Blood Neoplasia最新文献

Lenalidomide, ixazomib, or daratumumab maintenance therapy in multiple myeloma 多发性骨髓瘤的来那度胺、伊沙佐米或达拉曲单抗维持疗法

Blood Neoplasia Pub Date : 2024-09-16 DOI: 10.1016/j.bneo.2024.100042

{"title":"Lenalidomide, ixazomib, or daratumumab maintenance therapy in multiple myeloma","authors":"","doi":"10.1016/j.bneo.2024.100042","DOIUrl":"10.1016/j.bneo.2024.100042","url":null,"abstract":"<div><h3>Abstract</h3><div>Lenalidomide, ixazomib, and daratumumab have been proposed as maintenance therapies for patients with newly diagnosed multiple myeloma (MM; NDMM). There are, however, no randomized controlled trials (RCTs) comparing them. We conducted a network meta-analysis (NMA) of RCTs comparing these agents against placebo in NDMM. A Bayesian NMA model was used to assess the relative effects of competing treatments on progression-free survival (PFS) and overall survival (OS) in 9 studies including 4115 patients with transplant-eligible MM (TEMM) and 1689 patients with non–transplant-eligible MM (NTEMM). Lenalidomide and daratumumab but not ixazomib were associated with improved PFS compared with placebo in patients with TEMM (lenalidomide [hazard ratio (HR), 0.46; 95% credible interval (CrI), 0.36-0.56]; daratumumab [HR, 0.49; 95% Crl, 0.32-0.76]; and ixazomib [HR, 0.72; 95% CrI, 0.46-1.12]) and those with NTEMM (lenalidomide [HR, 0.46; 95% CrI, 0.29-0.75] and ixazomib [HR, 0.69; 95% CrI, 0.43-1.18]). The PFS benefit for daratumumab was present regardless of whether daratumumab-based induction therapy was received. None of the agents showed an OS benefit, and PFS benefits were not seen in patients with high-risk cytogenetics. Lenalidomide was associated with second malignancies, ixazomib with thrombocytopenia, and daratumumab with pneumonia. We propose that lenalidomide remains the maintenance therapy of choice for NDMM.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573253","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

BIRC5 upregulation enhances DNMT3A-mutant T-ALL cell survival and pathogenesis BIRC5 上调可提高 DNMT3A 突变 T-ALL 细胞的存活率和发病率

Blood Neoplasia Pub Date : 2024-09-05 DOI: 10.1016/j.bneo.2024.100040

{"title":"BIRC5 upregulation enhances DNMT3A-mutant T-ALL cell survival and pathogenesis","authors":"","doi":"10.1016/j.bneo.2024.100040","DOIUrl":"10.1016/j.bneo.2024.100040","url":null,"abstract":"<div><h3>Abstract</h3><div>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm. Although the prognosis of pediatric T-ALL has improved with intensified chemotherapy regimens, this benefit has largely not translated to the adult T-ALL population. Development of new treatments requires understanding the mechanisms driven by specific mutations. <em>DNMT3A</em> mutations are identified in ∼10% to 18% of adult patients with T-ALL and are associated with poor clinical outcomes. Here, using primary human specimens, we show that cells from patients with T-ALL with <em>DNMT3A</em> mutations are resistant to apoptosis and certain chemotherapies. Elevated JAK/STAT signaling drove prosurvival programs in patients with mutant <em>DNMT3A</em>, and JAK/STAT inhibition restored sensitivity to chemotherapy. The prosurvival gene <em>BIRC5</em> was upregulated in patients with <em>DNMT3A</em>-mutant T-ALL, and these cells were specifically sensitive to the Baculoviral IAP Repeat Containing 5 (BIRC5) inhibitor YM155. Genetic inhibition of <em>BIRC5</em> in vivo lead to rapid depletion of <em>DNMT3A</em>-mutant T-ALL cells in patient-derived xenografts, positioning BIRC5 as a precision medicine target for these patients.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442796","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

Ibrutinib and venetoclax in combination for chronic lymphocytic leukemia: synergy in practice 伊布替尼和 venetoclax 联合治疗慢性淋巴细胞白血病：实践中的协同作用

Blood Neoplasia Pub Date : 2024-09-01 DOI: 10.1016/j.bneo.2024.100034

{"title":"Ibrutinib and venetoclax in combination for chronic lymphocytic leukemia: synergy in practice","authors":"","doi":"10.1016/j.bneo.2024.100034","DOIUrl":"10.1016/j.bneo.2024.100034","url":null,"abstract":"<div><h3>Abstract</h3><p>The combination of ibrutinib and venetoclax has emerged as a promising therapeutic strategy for patients with chronic lymphocytic leukemia (CLL). Preclinical investigations demonstrated a synergistic antitumor effect through multiple mechanisms, providing a robust foundation for translating this regimen into clinical trials. Beyond the dual inhibition by 2 small molecules, another innovative concept being tested with this combination is the use of measurable residual disease (MRD)–driven treatment vs fixed-duration treatment to meet the escalating demand for oral, convenient, cost-effective, and time-limited therapeutic approaches. The clinical translation of this combination has yielded remarkable outcomes with significant improvements in the progression-free survival and overall survival rates for both treatment-naïve patients and those with relapsed/refractory CLL. Notably, a substantial proportion of patients achieved undetectable MRD. Clinical trial updates following the initial published results have shown consistency and durability of responses over time. In this review, the initial investigator-initiated trial results for ibrutinib and venetoclax are discussed, several multicenter clinical trial designs and outcomes are examined, variables such as chromosome 17p deletion that influence treatment responses are addressed, and the safety of the regimen is discussed. In addition, we reviewed the usage of this combination in other B-cell malignancies and discussed how current knowledge can be used for shaping the future CLL treatment regimens.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000347/pdfft?md5=6d685af44e4971629738466491360299&pid=1-s2.0-S2950328024000347-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095128","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

