American Journal of Hematology最新文献

{"title":"Moderate–severe beta-thalassemia intermedia phenotype caused by sextuplicated alpha-globin gene allele in two beta-thalassemia carriers","authors":"Ahlem Achour,&nbsp;Jeroen Knijnenburg,&nbsp;Tamara Koopmann,&nbsp;Amir Raz,&nbsp;Marc Tischkowitz,&nbsp;Thomas D. Coates,&nbsp;F. Baas,&nbsp;C. L. Harteveld","doi":"10.1002/ajh.27386","DOIUrl":"10.1002/ajh.27386","url":null,"abstract":"<p>Beta-thalassemia intermedia is caused by homo- or compound heterozygosity for beta-thalassemia variants reducing the beta-globin synthesis and encompasses a wide clinical spectrum ranging from non-transfusion dependent hemolytic anemia to occasional blood transfusion dependency. Carriers of beta-thalassemia are usually clinically asymptomatic. Only rarely beta-thalassemia carriers express symptoms of beta-thalassemia intermedia such as splenomegaly, growth retardation, and moderate to severe anemia.</p><p>In adults, HbA is composed of two alpha-globin and two beta-globin chains, which are coded for by the duplicated alpha-globin genes (<i>HBA2</i> and <i>HBA1</i>) on chromosome 16 and single beta-globin gene (<i>HBB</i>) on chromosome 11. The Major Conserved Sequences 1 to 4 (MCS1-4) regulates the expression of the alpha-genes, while the beta-Locus Control Region does the same for the beta-genes. The alpha/beta protein synthesis is balanced to a ratio of 1. Genetic defects in the globin genes may lead to a reduced or absent synthesis of alpha- or beta-globin causing alpha- or beta-thalassemia respectively. The excess of unbound alpha-globin chain forms nonfunctional unsolvable tetramers damaging the red cell membrane and is held responsible for the observed ineffective erythropoiesis in beta-thalassemia Intermedia and Major patients.<span>¹</span> Several molecular mechanisms are held responsible of causing a beta-thalassemia intermedia phenotype in carriers. Co-inheritance of extra copies of the alpha-globin genes, causing an increasing unbalanced alpha-/beta-globin synthesis ratio is one of these mechanism.<span>²</span> Here we report the first alpha-cluster segmental triplication in four individuals of the same family leading to a total of eight alpha-genes. The two probands are also carrier of a known beta++-thalassemia variant (β + AATAAG ClinVar Id:15473) resulting in a moderate beta-thalassemia intermedia phenotype.</p><p>The family was referred for investigation for the first time in 2008 (father I-1, mother I-2, eldest son II-1 and proband II-2) because of a suspected beta-thalassemia trait with unexplained more severe clinical expression in proband II-2. In 2022, the family was reinvestigated after the birth of two other children, II-3 and II-4, the last showing a pronounced microcytic hypochromic anemia similar to his sister (proband II-2) (Figure 1a in Supplementary online data).</p><p>Proband II-2 was diagnosed with hypochromic microcytic anemia at 1 year of age (MCH 18.5 pg, MCV 56.8 fL, Hb 88 g/L) with mildly elevated HbA2 (3.4%) and normal ferritin (28 μg/L). She was found to be carrier of a beta+-thalassemia variant (<i>NM_000518.5(HBB):c.*113A&gt;G</i>) inherited from her father, which however did not explain her red cell hematology. When the family was analyzed in 2022, her hematologic parameters were still low (MCH 17.9 pg, MCV 60.8 fL, Hb 90 g/L) and she had developed hepatosplenomegaly. Transfusion ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic value of blood cellular indices in pulmonary embolism","authors":"Fakiha Siddiqui,&nbsp;Alfonso Tafur,&nbsp;Mushtaq Hussain,&nbsp;Alberto García-Ortega,&nbsp;Amir Darki,&nbsp;Jawed Fareed,&nbsp;David Jiménez,&nbsp;Behnood Bikdeli,&nbsp;Francisco Galeano-Valle,&nbsp;José Luis Fernández-Reyes,&nbsp;Montserrat Pérez-Pinar,&nbsp;Manuel Monreal,&nbsp;the RIETE Investigators","doi":"10.1002/ajh.27379","DOIUrl":"10.1002/ajh.27379","url":null,"abstract":"<p>Prognostication in acute pulmonary embolism (PE) requires reliable markers. While cellular indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) appear promising, their utility in PE prognostication needs further exploration. We utilized data from the RIETE registry and the Loyola University