporating non-CNS penetrating chemoimmunotherapy [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)] alternating with CNS-penetrating chemoimmunotherapy [rituximab, high-dose methotrexate, and high-dose cytarabine (RMA)]. She received a total of eight cycles of treatment with four cycles of each regimen following partial transsphenoidal resection. She achieved a complete response after two cycles and has remained in complete remission for the last eight years. To our knowledge, this is the longest documented survival in a patient with PPL. Targeted genomic profiling with Next-Generation Sequencing (NGS) was recently performed on the lymphoma tissue. The genomic profile of PPL in this patient is quite different from the findings typically associated with PCNSL. We suggest that PPL may be biologically distinct from PCNSL and should be treated with an anatomy adapted approach. Additional research is necessary to confirm our findings.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"13 ","pages":"25-32"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/74/blctt-13-25.PMC10392811.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PI3k Inhibitors in NHL and CLL: An Unfulfilled Promise.","authors":"Naji Bou Zeid,&nbsp;Victor Yazbeck","doi":"10.2147/BLCTT.S309171","DOIUrl":"https://doi.org/10.2147/BLCTT.S309171","url":null,"abstract":"<p><p>Phosphatidylinositol 3-kinases (PI3Ks) are a family of intracellular signal transducer enzymes that can attach a phosphate group to the 3'-hydroxyl of the inositol moiety of membrane-embedded phosphatidylinositol (PI). PI3Ks have been shown to play important roles in cell proliferation, growth, survival, motility, and metabolism. Nonetheless, the PI3K pathway has also shown to be overactivated in several tumors, particularly B-cell malignancies. In recent years, the PI3K signaling pathway has become the major focus of substantial drug discovery and development efforts. Selective (PI3K) inhibitors have been approved for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and indolent non-Hodgkin lymphomas (iNHL), such as follicular lymphoma and marginal-zone lymphoma. Four selective PI3K inhibitors have received accelerated FDA approvals for the treatment of patients with relapsed/refractory (R/R) CLL and/or iNHL based mainly on single-arm Phase II studies: Idelalisib (PI3K-δ inhibitor), copanlisib (dual PI3K-α and PI3K-δ inhibitor), duvelisib (dual PI3K-γ and PI3K-δ inhibitor), and umbralisib (dual PI3Kδ and CK1ε inhibitor). Conversely, recent interim results of randomized control trials (RCTs) involving some of these agents, showed a worrisome trend of decrease in overall survival (OS), and an increase in fatal and severe adverse effects, in comparison with patients in the control arms. Consequently, the class of PI3K inhibitors came under scrutiny, with an FDA expert panel voting on April 21, 2022, recommending that future FDA approvals of PI3K inhibitors be supported by randomized data, rather than single-arm data only, and further discontinuing the use of almost all the PI3K inhibitors in hematologic malignancies. As we believe further research is needed to help potentialize PI3K inhibitors by improving their safety profiles, this mini-review aims at revisiting the clinical successes, the failures, and the promising aspect of this class of drugs, while presenting possible ways that could benefit its successful development.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"13 ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/5b/blctt-13-1.PMC10008402.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9490956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FLT3 Inhibitors as Maintenance Therapy after Allogeneic Stem-Cell Transplantation.","authors":"Amanda Blackmon, Ibrahim Aldoss, Brian J Ball","doi":"10.2147/BLCTT.S281252","DOIUrl":"10.2147/BLCTT.S281252","url":null,"abstract":"<p><p>Mutations in the <i>FLT3</i> gene are associated with poor prognosis in patients with AML, even after consolidation with allogeneic hematopoietic cell transplantation (alloHCT) in first remission. Treatment failure in <i>FLT3</i>-mutated AML is largely driven by excessive risk of relapse compared to other genetic subtypes, including in patients post-alloHCT. As a result, there is substantial interest in studying posttransplant maintenance therapy in <i>FLT3</i>-mutated AML as an approach to optimize disease control and improve long-term outcomes. Clinical trials utilizing posttransplant FLT3 inhibitors, such as sorafenib and midostaurin, have shown feasibility, safety, and encouraging posttransplant outcomes, and there are ongoing studies using newer-generation tyrosine-kinase inhibitors as posttransplant maintenance therapy. Here, we review the toxicities and efficacy of FLT3 inhibitors as posttransplant maintenance, recommendations on the use of FLT3 inhibitors by international consensus guidelines, and highlight key remaining questions.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"12 ","pages":"137-147"},"PeriodicalIF":3.9,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/89/e0/blctt-12-137.PMC9464008.