Augmented use of L-asparaginase markedly improves AYA ALL outcomes: FBMTG prospective MRD2014 study 加强使用 L-天冬酰胺酶可显著改善 AYA ALL 的预后：FBMTG前瞻性MRD2014研究

Blood Neoplasia Pub Date : 2024-09-01 DOI: 10.1016/j.bneo.2024.100033

{"title":"Augmented use of L-asparaginase markedly improves AYA ALL outcomes: FBMTG prospective MRD2014 study","authors":"","doi":"10.1016/j.bneo.2024.100033","DOIUrl":"10.1016/j.bneo.2024.100033","url":null,"abstract":"<div><h3>Abstract</h3><p>The enhanced utilization of native L-asparaginase (L-Asp) aims to improve treatment outcomes for adult patients with non-Philadelphia chromosome (Ph) acute lymphoblastic leukemia (ALL). In this measurable residual disease 2014 (MRD2014) study, we modified our protocol to include an augmented dose of native L-Asp. Compared with former MRD2008, the total dose of L-Asp was raised from 36 000 U/m<sup>2</sup> to 232 000 U/m<sup>2</sup> in patients aged 16 to 35 and from 36 000 U/m<sup>2</sup> to 132 000 U/m<sup>2</sup> in patients aged 36 to 65 years. Adult patients with ALL were enrolled between January 2014 and December 2019 based on the following eligibility criteria: non-L3 ALL, age 16 to 65 years, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate liver and kidney functions (serum bilirubin ≤ 2.0 mg/dL; serum creatinine ≤ 2.0 mg/dL). The median follow-up time was 1128 days (range, 35-2400). A total of 81 patients with non-Ph ALL (40 males and 41 females; median age, 39 years [range, 16-64]) in whom MRD status was assessed were included. Complete remission was achieved in 72 patients (89%). The probability of 3-year event-free survival (EFS) and overall survival (OS) in these patients were 55% and 72%, respectively. The outcomes for patients aged 16 to 35 years demonstrated remarkable improvement. The 3-year EFS of MRD2008 at 45% significantly increased to 71% for MRD2014. Our study unequivocally demonstrated the beneficial effects of augmented use of L-Asp in this adolescent and young adult population. This trial was registered at UMIN Clinical Trials Registry as #UMIN000012382.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000335/pdfft?md5=bbf499ae9c9b69c23bb21aa6d69f4833&pid=1-s2.0-S2950328024000335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095183","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

T-cell lymphoblastic lymphoma compared with T-cell acute lymphoblastic leukemia: similar subtypes and different fusions T 细胞淋巴细胞淋巴瘤与 T 细胞急性淋巴细胞白血病的比较：相似的亚型和不同的融合

Blood Neoplasia Pub Date : 2024-09-01 DOI: 10.1016/j.bneo.2024.100029

引用次数: 0

Targeting SLFN11-regulated pathways restores chemotherapy sensitivity in AML 靶向 SLFN11 调控通路可恢复急性髓细胞白血病化疗敏感性

Blood Neoplasia Pub Date : 2024-08-28 DOI: 10.1016/j.bneo.2024.100037

{"title":"Targeting SLFN11-regulated pathways restores chemotherapy sensitivity in AML","authors":"","doi":"10.1016/j.bneo.2024.100037","DOIUrl":"10.1016/j.bneo.2024.100037","url":null,"abstract":"<div><h3>Abstract</h3><div>Chemoresistance represents an ongoing challenge in treating patients with acute myeloid leukemia (AML), and a better understanding of the resistance mechanisms can lead to the development of novel AML therapies. Here, we demonstrated that low expression of the DNA damage response gene Schlafen 11 (<em>SLFN11</em>) correlates with poor overall survival and worse prognosis in patients with AML. Moreover, we showed that SLFN11 plays an essential role in regulating chemotherapy sensitivity in AML. AML cells with suppressed levels of SLFN11 do not undergo apoptosis in response to cytarabine because of aberrant activation of the Ataxia telangiectasia and Rad3-related protein (ATR)/Checkpoint kinase 1 (Chk1) pathway, allowing for DNA damage repair, whereas sensitivity to cytarabine can be restored by inhibiting the ATR pathway. Importantly, <em>SLFN11</em> knockout AML cells retain sensitivity to hypomethylating agents and the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Altogether, these results reveal <em>SLFN11</em> as an important regulator and predictor of chemotherapy sensitivity in AML and suggest that targeting pathways suppressed by SLFN11 may offer potential combination therapies to enhance and optimize chemotherapy responses in AML.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573254","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

