Jing Luo, Jiaojiao Zhang, Ligen Liu, Rong Wei, Yonghua Yao, Min Xu, Jumei Shi, Jianmin Yang, Jian Hou, Jin Wang, Jian-Qing Mi
{"title":"Efficacy and safety of zanubrutinib monotherapy for chronic lymphocytic leukemia/small lymphocytic lymphoma: A multicenter, real-world study in China.","authors":"Jing Luo, Jiaojiao Zhang, Ligen Liu, Rong Wei, Yonghua Yao, Min Xu, Jumei Shi, Jianmin Yang, Jian Hou, Jin Wang, Jian-Qing Mi","doi":"10.1002/ajh.27519","DOIUrl":"https://doi.org/10.1002/ajh.27519","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567748","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}
Courtney D. DiNardo, Keith W. Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Árpád Illés, Inho Kim, Vladimir Ivanov, Grace Ku, Catherine L. Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher
<p>Based on results from the randomized, placebo-controlled phase 3 VIALE-A (NCT02993523) and VIALE-C (NCT03069352) trials,<span><sup>1-4</sup></span> venetoclax in combination with hypomethylating agents or low-dose cytarabine (LDAC) has become standard of care in patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Cytopenias are common adverse events with venetoclax and are primarily managed with protocol-mandated dose modifications, including dose interruptions and cycle delays.<span><sup>2, 5</sup></span> Neutropenia and febrile neutropenia may be mitigated with granulocyte-colony stimulating factor (G-CSF)<span><sup>4, 6</sup></span>; however, limited evidence exists on G-CSF use and impact on safety and efficacy in patients receiving low-intensity therapies. The present analysis assessed outcomes by G-CSF use post-remission (i.e., following blast clearance) among patients with newly diagnosed, intensive-chemotherapy–ineligible AML who received venetoclax-azacitidine or venetoclax-LDAC in the VIALE-A and VIALE-C trials, respectively.</p> <p>VIALE-A and VIALE-C study designs have been previously described.<span><sup>1, 3</sup></span> Both trials enrolled patients aged ≥18 years with newly diagnosed AML who were ineligible for induction chemotherapy (aged ≥75 years or with comorbid conditions precluding intensive chemotherapy treatment). In VIALE-A, patients received venetoclax-azacitidine or placebo-azacitidine; in VIALE-C, patients received venetoclax-LDAC or placebo-LDAC. Both trial protocols allowed G-CSF use with administration for cytopenia management as per institutional practice. In this exploratory post hoc analysis, patients treated with venetoclax combinations who had achieved a best response of complete remission (CR)/CR with incomplete hematologic recovery (CRi) were assessed for outcomes by G-CSF use, including overall survival (OS), duration of CR/CRi (DOR), and safety. G-CSF use was analyzed from the time of remission achievement (post-remission), defined as blast clearance (<5% bone marrow blasts) for this analysis. Clinical data cutoff was December 1, 2021 for VIALE-A and February 15, 2021 for VIALE-C.<span><sup>2, 3</sup></span> The analysis populations included patients who achieved best response of CR/CRi, unless otherwise specified.<span><sup>1, 3</sup></span> Data presentation is descriptive in nature, and formal statistical comparisons were not performed due to the post hoc nature of this analysis. Additional details are in the Data S1.</p> <p>Approximately half of patients treated with venetoclax combinations in VIALE-A and VIALE-C received G-CSF post-remission. In VIALE-A, 50% (95/191) of CR/CRi responders in the venetoclax-azacitidine arm and 26% (11/42) in the placebo-azacitidine arm received G-CSF post-remission (Tables S1 and S2). In VIALE-C, 46% (32/69) of CR/CRi responders in the venetoclax-LDAC arm and 22% (2/9) in the placebo-LDAC arm received G-CSF post