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9708531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asparaginase in the Treatment of Acute Lymphoblastic Leukemia in Adults: Current Evidence and Place in Therapy","authors":"Krishna R Juluri, Chloe Siu, R. Cassaday","doi":"10.2147/BLCTT.S342052","DOIUrl":"https://doi.org/10.2147/BLCTT.S342052","url":null,"abstract":"Abstract Acute lymphoblastic leukemia (ALL) is a rare hematologic malignancy resulting in the production of abnormal lymphoid precursor cells. Occurring in B-cell and T-cell subtypes, ALL is more common in children, comprising nearly 30% of pediatric malignancies, but also constitutes 1% of adult cancer diagnoses. Outcomes are age-dependent, with five-year overall survival of greater than 90% in children and less than 20% in older adults. L-asparaginase, an enzyme not found in humans, depletes serum levels of L-asparagine. As leukemic cells are unable to synthesize this amino acid, its deprivation results in cell death. The success of asparaginase-containing regimens in the treatment of pediatric ALL, and poor outcomes with conventional cytotoxic regimens in adults, have led to trials of pediatric or pediatric-inspired regimens incorporating asparaginase in the adolescent and young adult (AYA) and adult populations. Initially purified from Escherichia coli, newer formulations of asparaginase have been developed to address short half-life, high immunogenic potential, and manufacturing difficulties. Unfamiliarity with asparaginase use and management of its unique toxicities may result in treatment-decisions that negatively impact outcomes. In this review, we address the current use of asparaginase in the treatment of ALL, with an emphasis on its role in the treatment of adults, key clinical trials, recognition and management of toxicities, and ongoing directions of study.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"07 1","pages":"55 - 79"},"PeriodicalIF":2.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85999624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Survival with Ibrutinib Therapy in Elderly Patients with Newly Diagnosed Primary Central Nervous System Lymphoma","authors":"J. Kuhlman, Muhamad Alhaj Moustafa, Liuyan Jiang, Jing Wang, Vivek Gupta, H. Tun","doi":"10.2147/BLCTT.S360442","DOIUrl":"https://doi.org/10.2147/BLCTT.S360442","url":null,"abstract":"Abstract Primary central nervous system lymphoma (PCNSL) carries a dismal prognosis in elderly patients above 70 years of age with a median overall survival of 6 months. Novel therapeutic agents are urgently needed to improve survival outcomes in this age group. We describe the clinical presentation, diagnostic workup, and treatment outcome in two 80-year-old patients diagnosed with PCNSL who were treated with ibrutinib therapy. Both patients remain in complete remission following treatment with ibrutinib therapy. One patient is currently 4 years and the other is 2 years and 9 months from the time of initial diagnosis. We suggest that ibrutinib therapy has significant therapeutic activity against PCNSL in the newly diagnosed setting and should be evaluated in a clinical trial as part of front-line therapy, especially in elderly patients.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"20 1","pages":"23 - 29"},"PeriodicalIF":2.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73394468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropsychiatric Manifestations of Lymphoma-Associated Cerebral Glucose Hypometabolism Can Be Reversed by Intensive Glucose Supplementation","authors":"Adam M. Kase, Catherine Bullock, Ricardo D. Parrondo, Muhamad Alhaj Moustafa, M. Iqbal, K. Li, Ephraim E. Parent, H. Tun","doi":"10.2147/BLCTT.S353430","DOIUrl":"https://doi.org/10.2147/BLCTT.S353430","url":null,"abstract":"Abstract Cerebral glucose hypometabolism (CGHM) is characterized by diffuse or focal reduction in uptake of glucose by the brain as determined on a FDG PET-CT. We report a case of lymphoma-associated cerebral glucose hypometabolism (LA-CGHM) in a patient with hepatosplenic T-cell lymphoma (HSTCL) whose neuropsychiatric symptoms were resolved with glucose supplementation. PET-CT scan showed diffuse cerebral hypometabolism in addition to focal hypermetabolism in the liver related to lymphomatous involvement. He responded rapidly to infusion of 10% dextrose with complete resolution of neurological symptoms on two separate occasions and was later maintained on oral glucose without relapse. While his neuropsychiatric symptoms improved, his aggressive lymphoma and chemo-refractory disease ultimately led to his demise. We suggest that LA-CGHM can cause neuropsychiatric manifestations which can be reversed by intensive glucose supplementation.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"5 1","pages":"17 - 21"},"PeriodicalIF":2.