Hematological Oncology最新文献

{"title":"Treatment-free remission as a new goal in the management of chronic myeloid leukemia: Clinical and biological aspects","authors":"Daniele Cattaneo,&nbsp;Cristina Bucelli,&nbsp;Valentina Bellani,&nbsp;Barbara Mora,&nbsp;Alessandra Iurlo","doi":"10.1002/hon.3309","DOIUrl":"https://doi.org/10.1002/hon.3309","url":null,"abstract":"<p>The therapeutic armamentarium of chronic myeloid leukemia (CML) has dramatically improved after small molecule tyrosine kinase inhibitors (TKIs) targeting <i>BCR::ABL1</i> became available, with a life expectancy now close to that of the general population. Although highly effective, these drugs also have a toxicity profile that is often mild to moderate, but sometimes severe. Indeed, long-term treatment with TKIs can lead to chronic adverse events that can negatively affect patients' quality of life and can promote significant morbidity and mortality, particularly in the case of second- or third-generation TKIs. Treatment discontinuation has therefore become an emerging goal for CML patients and numerous studies have evaluated in off-TKI subjects what requirements are appropriate for an attempt at treatment-free remission (TFR). TFR eligibility is currently limited to a small population of subjects with both deep and sustained molecular responses to TKIs. For those attempting TFR, average success rates are promising, with 25%–30% of patients experiencing prolonged TFR. In case of failure to maintain sustained TFR, safety results to date are reassuring, with almost all patients responding successfully to resumption of TKIs, and advanced-phase disease progression representing a very rare event. The purpose of this review is to discuss guidelines for TKI discontinuation, clinical advances from clinical trials and real-life experiences, and describe areas of research, particularly regarding the biological factors capable of predicting the success of TFR.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bruton tyrosine kinase inhibitor monotherapy in B-cell lymphoma and risk of infection: A systematic review and meta-analysis of randomized controlled trials","authors":"Mohammed Zuber,&nbsp;Samruddhi Nandkumar Borate,&nbsp;Pooja Gokhale,&nbsp;Akhila Yerubandi,&nbsp;N. M. Mahmudul Alam Bhuiya,&nbsp;Smita Rawal,&nbsp;Henry N. Young,&nbsp;Lorenzo Villa Zapata","doi":"10.1002/hon.3308","DOIUrl":"https://doi.org/10.1002/hon.3308","url":null,"abstract":"<p>Bruton's tyrosine kinase (BTK) inhibitors are important therapeutic advances with promising efficacy outcomes in the treatment of patients with chronic lymphocytic leukemia and other B-cell lymphoma subtypes. However, the utility of BTK inhibitors can be limited by adverse events such as infections. In this systematic review and meta-analysis, we aim to determine the risk of various infections associated with BTK inhibitor monotherapy in B-cell lymphoma patients. A comprehensive search was conducted in MEDLINE/PubMed, Embase, and Web of Science databases from their inception until October 2023. ClinicalTrials.gov, bibliographies, and relevant conference abstracts were also searched for additional records. Randomized controlled trials that included any B-cell lymphoma patients treated with BTK inhibitor monotherapy and reported infection were included. Meta-analysis was performed to calculate risk ratio (RR) using a random-effects model in <i>R</i> Statistical Software, version 4.3.2. Of 3292 studies retrieved, we included 12 studies in this systematic review and meta-analysis. The median age of patients across the study arms ranged between 64 and 73 years. The overall pooled RR for any grade upper respiratory tract infections (URTI) associated with BTK inhibitor treatment was 1.55 (95% Confidence Interval (CI) 1.22–1.97). The RR of grade ≥3 URTI was reported in 14 out of 1046 patients, yielding an RR of 1.46 (95% CI 0.61–3.54), which was not statistically significant. The pooled RR of any grade pneumonia was 1.20 (95% CI 0.68–2.10) and grade ≥3 pneumonia was 1.12 (95% CI 0.67–1.85), both of which were not statistically significant. Patients with B-cell lymphoma who are undergoing BTK inhibitor monotherapy face an elevated risk of developing URTI. Clinicians prescribing BTK