Blood and Lymphatic Cancer-Targets and Therapy最新文献

{"title":"Prognostic analysis of CD5 expression in double-hit diffuse large B-cell lymphoma and effectiveness comparison in patients treated with dose-adjusted EPOCH plus rituximab/R-CHOP regimens","authors":"Fangwen Zhang, Ling Li, Lei Zhang, Xin Li, Xiaorui Fu, Xinhua Wang, Jingjing Wu, Zhenchang Sun, Fei Kong, L. Ren, Mingzhi Zhang","doi":"10.2147/BLCTT.S216292","DOIUrl":"https://doi.org/10.2147/BLCTT.S216292","url":null,"abstract":"Objectives To compare the efficacy of rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH-R) with traditional rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) regimens in CD5+ double-hit lymphoma (DHL) and to evaluate prognostic factors. Methods We retrospectively studied 139 patients with newly diagnosed DHL/THL diffuse large B-cell lymphoma (including 20 cases CD5+ and 119 cases CD5−), 87 cases were MYC/BCL2 DHL, 30 cases were MYC/BCL6 DHL, 22 cases were THL. MYC, BCL2 and BCL6 rearrangements were examined by fluorescence in-situ hybridization. CD5 is detected by immunohistochemistry (IHC). Results The objective response rate (ORR) difference between CD5+ and CD5− was significant (80.0% vs 63.8%, P=0.003). The median follow-up time was 18 months (range: 4–39 months). Progression-free survival (PFS) of CD5+ group was significantly worse than that of CD5- (28.1% vs 59.0%, P=0.028), while no significant difference was observed in overall survival (OS) (32.1% vs 59.9%, P=0.057). Compared with the two regimens, the 2-year survival rate of DA-EPOCH-R group was significantly superior than that of R-CHOP (63.6% vs 45.4%, P=0.034 for PFS; 67.4% vs 47.8%, P=0.038 for OS). Besides, CD5+ patients receiving DA-EPOCH-R had survival benefits compared with R-CHOP in PFS (85.7% vs 23.0%, P=0.029), but there was no statistical difference in OS (87.7% vs 34.4.0%, P=0.064). However, in DA-EPOCH-R protocol, there was no significant difference between CD5+ DHL (MYC/BCl2 and MYC/BCL6) and triple-hit lymphoma (P=0.776 for PFS; P=0.728 for OS). Multivariate analysis showed that CD5+ treatment regimen and disease stage were independent prognostic factors. Conclusion Our retrospective study shows that CD5+ has a poorer prognosis than CD5− patients. Based on its improved lifetime and good tolerance on CD5+ patients, which is expected to become the first-line treatment for high-risk DLBCL types based on more clinical research.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"48 1","pages":"33 - 43"},"PeriodicalIF":2.8,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84688760","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":"IDH1-mutated relapsed or refractory AML: current challenges and future prospects","authors":"J. Megías-Vericat, O. Ballesta-López, E. Barragán, P. Montesinos","doi":"10.2147/BLCTT.S177913","DOIUrl":"https://doi.org/10.2147/BLCTT.S177913","url":null,"abstract":"Abstract The prognosis of patients with relapsed or refractory acute myeloid leukemia (R/R AML) is discouraging with salvage standard approaches. Mutations of isocitrate dehydrogenase 1 (IDH1mut), present in 7–14% of AML patients, have been discovered recently, opening the door to targeted agents aiming to improve the outcomes in this setting. Several oral selective IDH1mut inhibitors are under investigation, ivosidenib being the first approved for R/R AML. We performed a systematic review to analyze the clinical outcomes and safety reported with IDH1mut inhibitors and other agents in adult patients with IDH1mut R/R AML. Ivosidenib in monotherapy achieved complete remission (CR) of 24%, overall response of 42%, and median overall survival of 9 months in R/R AML, and promising outcomes were reported with IDH305 and FT-2102. IDH1mut inhibitors were generally well tolerated, but some therapy-related toxicities should be monitored, including IDH-differentiation syndrome, prolongation of the QT interval, and leukocytosis, all manageable and reversible. Also, venetoclax, CB-839, PARP inhibitors, and IDH1 peptide vaccine are being studied in IDH1mut AML. The results of the ongoing and upcoming clinical trials will bring new evidence to establish the role of IDH1mut inhibitors in therapeutic strategies of AML.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"18 1","pages":"19 - 32"},"PeriodicalIF":2.8,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73049269","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":"The expanding role of venetoclax in chronic lymphocytic leukemia and small lymphocytic lymphoma.","authors":"Michael Schieber, Shuo Ma","doi":"10.2147/BLCTT.S177009","DOIUrl":"10.2147/BLCTT.S177009","url":null,"abstract":"<p><p>The BCL-2 protein family members inhibit cellular apoptosis, and their overexpression represents a common survival adaption in cancer. Recently, a selective BCL-2 inhibitor ABT-199, venetoclax, has demonstrated remarkable activity in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), both as a single agent and in combination with anti-CD20 immunotherapies, such as rituximab. In this article, we review the development and latest clinical data that have led to the expanded approval of venetoclax with rituximab in relapsed/refractory CLL/SLL. We also discuss ongoing and future clinical trials designed to evaluate the efficacy of venetoclax in previously untreated patients and to investigate venetoclax combinations with inhibitors of B-cell receptor signaling pathway. These studies hope to offer an expanded list of chemotherapy-free regimens for patients with CLL/SLL.