Medical Center (LUMC) to assess the prognostic value of NLR, PLR, and SII in acute PE, using logistic regression models. The primary outcome was 30-day all-cause mortality. We compared their prognostic value versus the simplified Pulmonary Embolism Severity Index (sPESI) alone. We included 10 085 patients from RIETE and 700 from the LUMC. Thirty-day mortality rates were 4.6% and 8.3%, respectively. On multivariable analysis, an elevated NLR (&gt;7.0) was associated with increased mortality (adjusted odds ratio [aOR]: 3.46; 95% CI: 2.60–4.60), outperforming the PLR &gt; 220 (aOR: 2.36; 95% CI: 1.77–3.13), and SII &gt; 1600 (aOR: 2.52; 95% CI: 1.90–3.33). The c-statistic for NLR in patients with low-risk PE was 0.78 (95% CI: 0.69–0.86). Respective numbers were 0.66 (95% CI: 0.63–0.69) and 0.68 (95% CI: 0.59–0.76) for intermediate-risk and high-risk patients. These findings were mirrored in the LUMC cohort. Among 9810 normotensive patients in RIETE, those scoring 0 points in sPESI and with an NLR ≤ 7.0 (35% of the population) displayed superior sensitivity (97.1%; 95% CI: 95.5–98.7) and negative predictive value (99.7%; 95% CI: 99.5–99.8) than sPESI alone (87.1%; 95% CI: 83.9–90.3, and 98.7%; 95% CI: 98.4–99.1, respectively) for 30-day mortality. The NLR is a significant prognostic marker for 30-day mortality in PE patients, especially useful to identify patients with very low-risk PE.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178892","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}

{"title":"Toxicities associated with tyrosine kinase inhibitor maintenance following allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia","authors":"Tamer Othman,&nbsp;Paul Koller,&nbsp;Ni-Chun Tsai,&nbsp;Dongyun Yang,&nbsp;Hoda Pourhassan,&nbsp;Vaibhav Agrawal,&nbsp;Dat Ngo,&nbsp;Jason Chen,&nbsp;Leonardo Farol,&nbsp;Ricardo Spielberger,&nbsp;Firoozeh Sahebi,&nbsp;Monzr M. Al Malki,&nbsp;Ji-Lian Cai,&nbsp;Karamjeet S. Sandhu,&nbsp;Joshua Mansour,&nbsp;Amandeep Salhotra,&nbsp;Haris Ali,&nbsp;Ahmed Aribi,&nbsp;Shukaib Arslan,&nbsp;Guido Marcucci,&nbsp;Stephen J. Forman,&nbsp;Anthony S. Stein,&nbsp;Ryotaro Nakamura,&nbsp;Vinod Pullarkat,&nbsp;Ibrahim Aldoss,&nbsp;Matthew Mei","doi":"10.1002/ajh.27378","DOIUrl":"10.1002/ajh.27378","url":null,"abstract":"<p>Allogeneic hematopoietic cell transplantation (HCT) offers a potential cure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); nonetheless, relapses are common and the major cause of mortality. One strategy to prevent relapse is tyrosine kinase inhibitor (TKI) maintenance post-HCT, but published clinical experience is primarily with the first-generation TKI imatinib while data with newer generation TKIs are limited. We conducted a retrospective analysis of 185 Ph+ ALL patients who underwent HCT followed by TKI maintenance from 2003 to 2021 at City of Hope. Initially, 50 (27.0%) received imatinib, 118 (63.8%) received a second-generation TKI (2G-TKI), and 17 (9.2%) received ponatinib. A total of 77 patients (41.6%) required a dose reduction of their initial TKI due to toxicity. Sixty-six patients (35.7%) did not complete maintenance due to toxicity; 69 patients (37.3%) discontinued 1 TKI, and 11 (5.9%) discontinued 2 TKIs due to toxicity. Initial imatinib versus 2G-TKI versus ponatinib maintenance was discontinued in 19 (38.0%) versus 68 (57.6%) versus 3 (17.6%) patients due to toxicity (<i>p</i> = .003), respectively. Patients on ponatinib as their initial TKI had a longer duration of TKI maintenance versus 2G-TKI: 576.0 days (range, 72–921) versus 254.5 days (range, 3–2740; <i>p</i> = .02). The most common reasons for initial TKI discontinuation include gastrointestinal (GI) intolerance (15.1%), cytopenia (8.6%), and fluid retention (3.8%). The 5-year overall survival and progression-free survival for the total population were 78% and 71%, respectively. Our findings demonstrate the challenges of delivering post-HCT TKI maintenance in a large real-world cohort as toxicities leading to TKI interruptions, discontinuation, and dose reduction were common.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157797","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}

