Blood and Lymphatic Cancer-Targets and Therapy最新文献

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Highly Curative Treatment of High-Risk Acute Promyelocytic Leukemia: Induction and Consolidation with ATRA+ATO+anthracyclines and Maintenance with ATRA+RIF. 高风险急性早幼粒细胞白血病的高度治愈性治疗:ATRA+ATO+蒽环类药物的诱导和巩固治疗以及ATRA+RIF的维持治疗。
IF 3.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2024-07-29 eCollection Date: 2024-01-01 DOI: 10.2147/BLCTT.S473984
Dan Liu, Juan Tong, Erling Chen, Li Wang, Lei Xue, Xuhan Zhang, Na Zhao, Xing Hu, Changcheng Zheng
{"title":"Highly Curative Treatment of High-Risk Acute Promyelocytic Leukemia: Induction and Consolidation with ATRA+ATO+anthracyclines and Maintenance with ATRA+RIF.","authors":"Dan Liu, Juan Tong, Erling Chen, Li Wang, Lei Xue, Xuhan Zhang, Na Zhao, Xing Hu, Changcheng Zheng","doi":"10.2147/BLCTT.S473984","DOIUrl":"10.2147/BLCTT.S473984","url":null,"abstract":"<p><strong>Background: </strong>The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-<i>Indigo naturalis</i> formula (RIF) for high-risk APL.</p><p><strong>Methods: </strong>Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs).</p><p><strong>Results: </strong>After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16-44) and 40 days (range: 22-75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9-91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25-142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively.</p><p><strong>Conclusion: </strong>For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890299","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}
引用次数: 0
Albumin-to-Globulin Ratio Combined with Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor in Multiple Myeloma with Renal Impairment. 白蛋白与球蛋白比值结合中性粒细胞与淋巴细胞比值作为肾功能受损的多发性骨髓瘤的预后预测指标
IF 3.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2024-07-02 eCollection Date: 2024-01-01 DOI: 10.2147/BLCTT.S468836
Yingzi Zhang, Xiajuan Yao, Yaoquan Zhang, Zhuyun Chen, Zhongke Qin, Ying Cai, Wenkai Xia, Hong Hu
{"title":"Albumin-to-Globulin Ratio Combined with Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor in Multiple Myeloma with Renal Impairment.","authors":"Yingzi Zhang, Xiajuan Yao, Yaoquan Zhang, Zhuyun Chen, Zhongke Qin, Ying Cai, Wenkai Xia, Hong Hu","doi":"10.2147/BLCTT.S468836","DOIUrl":"10.2147/BLCTT.S468836","url":null,"abstract":"<p><strong>Background: </strong>The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI).</p><p><strong>Methods: </strong>From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index).</p><p><strong>Results: </strong>The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI.</p><p><strong>Conclusion: </strong>ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555652","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}
引用次数: 0
Refractory Burkitt Lymphoma: Diagnosis and Interventional Strategies. 难治性伯基特淋巴瘤:诊断和干预策略。
IF 2.8
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2024-03-13 eCollection Date: 2024-01-01 DOI: 10.2147/BLCTT.S407804
Francesco Malfona, Anna Maria Testi, Sabina Chiaretti, Maria Luisa Moleti
{"title":"Refractory Burkitt Lymphoma: Diagnosis and Interventional Strategies.","authors":"Francesco Malfona, Anna Maria Testi, Sabina Chiaretti, Maria Luisa Moleti","doi":"10.2147/BLCTT.S407804","DOIUrl":"10.2147/BLCTT.S407804","url":null,"abstract":"<p><p>Despite excellent results in frontline therapy, particularly in pediatric age, refractory Burkitt lymphoma still remains a therapeutic challenge, with dismal outcome. The prognosis is very poor, ranging from less than 10% to 30-40%, with longer survival only in transplanted patients. On account of the paucity of data, mostly reporting on small series of patients, with heterogeneous characteristics and salvage treatments, at present it is impossible to draw definitive conclusions on the treatment of choice for this difficult to treat subset of patients. New insights into Burkitt lymphoma/leukemia cell biology have led to the development of new drugs, currently being tested, directed at different specific targets. Herein, we describe the results so far reported in refractory Burkitt lymphoma/leukemia, with standard treatments and hematopoietic stem cell transplant, and we review the new targeted drugs currently under evaluation.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176986","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}
引用次数: 0
Polycythemia Vera: Barriers to and Strategies for Optimal Management. 多血细胞瘤:优化管理的障碍和策略。
IF 2.8
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2023-12-21 eCollection Date: 2023-01-01 DOI: 10.2147/BLCTT.S409443
Andrea Duminuco, Patrick Harrington, Claire Harrison, Natalia Curto-Garcia