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"9 ","pages":"9-17"},"PeriodicalIF":3.9,"publicationDate":"2019-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/fb/blctt-9-9.PMC6859801.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37601212","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":"Strategies for minimal residual disease detection: current perspectives","authors":"G. Andreani, D. Cilloni","doi":"10.2147/BLCTT.S172693","DOIUrl":"https://doi.org/10.2147/BLCTT.S172693","url":null,"abstract":"Abstract Currently, the post-remission treatment in acute leukemia is based on the genetic profile of leukemic cells at diagnosis (ie, FLT3 ITD positivity) and on the level of measurable residual disease (MRD) after induction and consolidation chemotherapy. Two methods are currently preferred for MRD evaluation in many centers: multiparameter flow cytometry and real-time quantitative PCR. Additional methods such as next-generation sequencing and digital PCR are under investigation, in an attempt to increase the sensitivity and thus allowing the detection of small clones. Many studies suggest that MRD positivity after chemotherapy is associated with negative prognosis, and the reappearance of MRD during follow-up allows impending relapse to be identified and consequently enables early intervention. Finally, MRD positivity before hematopoietic stem cell transplantation is predictive of the outcome. Although the significance of MRD in acute leukemia has been widely explored, the assessment of molecular MRD is not yet a routine practice. In this review, we describe the significance of MRD in different settings and the main markers and methods used for MRD detection.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"60 1","pages":"1 - 8"},"PeriodicalIF":2.8,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80644969","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":"Plasmablastic lymphoma: current perspectives","authors":"Andrés López, P. Abrisqueta","doi":"10.2147/BLCTT.S142814","DOIUrl":"https://doi.org/10.2147/BLCTT.S142814","url":null,"abstract":"Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy with large neoplastic cells, most of them resembling plasmablasts that have a CD20-negative phenotype. Although initially described as being associated with HIV, over the years it has also been identified in patients with solid organ transplant and immunocompetent patients. Little is known about molecular basis that drives PbL, and still its diagnosis remains challenging given its rarity. However, proper recognition of its clinical characteristics, localization, and morphological features can establish a correct diagnosis of PbL within the spectrum of CD20-negative large B-cell lymphomas (LBCLs). PbL is characterized by CD20 and PAX5 negativity together with the expression of CD38, CD138, MUM1/IRF4, Blimp1, and XBP1 plasmacytic differentiation markers. It is usually associated with Epstein–Barr virus infections, and MYC gene rearrangements. PbL should be carefully differentiated from other CD20-negative B-cell neoplasms, ie, primary effusion lymphoma, anaplastic lymphoma kinase-positive (ALK) large B-cell lymphoma, and LBCL in human herpesvirus 8-associated multicentric Castleman disease. Despite our improved understanding of this disease, its prognosis remains dismal with short overall survival. There is no standard of care for this entity. Several chemotherapy combinations have been used with hardly any differences on its outcome. Thus, new approaches with the addition of novel molecules are needed to overcome its poor prognosis. Our current understanding and knowledge of PbL relies primarily on case reports and small case series. In this review, we revise through an extensive literature search, the clinical and biological characteristics of this entity, and the potential therapeutic options.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"24 1","pages":"63 - 70"},"PeriodicalIF":2.8,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85444052","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":"Recent advances in the biology and treatment of B-cell acute lymphoblastic leukemia.","authors":"Mehrdad Hefazi,&nbsp;Mark R Litzow","doi":"10.2147/BLCTT.S170351","DOIUrl":"https://doi.org/10.2147/BLCTT.S170351","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Over the last decade, major advances have been made in our understanding and management of ALL. Identification of new prognostic genomic markers and incorporation of minimal residual diseases' assessment into therapeutic protocols have improved risk stratification and treatment strategies. The use of pediatric-inspired regimens for adolescent and young adults, and the advent of tyrosine kinase inhibitors and novel targeted therapies, including monoclonal antibodies and chimeric antigen receptor T cells, have redefined the therapeutic paradigm of ALL, and significantly improved the outcomes. In this article, we will provide an overview of the current knowledge regarding the biology and treatment of ALL, and highlight recent diagnostic and therapeutic advances made in this area over the past 5 years.