{"title":"Outcomes following allogeneic hematopoietic cell transplantation relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia","authors":"Tamer Othman,&nbsp;Shanpeng Li,&nbsp;Jianying Zhang,&nbsp;Hoda Pourhassan,&nbsp;Vaibhav Agrawal,&nbsp;Dat Ngo,&nbsp;Jason Chen,&nbsp;Leonardo Farol,&nbsp;Firoozeh Sahebi,&nbsp;Karamjeet Sandhu,&nbsp;Ricardo Spielberger,&nbsp;Guido Marcucci,&nbsp;Stephen J. Forman,&nbsp;Anthony S. Stein,&nbsp;Ryotaro Nakamura,&nbsp;Vinod Pullarkat,&nbsp;Matthew Mei,&nbsp;Ibrahim Aldoss,&nbsp;Paul Koller","doi":"10.1002/ajh.27365","DOIUrl":"10.1002/ajh.27365","url":null,"abstract":"<p>Improved first progression-free survival following allogeneic hematopoietic cell transplantation relapse with the use of immunotherapy.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SUGP2 p.(Arg639Gln) variant is involved in the pathogenesis of hemochromatosis via the CIRBP/BMPER signaling pathway","authors":"Yanmeng Li,&nbsp;Anjian Xu,&nbsp;Susu Liu,&nbsp;Wei Zhang,&nbsp;Donghu Zhou,&nbsp;Qin OuYang,&nbsp;Huaduan Zi,&nbsp;Bei Zhang,&nbsp;Ning Zhang,&nbsp;Wei Geng,&nbsp;Yiming Zhou,&nbsp;Weijia Duan,&nbsp;Xiaoming Wang,&nbsp;Xinyan Zhao,&nbsp;Xiaojuan Ou,&nbsp;Changfa Fan,&nbsp;Jidong Jia,&nbsp;Jian Huang","doi":"10.1002/ajh.27377","DOIUrl":"10.1002/ajh.27377","url":null,"abstract":"<p>Pathogenic variants in <i>HFE</i> and non-<i>HFE</i> genes have been identified in hemochromatosis in different patient populations, but there are still a certain number of patients with unexplained primary iron overload. We recently identified in Chinese patients a recurrent p.(Arg639Gln) variant in SURP and G-patch domain containing 2 (SUGP2), a potential mRNA splicing-related factor. However, the target gene of SUGP2 and affected iron-regulating pathway remains unknown. We aimed to investigate the pathogenicity and underlying mechanism of this variant in hemochromatosis. RNA-seq analysis revealed that SUGP2 knockdown caused abnormal alternative splicing of <i>CIRBP</i> pre-mRNA, resulting in an increased normal splicing form of <i>CIRBP</i> V1, which in turn increased the expression of <i>BMPER</i> by enhancing its mRNA stability and translation. Furthermore, RNA-protein pull-down and RNA immunoprecipitation assays revealed that SUGP2 inhibited splicing of <i>CIRBP</i> pre-mRNA by a splice site variant at <i>CIRBP</i> c.492 and was more susceptible to <i>CIRBP</i> c.492 C/C genotype. Cells transfected with SUGP2 p.(Arg639Gln) vector showed up-regulation of <i>CIRBP</i> V1 and BMPER expression and down-regulation of pSMAD1/5 and <i>HAMP</i> expression. CRISPR-Cas9 mediated SUGP2 p.(Arg622Gln) knock-in mice showed increased iron accumulation in the liver, higher total serum iron, and decreased serum hepcidin level. A total of 10 of 54 patients with hemochromatosis (18.5%) harbored the <i>SUGP2</i> p.(Arg639Gln) variant and carried <i>CIRBP</i> c.492 C/C genotype, and had increased BMPER expression in the liver. Altogether, the <i>SUGP2</i> p.(Arg639Gln) variant down-regulates hepcidin expression through the SUGP2/CIRBP/BMPER axis, which may represent a novel pathogenic factor for hemochromatosis.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral blood stem cell versus bone marrow graft for patients ≥60 years undergoing reduced intensity conditioning haploidentical transplantation for acute myeloid leukemia in complete remission: An analysis of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation","authors":"Raynier Devillier,&nbsp;Jacques-Emmanuel Galimard,&nbsp;Didier Blaise,&nbsp;Anna Maria Raiola,&nbsp;Stefania Bramanti,&nbsp;Giovanni Grillo,&nbsp;Rocco Pastano,&nbsp;Régis Peffault de Latour,&nbsp;Alessandro Busca,&nbsp;Lucía López-Corral,&nbsp;Arancha Bermúdez Rodríguez,&nbsp;Christoph Schmid,&nbsp;Edouard Forcade,&nbsp;Jan Vydra,&nbsp;Carlos Solano,&nbsp;Gesine Bug,&nbsp;Andreas Neubauer,&nbsp;Amandine Charbonnier,&nbsp;Eolia Brissot,&nbsp;Arnon Nagler,&nbsp;Fabio Ciceri,&nbsp;Mohamad Mohty","doi":"10.1002/ajh.27343","DOIUrl":"10.1002/ajh.27343","url":null,"abstract":"<p>In the context of T-cell replete haploidentical stem cell transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy), it is still unknown whether peripheral blood (PB) or