Blood最新文献_第2页

An Updated Understanding of Follicular Lymphoma Transformation. 对滤泡性淋巴瘤转化的最新认识。

IF 20.3 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2024026016

Erin M Parry,Jessica Okosun

{"title":"An Updated Understanding of Follicular Lymphoma Transformation.","authors":"Erin M Parry,Jessica Okosun","doi":"10.1182/blood.2024026016","DOIUrl":"https://doi.org/10.1182/blood.2024026016","url":null,"abstract":"While the majority of patients with follicular lymphoma (FL) follow an indolent disease course, some patients experience a critical inflection point when FL transforms into an aggressive lymphoma. Historically, FL transformation (tFL) is marked by poor outcomes, particularly for patients with prior FL-directed treatment. Compared to FL, tFL is marked by numerous additional genetic changes, upregulates novel signaling pathways and arises from an ancestral FL clone with shared FL-initiating mutations. Prediction of tFL risk remains a high-priority area of disease research, with recent work highlighting memory-like B cell phenotypes associated with transformation risk and implicating critical tumor-immune interactions at transformation emergence. Mechanistic studies provide insight into the role of genetic drivers in determining malignant B cell phenotypes or reducing microenvironmental dependencies. In parallel, a shifting therapeutic landscape marked by novel immune-based therapeutics is improving outcomes for patients, yet further clinical outcome data in tFL are greatly needed. This review summarizes recent scientific and clinical studies in tFL and provides an updated understanding of the biological basis, diagnosis and clinical management of tFL. We conclude with a proposed plan of future research aimed at the goal of increasing tFL biologic knowledge and improving outcomes for patients with tFL.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"42 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prevention is better than cure. 预防胜于治疗。

IF 21 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2025029023

Olaf Penack

引用次数: 0

How I Evaluate and Treat Resistance and Relapse in CML. 我如何评估和治疗CML的耐药和复发。

IF 20.3 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2024026511

Simona Soverini,Fausto Castagnetti

{"title":"How I Evaluate and Treat Resistance and Relapse in CML.","authors":"Simona Soverini,Fausto Castagnetti","doi":"10.1182/blood.2024026511","DOIUrl":"https://doi.org/10.1182/blood.2024026511","url":null,"abstract":"As evidenced by the excellent survival outcomes, chronic myeloid leukemia (CML) treatment in the era of tyrosine kinase inhibitors (TKIs) is often successful. However, when response milestones are not met or lost, treatment decision-making may be challenging. The availability for first-, second- or subsequent-line use of six different TKIs, each with definite and often non-overlapping features in terms of mechanism of action, potency, activity against resistance mutations and tolerability profile provides a reassuring opportunity to rescue an optimal response, but it must be exploited carefully to avoid hasty or inappropriate choices. When and how to sequence TKIs, and if and when to consider transplant are very important issues. 'One for all' rules cannot be formulated, since for each individual patient the decision process requires investigation and integration of a series of clinical and biological factors. After discussing how resistance is defined, we here aim to provide practical guidance to therapeutic reassessment, discussing which laboratory investigations should be performed, how they should be interpreted, which additional clinical considerations are mandatory, and how these factors should be weighed and reasonably concur to the final decision.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"14 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How I treat patients who are refractory to platelet transfusions. 我如何治疗对血小板输注难治的病人。

IF 21 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2023022883

Susan Nahirniak, Veera Nadarajan, Simon J Stanworth

引用次数: 0

How I treat challenging transfusion cases in sickle cell disease. 我如何治疗镰状细胞病中的疑难输血病例？

IF 21 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2023023648

Stella T Chou, Jeanne E Hendrickson

{"title":"How I treat challenging transfusion cases in sickle cell disease.","authors":"Stella T Chou, Jeanne E Hendrickson","doi":"10.1182/blood.2023023648","DOIUrl":"10.1182/blood.2023023648","url":null,"abstract":"Abstract: Transfusion of red blood cells (RBCs) can be lifesaving for individuals living with sickle cell disease (SCD). However, alloimmunization after transfusion is more common with patients with SCD than in other patient populations, resulting in morbidity and mortality. Management of complications related to RBC alloantibodies, including delayed hemolytic transfusion reactions (DHTRs) and identifying compatible RBCs for future transfusions, remains a challenge for hematologists and transfusion medicine providers. Although transfusion guidelines from organizations, including the American Society for Hematology provide general recommendations, individual cases remain challenging. Antibody evanescence and the lack of widespread RBC alloantibody data sharing across hospitals pose unique challenges, as do RH variants in both transfusion recipients and blood donors. Further, as potentially curative therapies require RBC transfusions to lower the hemoglobin S before cellular therapy collections and infusions, patients who are highly alloimmunized may be deemed ineligible. The cases described are representative of clinical dilemmas the authors have encountered, and the approaches are as evidence-based as the literature and the authors' experiences allow. A future desired state is one in which RBC alloantibody data are efficiently shared across institutions, Rh alloimmunization can be mitigated, better treatments exist for DHTRs, and a label of difficult to transfuse does not prevent desired therapies.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2257-2265"},"PeriodicalIF":21.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IAP dependency of T-cell prolymphocytic leukemia identified by high-throughput drug screening. 高通量药物筛选鉴定t细胞前淋巴细胞白血病IAP依赖性