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74497852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How I Manage Patients with Chronic Myeloid Leukemia (CML): Perspectives from Clinical Practice","authors":"G. S. Guru Murthy","doi":"10.2147/BLCTT.S219160","DOIUrl":"https://doi.org/10.2147/BLCTT.S219160","url":null,"abstract":"Abstract The management of chronic myeloid leukemia (CML) has remarkably changed in the last 20 years with the availability of tyrosine kinase inhibitors (TKI). Most patients with chronic phase CML now have a life expectancy like that of age matched controls. Understanding the practical aspects of choosing the appropriate TKI, monitoring response and side-effects are key to long term success. Currently, treatment cessation is also an option in patients achieving sustained deep molecular response. Novel agents are needed in patients with lack of response to TKI and in those with advanced disease.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"104 1","pages":"1 - 6"},"PeriodicalIF":2.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75987171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Value of Measurable Residual Disease in Acute Lymphoblastic Leukemia","authors":"K. Hein, N. Short, E. Jabbour, M. Yilmaz","doi":"10.2147/BLCTT.S270134","DOIUrl":"https://doi.org/10.2147/BLCTT.S270134","url":null,"abstract":"Abstract Measurable (minimal) residual disease (MRD) status in acute lymphoblastic leukemia (ALL) has largely superseded the importance of traditional risk factors for ALL, such as baseline white blood cell count, cytogenetics, and immunophenotype, and has emerged as the most powerful independent prognostic predictor. The development of sensitive MRD techniques, such as multicolor flow cytometry (MFC), quantitative polymerase chain reaction (PCR), and next-generation sequencing (NGS), may further improve risk stratification and expand its impact in therapy. Additionally, the availability of highly effective agents for MRD eradication, such as blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T-cell therapies, enabled the development of frontline regimens capable of eradicating MRD early in the treatment course. While long-term follow-up of this approach is lacking, it has the potential to significantly reduce the need for intensive post-remission treatments, including allogeneic bone marrow transplantation, in a significant proportion of patients with ALL.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"66 1","pages":"7 - 16"},"PeriodicalIF":2.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91233261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges.","authors":"Matthew J Rendo,&nbsp;Jacinth J Joseph,&nbsp;Liem Minh Phan,&nbsp;Christin B DeStefano","doi":"10.2147/BLCTT.S327016","DOIUrl":"https://doi.org/10.2147/BLCTT.S327016","url":null,"abstract":"<p><p>The therapeutic landscape of multiple myeloma (MM) has benefited from an emergence of novel therapies over the last decade. By inducing T-cell kill of target cancer cells, chimeric antigen receptor (CAR) T-cell therapies have improved outcomes of patients with hematologic malignancies. B-cell maturation antigen (BCMA) is the current target antigen of choice for most CAR T-cell products under investigation for MM. However, their shortcomings deal with logistical and clinical challenges, including limited availability, manufacturing times, and toxicities. This article provides an overview of recently developed and investigational CAR T-cell therapies for MM, highlighting current evidence and challenges.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"12 ","pages":"119-136"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/88/da/blctt-12-119.PMC9439649.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10254812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Diagnosis of Waldenström's Macroglobulinemia and Early Management: Perspectives from Clinical Practice.","authors":"Shashank Cingam,&nbsp;Surbhi Sidana","doi":"10.2147/BLCTT.S259860","DOIUrl":"https://doi.org/10.2147/BLCTT.S259860","url":null,"abstract":"<p><p>Waldenström's Macroglobulinemia (WM) is a clonal B-lymphocyte neoplasm characterized by the presence of IgM monoclonal protein and ≥10% bone marrow involvement with lymphoplasmacytic cells. Several mature B-cell and plasma cell disorders can potentially produce monoclonal IgM immunoglobulin and hence, careful consideration of the differential diagnosis is vital. Clinico-pathological features, immunophenotype, and MYD88 mutation status help distinguish WM from other plasma cell and lymphoproliferative disorders. Treatment is only indicated in patients symptomatic from adenopathy or organomegaly, neuropathy, hyper viscosity, cryoglobulinemia, cold agglutinin disease, cytopenia's or amyloidosis. Alkylators (cyclophosphamide, bendamustine) in combination with anti-CD20 antibodies and novel targeted agents including Bruton tyrosine kinase (BTK) inhibitors like ibrutinib are the mainstay of frontline treatment in symptomatic WM.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"12 ","pages":"107-117"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/00/87/blctt-12-107.PMC9394652.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9127713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}