bone marrow (BM) is the best graft source. While PB is associated with a higher incidence of graft-versus-host disease (GVHD), it may induce a stronger graft-versus-leukemia effect compared to BM, notably in acute myeloid leukemia (AML). From the EBMT registry database, we compared T-cell replete PB (<i>n</i> = 595) versus BM (<i>n</i> = 209) grafts in a large cohort of 804 patients over the age of 60 years who underwent Haplo-SCT with PT-Cy for an AML in first or second complete remission. The risk of acute GVHD was significantly higher in the PB group (Grade II-IV: HR = 1.67, 95% CI [1.10–2.54], <i>p</i> = 0.01; Grade III-IV: HR = 2.29, 95% CI [1.16–4.54], <i>p</i> = 0.02). No significant difference was observed in chronic GVHD or non-relapse mortality. In the PB group, the risk of relapse was significantly lower in the PB group (HR = 0.65, 95% CI [0.45–0.94], <i>p</i> = 0.02) and leukemia-free survival was significantly better (HR = 0.76, 95% CI [0.59–0.99], <i>p</i> = 0.04), with a trend toward better overall survival (HR = 0.78, 95% CI [0.60–1.01], <i>p</i> = 0.06). We conclude that in the specific context of Haplo-SCT with PT-Cy, PB grafts represent a valid option to decrease the risk of relapse and improve outcome of older AML patients who usually do not benefit from conditioning intensification.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080396","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}

{"title":"Comparative histological analysis of spleens in pediatric patients with hemolytic anemias: Insights into the pathophysiological mechanisms of spleen destruction in sickle cell anemia","authors":"Valentine Brousse,&nbsp;Sara El Hoss,&nbsp;Pierre Isnard,&nbsp;Sandrine Laurance,&nbsp;Camille Lambert,&nbsp;Liza Ali,&nbsp;Arnaud Bonnard,&nbsp;Carmen Capito,&nbsp;Sabine Sarnacki,&nbsp;D. Berrebi,&nbsp;Berengère Koehl,&nbsp;Malika Benkerrou,&nbsp;Florence Missud,&nbsp;Laurent Holvoet,&nbsp;Ghislaine Ithier,&nbsp;Mariane de Montalembert,&nbsp;Slimane Allali,&nbsp;Leon Tshilolo,&nbsp;Jacques Diebold,&nbsp;Thierry Jo Molina","doi":"10.1002/ajh.27374","DOIUrl":"10.1002/ajh.27374","url":null,"abstract":"<p>While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to increased red blood cell (RBC) turnover, SCA is specifically characterized by susceptibility to infections. In this study, histological lesions in the spleens of pediatric patients with SCA were analyzed, in close correlation with past clinical history and comparatively to HS, healthy and transfused β-thalassemia patients (TDT). An evaluation of red pulp elementary lesions (red pulp fibrosis, iron deposition, number of Gandy–Gamna, and RBC trapping) combined into a severity score was established, as well as B-cell follicles analysis. Quantification on digitalized slides of iron deposition, RBC trapping, and red pulp fibrosis was additionally performed. Spleens from 22 children with SCA, eight with HS, eight with TDT, and three healthy controls (HC) were analyzed. Median age at splenectomy was not different between SCA and HS patients, 6.05 years (range: 4.5–16.0) versus 4.75 (range: 2.2–9.5). Marked heterogeneity was found in SCA spleens in contrast to other conditions<i>.</i> Contrary to previous reports, B-cell follicles were generally preserved in SCA. While RBC trapping was significantly increased in both SCA and HS (compared to TDT and HC), quantitative fibrosis and overall red pulp severity score were significantly increased in SCA spleens compared to other conditions. Moreover, there was an inverse correlation between quantitative fibrosis and number of B-cell follicles, linking these two compartments as well as spleen fibrosis to infectious susceptibility in SCA, potentially through impaired red pulp macrophage scavenging and B-cell subpopulations defects.