IF 21 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2024027171

Marcel Fabian Pohly, Kerstin Putzker, Sebastian Scheinost, Lena Ben Taarit, Tatjana Walther, Sandra Kummer, Tobias Wertheimer, Minqi Lin, Thi Huong Lan Do, Kristina Handler, Jan Michler, Jarno Kivioja, Karsten Bach, Samanta Kisele, James Kim, Sascha Dietrich, Beat Bornhauser, Wendy Wei-Lynn Wong, Burkhard Becher, Andreas Moor, Joe Lewis, Xenia Ficht, Junyan Lu, Wolfgang Huber, Thorsten Zenz

{"title":"IAP dependency of T-cell prolymphocytic leukemia identified by high-throughput drug screening.","authors":"Marcel Fabian Pohly, Kerstin Putzker, Sebastian Scheinost, Lena Ben Taarit, Tatjana Walther, Sandra Kummer, Tobias Wertheimer, Minqi Lin, Thi Huong Lan Do, Kristina Handler, Jan Michler, Jarno Kivioja, Karsten Bach, Samanta Kisele, James Kim, Sascha Dietrich, Beat Bornhauser, Wendy Wei-Lynn Wong, Burkhard Becher, Andreas Moor, Joe Lewis, Xenia Ficht, Junyan Lu, Wolfgang Huber, Thorsten Zenz","doi":"10.1182/blood.2024027171","DOIUrl":"10.1182/blood.2024027171","url":null,"abstract":"Abstract: T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoid malignancy with limited treatment options. To discover new treatment targets for T-PLL, we performed high-throughput drug sensitivity screening on 30 primary patient samples ex vivo. After screening >2800 unique compounds, we found T-PLL to be more resistant to most drug classes, including chemotherapeutics, than other blood cancers. Furthermore, we discovered previously unreported vulnerabilities of T-PLL. T-PLL cells exhibited a particular sensitivity to drugs targeting autophagy (thapsigargin and bafilomycin A1), nuclear export (selinexor), and inhibitor of apoptosis proteins (IAPs; birinapant), sensitivities that were also shared by other T-cell malignancies. Through bulk and single-cell RNA sequencing, we found these compounds to activate the Toll-like receptor (bafilomycin A1), p53 (selinexor), and tumor necrosis factor α (TNF-α)/NF-κB signaling pathways (birinapant) in T-PLL cells. Focusing on birinapant for its potential in drug repurposing, we uncovered that IAP inhibitor-induced cell death was primarily necroptotic and dependent on TNF-α. Through spectral flow cytometry, we confirmed the absence of cleaved caspase-3 in IAP inhibitor-treated T-PLL cells and show that IAP inhibition reduces the proliferation of T-PLL cells stimulated ex vivo, while showing only a limited effect on nonmalignant T-cells. In summary, our study maps the drug sensitivity of T-PLL across a broad range of targets and identifies new therapeutic approaches for T-PLL by targeting IAPs, exportin 1, and autophagy, highlighting potential candidates for drug repurposing and novel treatment strategies.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2336-2352"},"PeriodicalIF":21.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study. 高危大b细胞淋巴瘤（ZUMA-12）一线治疗的3年随访分析

IF 21 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2024027347

Julio C Chavez, Michael Dickinson, Javier Munoz, Matthew L Ulrickson, Catherine Thieblemont, Olalekan O Oluwole, Alex F Herrera, Chaitra S Ujjani, Yi Lin, Peter A Riedell, Natasha Kekre, Sven de Vos, Jacob Wulff, Chad M Williams, Joshua Winters, Ioana Kloos, Hairong Xu, Sattva S Neelapu