{"title":"The impact of post-remission granulocyte colony-stimulating factor use in the phase 3 studies of venetoclax combination treatments in patients with newly diagnosed acute myeloid leukemia","authors":"Courtney D. DiNardo, Keith W. Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Árpád Illés, Inho Kim, Vladimir Ivanov, Grace Ku, Catherine L. Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher","doi":"10.1002/ajh.27515","DOIUrl":"https://doi.org/10.1002/ajh.27515","url":null,"abstract":"<p>Based on results from the randomized, placebo-controlled phase 3 VIALE-A (NCT02993523) and VIALE-C (NCT03069352) trials,<span><sup>1-4</sup></span> venetoclax in combination with hypomethylating agents or low-dose cytarabine (LDAC) has become standard of care in patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Cytopenias are common adverse events with venetoclax and are primarily managed with protocol-mandated dose modifications, including dose interruptions and cycle delays.<span><sup>2, 5</sup></span> Neutropenia and febrile neutropenia may be mitigated with granulocyte-colony stimulating factor (G-CSF)<span><sup>4, 6</sup></span>; however, limited evidence exists on G-CSF use and impact on safety and efficacy in patients receiving low-intensity therapies. The present analysis assessed outcomes by G-CSF use post-remission (i.e., following blast clearance) among patients with newly diagnosed, intensive-chemotherapy–ineligible AML who received venetoclax-azacitidine or venetoclax-LDAC in the VIALE-A and VIALE-C trials, respectively.</p>\u0000<p>VIALE-A and VIALE-C study designs have been previously described.<span><sup>1, 3</sup></span> Both trials enrolled patients aged ≥18 years with newly diagnosed AML who were ineligible for induction chemotherapy (aged ≥75 years or with comorbid conditions precluding intensive chemotherapy treatment). In VIALE-A, patients received venetoclax-azacitidine or placebo-azacitidine; in VIALE-C, patients received venetoclax-LDAC or placebo-LDAC. Both trial protocols allowed G-CSF use with administration for cytopenia management as per institutional practice. In this exploratory post hoc analysis, patients treated with venetoclax combinations who had achieved a best response of complete remission (CR)/CR with incomplete hematologic recovery (CRi) were assessed for outcomes by G-CSF use, including overall survival (OS), duration of CR/CRi (DOR), and safety. G-CSF use was analyzed from the time of remission achievement (post-remission), defined as blast clearance (<5% bone marrow blasts) for this analysis. Clinical data cutoff was December 1, 2021 for VIALE-A and February 15, 2021 for VIALE-C.<span><sup>2, 3</sup></span> The analysis populations included patients who achieved best response of CR/CRi, unless otherwise specified.<span><sup>1, 3</sup></span> Data presentation is descriptive in nature, and formal statistical comparisons were not performed due to the post hoc nature of this analysis. Additional details are in the Data S1.</p>\u0000<p>Approximately half of patients treated with venetoclax combinations in VIALE-A and VIALE-C received G-CSF post-remission. In VIALE-A, 50% (95/191) of CR/CRi responders in the venetoclax-azacitidine arm and 26% (11/42) in the placebo-azacitidine arm received G-CSF post-remission (Tables S1 and S2). In VIALE-C, 46% (32/69) of CR/CRi responders in the venetoclax-LDAC arm and 22% (2/9) in the placebo-LDAC arm received G-CSF post","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563290","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}
Naia Oillarburu, Loic Ysebaert, Caroline Protin, Ariadna Ortiz-Brugues, Sarah Baali, Estelle Parriel, Vincent Sibaud
{"title":"Ibrutinib-related stellar hematomas of the palms and soles.","authors":"Naia Oillarburu, Loic Ysebaert, Caroline Protin, Ariadna Ortiz-Brugues, Sarah Baali, Estelle Parriel, Vincent Sibaud","doi":"10.1002/ajh.27514","DOIUrl":"https://doi.org/10.1002/ajh.27514","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556966","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}
Alizée Soulié, Cécile Arnaud, Serge Pissard, Isabelle Hau, Mickaël Shum, Fouad Madhi, Céline Delestrain, Sandra Biscardi, Sabine Blary, Bassem Khazem, Ekaterina Belozertsteva, Eric Guemas, Ralph Epaud, Annie Kamdem, Corinne Pondarré