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric antigen receptor T-cell therapy in secondary central nervous system lymphoma: A multicenter analysis","authors":"Aseel Alsouqi,&nbsp;Gulrayz Ahmed,&nbsp;Juntian Wang,&nbsp;Giulio Cassanello,&nbsp;Aniko Szabo,&nbsp;Alexandra E. Rojek,&nbsp;Peter A. Riedell,&nbsp;Farrukh Awan,&nbsp;Laura Samples,&nbsp;Mazyar Shadman,&nbsp;Marie Hu,&nbsp;Veronika Bachanova,&nbsp;William Wesson,&nbsp;Nausheen Ahmed,&nbsp;Madiha Iqbal,&nbsp;Mohamed A. Kharfan-Dabaja,&nbsp;Michael Scordo,&nbsp;P. Connor Johnson,&nbsp;Yi-Bin Chen,&nbsp;Sawa Ito,&nbsp;Mehdi Hamadani,&nbsp;Matthew Frigault","doi":"10.1002/ajh.27354","DOIUrl":"10.1002/ajh.27354","url":null,"abstract":"<p>Secondary central nervous system (CNS) involvement with aggressive B-cell lymphoma (henceforth referred to as SCNSL), either at initial diagnosis, or at the time of disease relapse is associated with poor outcomes. Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of non-Hodgkin lymphomas, however, most pivotal CAR-T trials excluded patients with SCNSL.<span>¹</span> Little is known about the efficacy of CAR-T therapy in patients with history of versus active SCNSL. We report here the clinical outcomes of CAR-T in SCNSL patients, with focus on outcomes of patients with active versus prior secondary CNS involvement.</p><p>This is a retrospective study including SCNSL patients with a diagnosis of diffuse large-B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, transformed follicular lymphoma (tFL), or Burkitt lymphoma who underwent commercial CD19-directed CAR-T therapies at 10 academic institutions in the United States. SCNSL involvement was defined as evidence of parenchymal or leptomeningeal involvement with lymphoma at any time prior to receiving CAR-T therapy. Active CNS disease was defined as the detection of lymphoma within the CNS at the last assessment performed prior to CAR-T infusion (magnetic resonance imaging and/or lumbar puncture).</p><p>Systemic and CNS responses were assessed using Lugano criteria<span>²</span> and the International Primary CNS Lymphoma Collaborative Group guidelines, respectively.<span>³</span> Cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded using the ASTCT consensus criteria.<span>⁴</span> This study was approved by the institutional review boards at each participating institution. Survival analysis was done using Kaplan–Meier survival estimates and log-rank test.</p><p>A total of 113 CAR-T recipients with active (<i>N</i> = 86), or history of (<i>N</i> = 27) SCNSL were included in this analysis (Table 1). Median age at the time of CAR-T was 62 years. DLBCL was the most common subtype (<i>N</i> = 88; 78%) followed by tFL (<i>N</i> = 13; 12%). The median number of prior therapy lines was 3 (range: 1–8). Twenty-two patients (19%) underwent transplantation prior to CAR-T therapy. Nineteen patients (17%) received CNS-directed radiation therapy while 24 patients (21%) received a Bruton's tyrosine kinase inhibitor (BTKi) within a month prior to CAR-T infusion. Tisagenlecleucel (tisa-cel) was prescribed in 46 (41%) patients, axicabtagene ciloleucel (axi-cel) in 44 (39%), and liso-cel in 23 (20%) patients. Supplemental Table 1 shows baseline characteristics by the type of CAR-T product used. The median follow-up was 10.7 months (IQR 6.5, 30.69). Among the 86 (76%) patients with active CNS disease, the site(s) of CNS involvement included: parenchymal disease (<i>N</i> = 35; 41%), leptomeningeal involvement (<i>N</i> = 33; 38%), or both (<i>N</i> = 18; 21%).</p><p>CRS developed in 85 (75%) ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment-associated decline in JAK2V617F allele burden in polycythemia vera: What does it mean?","authors":"Ayalew Tefferi,&nbsp;Animesh Pardanani,&nbsp;Naseema Gangat","doi":"10.1002/ajh.27375","DOIUrl":"10.1002/ajh.27375","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management","authors":"Andres Ramirez-Gamero,&nbsp;Humberto Martínez-Cordero,&nbsp;Brady E. Beltrán,&nbsp;Jorge Florindez,&nbsp;Luis Malpica,&nbsp;Jorge J. Castillo","doi":"10.1002/ajh.27376","DOIUrl":"10.1002/ajh.27376","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Disease Overview</h3>\u0000 \u0000 <p>Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Diagnosis</h3>\u0000 \u0000 <p>The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and <i>MYC</i> gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Risk Stratification</h3>\u0000 \u0000 <p>Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Management</h3>\u0000 \u0000 <p>Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}