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"8 ","pages":"47-61"},"PeriodicalIF":2.8,"publicationDate":"2018-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S170351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215413","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":"Current understanding of the role and regulation of miRNAs in Burkitt lymphoma","authors":"A. Videtta, V. Malagnino, G. De Falco","doi":"10.2147/BLCTT.S129618","DOIUrl":"https://doi.org/10.2147/BLCTT.S129618","url":null,"abstract":"Since its discovery in 1958, Burkitt lymphoma (BL) has been extensively studied and has become a model for tumorigenesis, but its pathogenesis has not been completely explained and understood yet. The aim of this review was to summarize the current knowledge about BL and, in particular, to discuss the role of miRNAs in its pathogenesis and their possible use as diagnostic and prognostic indicators. The impact of viral-encoded miRNAs is also discussed, with the Epstein–Barr infection being almost invariably detected in the endemic variant of this tumor.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"24 1","pages":"33 - 45"},"PeriodicalIF":2.8,"publicationDate":"2018-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88949723","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":"Smoldering multiple myeloma: prevalence and current evidence guiding treatment decisions","authors":"Agnieszka Blum, D. Bazou, P. O’gorman","doi":"10.2147/BLCTT.S136447","DOIUrl":"https://doi.org/10.2147/BLCTT.S136447","url":null,"abstract":"Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder associated with risk of progression to symptomatic multiple myeloma (MM) or amyloidosis. In comparison to monoclonal gammopathy of undetermined significance (MGUS), SMM has a much higher risk of progression to MM. Thanks to advances in our understanding of the risk factors, the subset of patients with ultra-high risk of progression to MM (80%–90% at 2 years) has been identified. The revision of the diagnostic criteria resulted in changes in the management of this cohort of patients. In contrast to the management guidelines for MGUS patients, SMM patients need to be studied more intensively in order to identify biomarkers necessary for accurate risk stratification. In this review, we focus on the risk of progression from SMM to MM, as well as the influence of early treatment on overall survival, time to progression and quality of life.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"09 1","pages":"21 - 31"},"PeriodicalIF":2.8,"publicationDate":"2018-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85863321","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":"Outcomes and relapse patterns following chemotherapy in advanced Hodgkin lymphoma in the positron emission tomography era","authors":"C. Lapuz, A. Enjeti, P. O'Brien, A. Capp, E. Holliday, S. Gupta","doi":"10.2147/BLCTT.S160404","DOIUrl":"https://doi.org/10.2147/BLCTT.S160404","url":null,"abstract":"Background This study evaluated relapse patterns and survival in advanced Hodgkin lymphoma (HL) patients treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) with positron emission tomography (PET) used for staging and response assessment. Patients and methods Patients aged 18 years or above with newly diagnosed histologically proven Stage III or IV HL treated with ABVD at Calvary Mater Newcastle from January 2005 to December 2012 were included in this study. All patients underwent pre-chemotherapy staging with 18F-fluorodeoxyglucose PET or PET/computed tomography and post-chemotherapy PET or PET/computed tomography for the assessment of response. Results Forty-three patients were included in the study. The 5-year disease-free survival, progression-free survival and overall survival were 88%, 74% and 86%, respectively. PET complete response was seen in 35 patients (81%), and the 5-year overall survival for this group was 94%. Relapse following a PET complete response was low (three patients) and occurred predominantly at the initial sites of disease. Four of five patients with bulky disease received consolidative radiotherapy and no in-field relapses were observed. Conclusion Advanced stage HL with a PET complete response following ABVD is associated with an excellent prognosis.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"12 1","pages":"13 - 20"},"PeriodicalIF":2.8,"publicationDate":"2018-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85489531","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":"Blastic plasmacytoid dendritic cell neoplasm: challenges and future prospects","authors":"A. Trottier, S. Cerquozzi, C. Owen","doi":"10.2147/BLCTT.S132060","DOIUrl":"https://doi.org/10.2147/BLCTT.S132060","url":null,"abstract":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare CD4+ CD56+ myeloid malignancy that is challenging to diagnose and treat. BPDCN typically presents with nonspecific cutaneous lesions with or without extra-cutaneous manifestations before progressing to leukemia. Currently, there is no standard of care for the treatment of BPDCN and various approaches have been used including acute myeloid leukemia, acute lymphoblastic leukemia, and lymphoma-based regimens with or without stem cell transplantation. Despite these treatment approaches, the prognosis of BPDCN remains poor and there is a lack of prospective data upon which to base treatment decisions. Recent work examining the mutational landscape and gene expression profiles of BPDCN has identified a number of potential therapeutic targets. One such target is CD123, the α subunit of the human interleukin-3 receptor, which is the subject of intervention studies using the novel agent SL-401. Other investigational therapies include UCART123, T-cell immunotherapy, and venetoclax. Prospective trials are needed to determine the best treatment for this uncommon and aggressive neoplasm.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"54 1","pages":"85 - 93"},"PeriodicalIF":2.8,"publicationDate":"2017-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77100760","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}