inhibitors should be aware of the potential infectious events that may occur. Close monitoring and the implementation of effective prophylactic measures are essential for managing these patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on the mechanism of HOPX-HDAC2 interaction inducing differentiation blockage in acute myeloid leukemia","authors":"Fang He,&nbsp;Yan Tu,&nbsp;Lihong Ni","doi":"10.1002/hon.3307","DOIUrl":"10.1002/hon.3307","url":null,"abstract":"<p>Homeodomain-only protein homeobox (<i>HOPX</i>) mainly exerts its transcriptional repression by physically sequestering the serum co-repressor and recruiting histone deacetylase (<i>HDAC</i>), possessing important potential as a prognostic gene in acute myeloid leukemia (AML). <i>HDACs</i> play crucial roles in cell growth, gene regulation, and metabolism, and they are also important factors in promoting AML progression. Therefore, this project attempts to investigate whether <i>HOPX</i> affects AML progression by interacting with <i>HDAC2</i> protein. Bioinformatics analysis was employed to identify potential prognostic genes in AML. Flow cytometry and MTT assays were performed to analyze the cellular biological functions of the AML prognostic marker <i>HOPX</i>. The interaction network of <i>HOPX</i> was analyzed using the Search Tool for the Retrieval of Interacting Genes database, and the interaction between <i>HOPX</i> and <i>HDAC2</i> was observed using endogenous and exogenous immunoprecipitation. <i>HOPX</i> is highly expressed in AML cells. Further research uncovered that low expression of <i>HOPX</i> can repress the proliferation activity, anti-apoptotic ability, and differentiation blockage of AML cells. Moreover, mechanistically, <i>HOPX</i> induced AML differentiation blockage and malignant progression through interaction with HDAC. <i>HOPX</i> can serve as a prognostic marker for AML and can interact with <i>HDAC2</i> to induce AML differentiation blockage and malignant progression.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined targeting of Hedgehog/GLI1 and Wnt/β-catenin pathways in mantle cell lymphoma","authors":"Yan Han,&nbsp;Chuntuan Li,&nbsp;Shengquan Liu,&nbsp;Jingjing Gao,&nbsp;Yanjun He,&nbsp;Huifang Xiao,&nbsp;Qi Chen,&nbsp;Yan Zheng,&nbsp;Hongyuan Chen,&nbsp;Xiongpeng Zhu","doi":"10.1002/hon.3305","DOIUrl":"https://doi.org/10.1002/hon.3305","url":null,"abstract":"<p>Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma. Challenges in its treatment include relapse, drug resistance, and a short survival period. The Hedgehog/GLI1 (Hh/GLI1) and Wnt/β-catenin pathways are crucial in cancer cell proliferation, survival, and drug resistance, making them significant targets for anticancer research. This study aimed to assess the effectiveness of combining inhibitors for both pathways against MCL and investigate the underlying molecular mechanisms. The co-expression of key proteins from the Hh/GLI1 and Wnt/β-catenin pathways was observed in MCL. Targeting the Hh/GLI1 pathway with the GLI1 inhibitor GANT61 and the Wnt/β-catenin pathway with the CBP/β-catenin transcription inhibitor ICG-001, dual-target therapy was demonstrated to synergistically suppressed the activity of MCL cells. This approach promoted MCL cell apoptosis, induced G0/G1 phase blockade, decreased the percentage of S-phase cells, and enhanced the sensitivity of MCL cells to the drugs adriamycin and ibrutinib. Both GANT61 and ICG-001 downregulated GLI1 and β-catenin while upregulating GSK-3β expression. The interaction between Hh/GLI1 and Wnt/β-catenin pathways was mediated by GANT61-dependent Hh/GLI1 inhibition. Moreover, GLI1 knockdown combined with ICG-001 synergistically induced apoptosis and increased drug sensitivity of MCL cells to doxorubicin and ibrutinib. GANT61 attenuated the overexpression of β-catenin and decreased the inhibition of GSK-3β in MCL cells. Overall, the combined targeting of both the Hh/GLI1 and Wnt/β-catenin pathways was more effective in suppressing proliferation, inducing G0/G1 cycle retardation, promoting apoptosis, and increasing drug sensitivity of MCL cells than mono treatments. These findings emphasize the potential of combinatorial therapy for treating MCL patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics, outcomes