Clinical and pathological features of pediatric peripheral T-cell lymphoma after solid organ transplantation 实体器官移植后小儿外周T细胞淋巴瘤的临床和病理特征

Blood Neoplasia Pub Date : 2024-08-28 DOI: 10.1016/j.bneo.2024.100039

引用次数: 0

Intensive chemotherapy after hypomethylating agent and venetoclax in adult acute myeloid leukemia 成人急性髓性白血病患者使用低甲基化药物和 Venetoclax 后的强化化疗

Blood Neoplasia Pub Date : 2024-08-28 DOI: 10.1016/j.bneo.2024.100038

{"title":"Intensive chemotherapy after hypomethylating agent and venetoclax in adult acute myeloid leukemia","authors":"","doi":"10.1016/j.bneo.2024.100038","DOIUrl":"10.1016/j.bneo.2024.100038","url":null,"abstract":"<div><h3>Abstract</h3><div>The combination of a hypomethylating agent (HMA) and venetoclax (VEN) is approved for adults aged >75 years with newly diagnosed acute myeloid leukemia (AML) as well as those ineligible for intensive chemotherapy (IC). HMA/VEN is increasingly substituted for IC in adults with AML aged <75 years, particularly in those with adverse cytogenetic and molecular features. When patients fail to respond or relapse after HMA/VEN, the utility of salvage IC is largely unknown. We performed a retrospective single-institution study and identified 46 patients who received IC after HMA/VEN, including 24 patients who received HMA/VEN as their first treatment for AML. This population had complete remission (CR)/CR with incomplete count recovery (CRi)/morphologic leukemia-free state rate of 37%, CR/CRi rate of 28%, and a median overall survival (mOS) of 7.2 months (95% confidence interval, 5.0-10.3). Patients who relapsed after an initial response to HMA/VEN and subsequently received IC were more likely to achieve a CR/CRi than those refractory to HMA/VEN (50% vs 19%; <em>P</em> = .04), although there was no statistically significant difference in survival (mOS, 8.8 vs 5.4 months; <em>P</em> = .64). Age >65 years predicted poorer survival (mOS, 4.3 vs 10.6 months; <em>P</em> < .001). IC after HMA/VEN should be further studied and chosen with caution.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442795","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

A phase 1 study adding pitavastatin to venetoclax therapy in AML and CLL/SLL: a mechanism-based drug repurposing strategy 在AML和CLL/SLL治疗中加入匹伐他汀的1期研究：基于机制的药物再利用策略

Blood Neoplasia Pub Date : 2024-08-28 DOI: 10.1016/j.bneo.2024.100036

引用次数: 0

COVID-19 vaccination in patients with classic and variant hairy cell leukemia 为典型和变异毛细胞白血病患者接种 COVID-19 疫苗

Blood Neoplasia Pub Date : 2024-08-28 DOI: 10.1016/j.bneo.2024.100035

{"title":"COVID-19 vaccination in patients with classic and variant hairy cell leukemia","authors":"","doi":"10.1016/j.bneo.2024.100035","DOIUrl":"10.1016/j.bneo.2024.100035","url":null,"abstract":"<div><h3>Abstract</h3><div>Patients with the B-cell malignancy hairy cell leukemia (HCL) and the poorer-prognosis variant HCLv often receive anti-CD20 monoclonal antibodies (mAbs), which kill normal B cells, impairing humoral immunity. We measured COVID-19 antibodies after doses of COVID-19 vaccine in patients with HCL (n = 415) and HCLv (n = 32). After the second COVID-19 vaccine dose, spike antibody level most strongly correlated with normal B-cell levels (r = 0.365, <em>P</em> < .0001), followed by CD4<sup>+</sup> T-cell count (r = 0.244, <em>P</em> = .0002), and was less related to immunoglobulin G level (r = 0.101, <em>P</em> = .14). Spike antibody also correlated with normal B cells after the third to fifth vaccine doses and with CD4<sup>+</sup> count after the third dose. Normal B-cells were undetectable in 87% of patients within 6 months after the last dose of anti-CD20 mAb and were lower than in patients at 6 to 12 months (<em>P</em> = .0003), which, in turn, were lower than at 12 to 18 months (<em>P</em> = .0002). Infection with COVID-19 became more common after use of the third vaccine dose; spike antibody levels were higher in patients with prior infection (positive vs negative nucleocapsid antibodies; <em>P</em> < .0001). Spike antibodies decreased faster after ibrutinib or anti-CD20 mAb. We conclude that decreased levels of normal B cells in patients with HCL/HCLv, due to disease and/or anti-CD20 therapy, are associated with lower COVID-19 vaccination efficiency and such patients may not respond well to vaccines. The associated studies were registered at <span><span>www.ClinicalTrials.gov</span><svg><path></path></svg></span> as #NCT01087333 (HCL/HCLv) and #NCT04362865 (COVID-19).</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442797","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