<p>Acute splenic sequestration crisis (ASSC) is one of the earliest acute clinical manifestations of sickle cell anemia (SCA), with a median age at first episode of 1.8 years [range: 0.4–12.9] as reported for our recently published regional longitudinal newborn cohort, beginning with the introduction of newborn screening (1986) and ending just before the introduction of preventive intensification with hydroxyurea (HU) in 2015.<span><sup>1</sup></span> Early predictive biomarkers have been identified for ASSC, but little is known about the impact of early ASSC on disease severity.<span><sup>2</sup></span> Unlike early dactylitis, early ASSC was not found to be associated with an increase in the risk of adverse outcomes, including death, stroke, frequent vaso-occlusive crisis (VOC), and recurrent acute chest syndrome (ACS), in a cohort of newborns with SCA.<span><sup>3</sup></span></p> <p>Our main objective here was to determine, from our SCA birth cohort, whether children experiencing early ASSC have a higher disease burden. In addition, we aimed to update clinical information on ASSC and confirm the prognostic factors identified in previous studies. Consistent with the French standards of care, for the whole cohort, disease-modifying therapies (DMT) were started only after the occurrence of complications: transfusion program (TP) was mainly implemented for stroke prevention, and HU was prescribed only to children over the age of 3 years for low hemoglobin (Hb) levels and/or recurrence of VOC/ACS. Specifically at our center, TP was offered for frequent VOC/ACS or anemia despite HU, or in children younger than 3 years, and hematopoietic stem cell transplantation (HSCT) to patients with cerebral vasculopathy or frequent VOC/ACS with a human leukocyte antigen-identical sibling. In our cohort-study, the use of DMT was thus considered a surrogate for disease severity.</p> <p>ASSC was defined as splenic enlargement (increase of at least 2 cm from baseline) measured below the costal margin and associated with acute anemia (decrease in Hb concentration >2 g/dL relative to the previous measurement). Early and late ASSC were defined as a first episode of ASSC occurring before or after the age of 2 years respectively. During ASSC, standard management was prompt transfusion to restore effective circulating volume. After the resolution of a first ASSC, local guidelines recommended watchful waiting, unless children had another reason for receiving TP or HU. After the second or third episode, then either splenectomy or a temporary prophylactic TP were considered, to prevent ASSC recurrence. The age at which splenectomy was considered (usually after 3 years of age) and the indication for splenectomy after TP (only if persistent splenomegaly during TP or systematic) varied over time.</p> <p>Children were classified into two groups on the basis of the timing of the first ASSC: before 2 years (early ASSC group), or after 2 years or no ASSC (other group). Descript
{"title":"Prognostic significance of early acute splenic sequestration in children with severe sickle cell genotypes: A comprehensive longitudinal neonatal cohort study","authors":"Alizée Soulié, Cécile Arnaud, Serge Pissard, Isabelle Hau, Mickaël Shum, Fouad Madhi, Céline Delestrain, Sandra Biscardi, Sabine Blary, Bassem Khazem, Ekaterina Belozertsteva, Eric Guemas, Ralph Epaud, Annie Kamdem, Corinne Pondarré","doi":"10.1002/ajh.27517","DOIUrl":"https://doi.org/10.1002/ajh.27517","url":null,"abstract":"<p>Acute splenic sequestration crisis (ASSC) is one of the earliest acute clinical manifestations of sickle cell anemia (SCA), with a median age at first episode of 1.8 years [range: 0.4–12.9] as reported for our recently published regional longitudinal newborn cohort, beginning with the introduction of newborn screening (1986) and ending just before the introduction of preventive intensification with hydroxyurea (HU) in 2015.<span><sup>1</sup></span> Early predictive biomarkers have been identified for ASSC, but little is known about the impact of early ASSC on disease severity.<span><sup>2</sup></span> Unlike early dactylitis, early ASSC was not found to be associated with an increase in the risk of adverse outcomes, including death, stroke, frequent vaso-occlusive crisis (VOC), and recurrent acute chest syndrome (ACS), in a cohort of newborns with SCA.