{"title":"Polycythemia Vera: Barriers to and Strategies for Optimal Management.","authors":"Andrea Duminuco, Patrick Harrington, Claire Harrison, Natalia Curto-Garcia","doi":"10.2147/BLCTT.S409443","DOIUrl":"10.2147/BLCTT.S409443","url":null,"abstract":"<p><p>Polycythemia vera (PV) is a subtype of myeloproliferative neoplasms characterized by impaired quality of life and severe complications. Despite the increasingly in-depth knowledge of this condition, it necessitates a multifaceted management approach to mitigate symptoms and prevent thrombotic and hemorrhagic events, ensuring prolonged survival. The therapeutic landscape has been revolutionized in recent years, where venesection and hydroxycarbamide associated with antiplatelet therapy have a central role and are now accompanied by other drugs, such as interferon and Janus kinase inhibitors. Ongoing research and advancements in targeted therapies hold promise for further enhancing the therapeutic choice for PV management.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139038007","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}
引用次数: 0
Zanubrutinib in Mantle Cell Lymphoma Management: A Comprehensive Review. 扎鲁替尼在套细胞淋巴瘤治疗中的应用综述。
IF 2.8
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2023-11-24 eCollection Date: 2023-01-01 DOI: 10.2147/BLCTT.S426588
Nada Alsuhebany, Congshan Pan, Eileen Holovac, Brian Do, Ali McBride
{"title":"Zanubrutinib in Mantle Cell Lymphoma Management: A Comprehensive Review.","authors":"Nada Alsuhebany, Congshan Pan, Eileen Holovac, Brian Do, Ali McBride","doi":"10.2147/BLCTT.S426588","DOIUrl":"10.2147/BLCTT.S426588","url":null,"abstract":"<p><strong>Purpose: </strong>The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of zanbrutinib are described.</p><p><strong>Summary: </strong>Mantle cell lymphoma (MCL) is a mature B-cell lymphoma that is typically associated with unfavorable outcomes, and virtually all patients with MCL have refractory or relapsed disease despite aggressive treatment. The treatment paradigm for MCL has transformed dramatically over the past decade owing to rapid advancements in immunotherapy and molecular-targeted therapies. Zanubrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKI) designated for mature B-cell non-Hodgkin's lymphoma (NHL), has drastically improved the survival outcomes in relapsed/refractory (R/R) MCL patients. This selective BTKI is a small molecule that functions by forming a covalent bond in the active site of BTK. The inhibition of BTK activity is essential for the signaling of B-cell antigen receptor (BCR) and cytokine receptor pathways. In a preclinical study, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth. Zanubrutinib was granted FDA-accelerated approval based on the results of Phase I and II trials. The investigator-assessed overall response rate was 83.7%, of which 78% of patients achieved complete response. The median duration of response was 19.5 months, and the median progression-free survival was 22.1 months. The most common (≥20%) all-grade adverse events were low neutrophil count (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), low white blood cell count (33.7%), and low platelet count (32.6%).</p><p><strong>Conclusion: </strong>Zanubrutinib is a selective, next-generation, orally active, irreversible BTK inhibitor. The selectivity of zanubrutinib and its superior efficacy, with a well-tolerated safety profile, have proven to be attractive options for other malignancies.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463290","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}
引用次数: 0
90Yttrium Ibritumomab Tiuxetan (Zevalin) for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Report of 5 Cases. 90伊曲莫单抗提昔坦治疗慢性淋巴细胞白血病/小淋巴细胞淋巴瘤5例报告。
IF 2.8
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2023-10-03 eCollection Date: 2023-01-01 DOI: 10.2147/BLCTT.S398809
Jing Wang, Firas Baidoun, Han W Tun, Muhamad Alhaj Moustafa
{"title":"<sup>90</sup>Yttrium Ibritumomab Tiuxetan (Zevalin) for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Report of 5 Cases.","authors":"Jing Wang,&nbsp;Firas Baidoun,&nbsp;Han W Tun,&nbsp;Muhamad Alhaj Moustafa","doi":"10.2147/BLCTT.S398809","DOIUrl":"10.2147/BLCTT.S398809","url":null,"abstract":"<p><p>Radioimmunotherapy (RIT) with radio-labeled monoclonal antibodies to CD20 produces a high response rate in patients with low-grade B-cell lymphomas. The use of this modality in patients with chronic lymphocytic leukemia (CLL) has been sporadic in clinical trials and was hampered by the extensive marrow involvement seen commonly in patients with CLL, which would produce a high risk for marrow aplasia after treatment with RIT. Herein, we report our experience with RIT in 5 patients with CLL or SLL showing short-lived responses and significant myelosuppression. After 90Y-ibritumomab tiuxetan treatment, the median time to relapse was 65 days, and no cases of MDS or AML were observed during follow-up. All patients experienced grade ≥3 thrombocytopenia and neutropenia, with median durations of 39.5 days and 107 days, respectively.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/15/c4/blctt-13-59.PMC10559791.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154934","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}