and health care utilization of patients with acute myeloid leukemia aged 70 years or older: A single-center retrospective analysis","authors":"Marie Anne-Catherine Neumann,&nbsp;Jan-Hendrik Naendrup,&nbsp;Jorge Garcia Borrega,&nbsp;Ismini Halmer,&nbsp;Lisa Altenrath,&nbsp;Noelle Sieg,&nbsp;Michael Hallek,&nbsp;Dennis A. Eichenauer,&nbsp;Jan-Michel Heger","doi":"10.1002/hon.3300","DOIUrl":"10.1002/hon.3300","url":null,"abstract":"<p>The overall prognosis of older patients with acute myeloid leukemia (AML) is dismal. Only a small subgroup experiences long-term survival. The discrimination between patients who are candidates for potentially curative approaches and those who are not is crucial since - in addition to differences in terms of AML-directed treatment - different policies concerning intensive care unit (ICU) admission and involvement of specialized palliative care (SPC) seem obvious. To shed more light on characteristics, outcomes and health care utilization of older individuals with AML, we conducted an analysis comprising 107 consecutive patients with newly diagnosed AML aged ≥70 years treated at an academic tertiary care center in Germany between 1 January 2015, and 31 December 2020. Median age was 75 years (range: 70–87 years); 45% of patients were female. The proportion of patients receiving intensive induction chemotherapy was 35%, 55% had low-intensity treatment and 10% did not receive AML-directed treatment or follow-up ended before treatment initiation. At least one ICU admission was documented for 47% of patients; SPC was involved in 43% of cases. Median follow-up was 199 days. The median overall survival (OS) was 2.5 months; the 1-year OS rate was 16%. Among patients who died during observation, the median proportion of time spent in the hospital between AML diagnosis and death was 56%. The most common places of death were normal wards (31%) and the ICU (28%). Patients less frequently died in a palliative care unit (14%) or at home (12%). In summary, results of the present analysis confirm the unfavorable prognosis of older patients with AML despite intensive health care utilization. Future efforts in this patient group should aim at optimizing the balance between appropriate AML-directed treatment on the one hand and health care utilization including ICU stays on the other hand.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of escalating therapy with brentuximab vedotin-AVD in advanced stage Hodgkin lymphoma patients with positive interim positron emission tomography after ABVD","authors":"Carmen Martínez,&nbsp;Esther Carcelero,&nbsp;Antonio Gutiérrez,&nbsp;Esther Sancho,&nbsp;Josep Maria Martí-Tutusaus,&nbsp;Laura Magnano,&nbsp;Pablo Mozas,&nbsp;Francesc Fernández-Avilés,&nbsp;María Gabriela Antelo,&nbsp;Xavier Setoain,&nbsp;Sonia Rodríguez,&nbsp;Jordi Esteve","doi":"10.1002/hon.3299","DOIUrl":"10.1002/hon.3299","url":null,"abstract":"<p>Patients with advanced-stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG-PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression-free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification. We report on A-AVD escalation treatment outcomes for 15 iPET-positive patients post-ABVD. Overall response and complete response rates were 80% and 60%, respectively. Four patients underwent salvage therapy followed by autologous stem cell transplantation. At a median 17-month follow-up, all patients are alive, 87% in complete remission, and 1-year PFS was 57.8%. For patients ineligible for BEACOPP due to age, comorbidities, or preference, A-AVD escalation may be a viable alternative.