{"title":"Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study.","authors":"Julio C Chavez, Michael Dickinson, Javier Munoz, Matthew L Ulrickson, Catherine Thieblemont, Olalekan O Oluwole, Alex F Herrera, Chaitra S Ujjani, Yi Lin, Peter A Riedell, Natasha Kekre, Sven de Vos, Jacob Wulff, Chad M Williams, Joshua Winters, Ioana Kloos, Hairong Xu, Sattva S Neelapu","doi":"10.1182/blood.2024027347","DOIUrl":"10.1182/blood.2024027347","url":null,"abstract":"ZUMA-12 is a multicenter phase 2 study evaluating axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy as part of first-line treatment for high-risk large B-cell lymphoma (LBCL). In the primary efficacy analysis (n = 37; median follow-up, 15.9 months), axi-cel demonstrated a high rate of complete responses (CR; 78%) and a safety profile consistent with prior experience. Here, we assessed updated outcomes from ZUMA-12 in 40 treated patients after ≥3 years of follow-up. Eligible adults underwent leukapheresis, lymphodepleting chemotherapy, and axi-cel infusion (2 × 106 CAR T cells/kg). Investigator-assessed CR, objective response, survival, safety, and CAR T-cell expansion were assessed. The CR rate among response-evaluable patients (n = 37) increased after the primary analysis to 86% (95% confidence interval [CI], 71%-95%), with a 92% objective response rate. After a median follow-up of 47.0 months (range, 37.1-57.8 months), 36-month estimates (95% CI) of duration of response and event-free, progression-free, and overall survival were 81.8% (63.9%-91.4%), 73.0% (55.6%-84.4%), 75.1% (57.5%-86.2%), and 81.1% (64.4%-90.5%), respectively. In total, 4 patients had new malignancies, 2 occurring after the data cutoff of the primary analysis; none were axi-cel-related. Eight patients died on study, 2 of whom died from nonrelapse mortality causes. After long-term follow-up, axi-cel demonstrated a high durable response rate, with no new safety signals after the primary analysis, suggestive of an effective first-line therapy with curative intent in high-risk LBCL. Further assessments are needed to determine its benefit vs standard of care. This trial was registered at clinicaltrials.gov, as NCT03761056.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2303-2311"},"PeriodicalIF":21.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low rates of chronic graft-versus-host disease with ruxolitinib maintenance following allogeneic HCT. 同种异体HCT后慢性移植物抗宿主病发生率低，鲁索替尼维持。

IF 21 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2024028005

Zachariah DeFilipp, Haesook T Kim, Laura W Knight, Suzanne M O'Connor, Shilton E Dhaver, Meghan White, Bhagirathbhai Dholaria, Mark A Schroeder, Sumithira Vasu, Sameem Abedin, Jooho Chung, Areej El-Jawahri, Matthew J Frigault, Steven McAfee, Richard A Newcomb, Paul V O'Donnell, Thomas R Spitzer, Yi-Bin Chen, Gabriela S Hobbs

{"title":"Low rates of chronic graft-versus-host disease with ruxolitinib maintenance following allogeneic HCT.","authors":"Zachariah DeFilipp, Haesook T Kim, Laura W Knight, Suzanne M O'Connor, Shilton E Dhaver, Meghan White, Bhagirathbhai Dholaria, Mark A Schroeder, Sumithira Vasu, Sameem Abedin, Jooho Chung, Areej El-Jawahri, Matthew J Frigault, Steven McAfee, Richard A Newcomb, Paul V O'Donnell, Thomas R Spitzer, Yi-Bin Chen, Gabriela S Hobbs","doi":"10.1182/blood.2024028005","DOIUrl":"10.1182/blood.2024028005","url":null,"abstract":"Abstract: Despite recent advances in graft-versus-host disease (GVHD) prophylaxis, novel approaches to effective prevention of chronic GVHD (cGVHD) remain of high importance. In this prospective, multicenter, phase 2 trial, ruxolitinib, an oral inhibitor of Janus kinase (JAK) 1 and 2, was administered as maintenance therapy after reduced-intensity allogeneic hematopoietic cell transplantation (HCT). GVHD prophylaxis consisted of tacrolimus and methotrexate. Ruxolitinib began between day +30 to 100 and was administered continuously in 28-day cycles for up to 24 cycles. Seventy-eight participants were enrolled before HCT; 63 participants received the intervention. The median start date of ruxolitinib after HCT was day +45. The most common grade ≥3 adverse events were neutropenia, thrombocytopenia, and anemia. Seven participants experienced grade ≥3 infectious events. GVHD-free, relapse-free survival at 1 year after HCT, the primary end point, was 70%. Grade 3 to 4 acute GVHD at 6 months was 4.8%, and moderate-severe cGVHD at 2 years was 16%. cGVHD requiring systemic therapy was 9.5% at 1 year and 13% at 2 years. Overall survival and progression-free survival at 2 years were 76% and 68%, respectively. Prolonged administration of ruxolitinib following HCT is associated with low rates of clinically significant cGVHD. The incorporation of JAK inhibition into GVHD prevention approaches warrants further investigation. This trial was registered at www.clinicaltrials.gov as #NCT03286530.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2312-2316"},"PeriodicalIF":21.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CARs in pole position: ready for the race? 处于杆位的赛车：准备好比赛了吗？

IF 20.3 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2025028354

Guillaume Manson,Roch Houot

引用次数: 0

Expanding the universe of T-PLL targets. 扩展T-PLL目标的范围。

IF 20.3 1区医学

Blood Pub Date : 2025-05-15 DOI: 10.1182/blood.2025028353

Marwan Kwok,Tatjana Stankovic

引用次数: 0