引用次数: 0
Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article. 多发性骨髓瘤的鉴别诊断和治疗进展:一篇综述文章。
IF 2.8
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2023-09-15 eCollection Date: 2023-01-01 DOI: 10.2147/BLCTT.S272703
Munawwar Hussain, Sarvari Yellapragada, Samer Al Hadidi
{"title":"Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article.","authors":"Munawwar Hussain,&nbsp;Sarvari Yellapragada,&nbsp;Samer Al Hadidi","doi":"10.2147/BLCTT.S272703","DOIUrl":"https://doi.org/10.2147/BLCTT.S272703","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a hematologic malignancy characterized by the abnormal clonal proliferation of plasma cells that may result in focal bone lesions, renal failure, anemia, and/or hypercalcemia. Recently, the diagnosis and treatment of MM have evolved due to a better understanding of disease pathophysiology, improved risk stratification, and new treatments. The incorporation of new drugs, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and high-dose chemotherapy followed by hematopoietic stem cell transplantation, has resulted in a significant improvement in patient outcomes and QoL. In this review, we summarize differential diagnoses and therapeutic advances in MM.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/62/blctt-13-33.PMC10508231.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159979","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}
引用次数: 0
Human Immunodeficiency Virus Related Non-Hodgkin's Lymphoma. 人类免疫缺陷病毒相关的非霍奇金淋巴瘤。
IF 2.8
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/BLCTT.S407086
Tesfaye Gessese, Fikir Asrie, Zewudu Mulatie
{"title":"Human Immunodeficiency Virus Related Non-Hodgkin's Lymphoma.","authors":"Tesfaye Gessese,&nbsp;Fikir Asrie,&nbsp;Zewudu Mulatie","doi":"10.2147/BLCTT.S407086","DOIUrl":"https://doi.org/10.2147/BLCTT.S407086","url":null,"abstract":"<p><p>Human immunodeficiency virus infection is related with an increased risk of hematological malignancy principally, non-Hodgkin lymphoma. Most non-Hodgkin lymphomas are acquired immunodeficiency syndrome defining and constitute greater than 50% of all acquired immunodeficiency syndrome defining cancers. The main pathogenesis mechanisms are immunodeficiency, chronic antigenic stimulation, and the ability to infect cancer cells causing direct carcinogenesis. Human immunodeficiency virus related non-Hodgkin lymphomas are heterogeneous in immunophenotyping and molecular features; and choice of drug treatments is similar with sporadic types. The main objective is to assess the epidemiology, pathogenesis, and morphology of human immunodeficiency virus related non-Hodgkin lymphoma. The searching strategy was done by searching relevant original and review articles from www.biosemanticjane/org, Google scholar, Google, and PubMed sites using keywords like; Acquired immunodeficiency syndrome, Human immunodeficiency virus, and non-Hodgkin lymphoma. In conclusion, human immunodeficiency virus infected people continue to have elevated risk of non-Hodgkin lymphoma. Diffuse large B-cell lymphomas are the most common and severe subtype. The pathogenesis of this type of lymphoma is associated with chromosomal abnormalities that deregulate the expression of various oncogenes by different viral particles and cytokines. However, the role of these viral particles and cytokines on pathogenesis is not clearly stated, so further study could be required.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"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/1a/8a/blctt-13-13.PMC10237187.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9584938","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}
引用次数: 1
Successful Anatomy Adapted Therapeutic Management and Genetic Profiling of Primary Pituitary Diffuse Large B-Cell Lymphoma. 原发性垂体弥漫性大b细胞淋巴瘤的成功解剖适应治疗管理和遗传谱分析。
IF 2.8
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/BLCTT.S420442
ErinMarie O Kimbrough, Vivek Gupta, Liuyan Jiang, Han W Tun
{"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":null,"pages":null},"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}
引用次数: 0
PI3k Inhibitors in NHL and CLL: An Unfulfilled Promise. NHL和CLL中的PI3k抑制剂:一个未实现的承诺。
IF 2.8
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/BLCTT.S309171
Naji Bou Zeid, Victor Yazbeck
{"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":null,"pages":null},"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}
引用次数: 2
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