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse impact of 1q amplification on outcomes in patients with multiple myeloma treated with daratumumab, carfilzomib and dexamethasone in a real-world clinical setting","authors":"Taku Kikuchi,&nbsp;Nobuhiro Tsukada,&nbsp;Kodai Kunisada,&nbsp;Chiaki Matsumoto,&nbsp;Moe Nomura-Yogo,&nbsp;Yuki Oda,&nbsp;Kota Sato,&nbsp;Tomomi Takei,&nbsp;Mizuki Ogura,&nbsp;Yu Abe,&nbsp;Kenshi Suzuki,&nbsp;Osamu Hosoya,&nbsp;Tadao Ishida","doi":"10.1002/hon.3306","DOIUrl":"10.1002/hon.3306","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From trials to statistical insights: Bortezomib's story in childhood T-cell lymphoid malignancies","authors":"Shyam Srinivasan","doi":"10.1002/hon.3304","DOIUrl":"10.1002/hon.3304","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and outcome of early-stage diffuse large B cell lymphoma of female genital track: A retrospective study of the Hellenic cooperative lymphoma group","authors":"Evgenia Verrou,&nbsp;Sotirios G. Papageorgiou,&nbsp;Maria Bouzani,&nbsp;Aggeliki Sevastoudi,&nbsp;Theodora Triantafyllou,&nbsp;Aikaterini Daiou,&nbsp;Dimitra Dalampira,&nbsp;Maria Arapaki,&nbsp;Chara Giatra,&nbsp;Anastasia Banti,&nbsp;Gerasimos Kyriakidis,&nbsp;Dionisios Stoumpos,&nbsp;Nikolaos Karampatzakis,&nbsp;Theodosia Papadopoulou,&nbsp;Maria Kotsopoulou,&nbsp;Anastasia Pouli,&nbsp;Evdokia Mandala,&nbsp;Vassiliki Pappa,&nbsp;Emmanouil Spanoudakis,&nbsp;Eirini Katodritou,&nbsp;Theodoros P. Vassilakopoulos","doi":"10.1002/hon.3303","DOIUrl":"10.1002/hon.3303","url":null,"abstract":"<p>Involvement of female genital track (FGT) by diffuse large B cell lymphoma (DLBCL) represents an extremely rare diagnosis. Especially data regarding early-stage disease (i.e., IE, IIE) is very limited. Importantly, previous studies showed controversial results about the risk of central nervous system (CNS) relapse in this entity. Herein, we describe one of the largest reported real-world series of patients with early-stage FGT DLBCL aiming to investigate the clinicopathological characteristics, response to therapy and survival outcomes in the era of immunochemotherapy. We analyzed 21 consecutive patients with biopsy proven DLBCL from uterus or ovary classified as stage IE or IIE out of 1905 newly diagnosed DLBCL patients (1.1%). Uterine and ovarian localization was observed in 14 and seven patients, respectively. Median age was 66 years (range 33–96); 9/21 (43%) were &lt;55 years. Regarding Cell of Origin DLBCL subtype, Germinal Center B-cell subtype was found in seven patients, non-GCB in 10 and non-classified in 4 patients. Median follow-up was 57 months and 5-year overall survival, lymphoma specific survival and Freedom from Progression were 78%, 89% and 90%, respectively. There was no correlation of patients' characteristics with survival parameters. Interestingly, none of the patients experienced CNS relapse. Our results indicate that localized FGT DLBCL exhibits a good prognosis and may not increase the risk for secondary CNS involvement.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of gut microbiome in the outcome of lymphoma patients treated with checkpoint inhibitors—The MicroLinf Study","authors":"Beatrice Casadei,&nbsp;Gabriele Conti,&nbsp;Monica Barone,&nbsp;Silvia Turroni,&nbsp;Serafina Guadagnuolo,&nbsp;Alessandro Broccoli,&nbsp;Patrizia Brigidi,&nbsp;Lisa Argnani,&nbsp;Pier Luigi Zinzani","doi":"10.1002/hon.3301","DOIUrl":"10.1002/hon.3301","url":null,"abstract":"<p>Biomarkers for immune checkpoint inhibitors (ICIs) response and resistance include PD-L1 expression and other environmental factors, among which the gut microbiome (GM) is gaining increasing interest especially in lymphomas. To explore the potential role of GM in this clinical issue, feces of 30 relapsed/refractory lymphoma (Hodgkin and primary mediastinal B-cell lymphoma) patients undergoing ICIs were collected from start to end of treatment (EoT). GM was profiled through Illumina, that is, 16S rRNA sequencing, and subsequently processed through a bioinformatics pipeline. The overall response rate to ICIs was 30.5%, with no association between patients clinical characteristics and response/survival outcomes. Regarding GM, responder patients showed a peculiar significant enrichment of <i>Lachnospira</i>, while non-responder ones showed higher presence of <i>Enterobacteriaceae</i> (at baseline and maintained till EoT). Recognizing patient-related factors that may influence response to ICIs is becoming critical to optimize the treatment pathway of heavily pretreated, young patients with a potentially long-life expectancy. These preliminary results indicate potential early GM signatures of ICIs response in lymphoma, which could pave the way for future research to improve patients prognosis with new adjuvant strategies.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}