<span><sup>3</sup></span></p>\u0000<p>Our main objective here was to determine, from our SCA birth cohort, whether children experiencing early ASSC have a higher disease burden. In addition, we aimed to update clinical information on ASSC and confirm the prognostic factors identified in previous studies. Consistent with the French standards of care, for the whole cohort, disease-modifying therapies (DMT) were started only after the occurrence of complications: transfusion program (TP) was mainly implemented for stroke prevention, and HU was prescribed only to children over the age of 3 years for low hemoglobin (Hb) levels and/or recurrence of VOC/ACS. Specifically at our center, TP was offered for frequent VOC/ACS or anemia despite HU, or in children younger than 3 years, and hematopoietic stem cell transplantation (HSCT) to patients with cerebral vasculopathy or frequent VOC/ACS with a human leukocyte antigen-identical sibling. In our cohort-study, the use of DMT was thus considered a surrogate for disease severity.</p>\u0000<p>ASSC was defined as splenic enlargement (increase of at least 2 cm from baseline) measured below the costal margin and associated with acute anemia (decrease in Hb concentration >2 g/dL relative to the previous measurement). Early and late ASSC were defined as a first episode of ASSC occurring before or after the age of 2 years respectively. During ASSC, standard management was prompt transfusion to restore effective circulating volume. After the resolution of a first ASSC, local guidelines recommended watchful waiting, unless children had another reason for receiving TP or HU. After the second or third episode, then either splenectomy or a temporary prophylactic TP were considered, to prevent ASSC recurrence. The age at which splenectomy was considered (usually after 3 years of age) and the indication for splenectomy after TP (only if persistent splenomegaly during TP or systematic) varied over time.</p>\u0000<p>Children were classified into two groups on the basis of the timing of the first ASSC: before 2 years (early ASSC group), or after 2 years or no ASSC (other group). Descript","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563324","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}
Srija Shanker, Robert P Hasserjian, Yazan Madanat, Olga K Weinberg, Miguel D Cantu
De novo normal karyotype AML 2017ELN and 2022ELN Genetic Risk Category Changes and Overall Survival in Induction Treated Patients.
新正常核型 AML 2017ELN 和 2022ELN 遗传风险类别变化与诱导治疗患者的总生存率。
{"title":"Impact of myelodysplasia-related mutations on 2022 European LeukemiaNet genetic risk classification in de novo acute myeloid leukemia with normal karyotype.","authors":"Srija Shanker, Robert P Hasserjian, Yazan Madanat, Olga K Weinberg, Miguel D Cantu","doi":"10.1002/ajh.27518","DOIUrl":"https://doi.org/10.1002/ajh.27518","url":null,"abstract":"<p><p>De novo normal karyotype AML 2017ELN and 2022ELN Genetic Risk Category Changes and Overall Survival in Induction Treated Patients.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543149","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":"Harnessing the prognostic potential of PHF6 mutations in chronic myelomonocytic leukemia.","authors":"Francesco Onida","doi":"10.1002/ajh.27512","DOIUrl":"https://doi.org/10.1002/ajh.27512","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520742","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}
Marcus A Carden,Jeffrey Lebensburger,Wayne Rosamond,Paula Tanabe,Vimal K Derebail
{"title":"Emergency department intravenous fluid resuscitation and renal outcomes among adults with sickle cell disease.","authors":"Marcus A Carden,Jeffrey Lebensburger,Wayne Rosamond,Paula Tanabe,Vimal K Derebail","doi":"10.1002/ajh.27509","DOIUrl":"https://doi.org/10.1002/ajh.27509","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488236","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}
Leon D Kaulen,Philipp Karschnia,Sofia Doubrovinskaia,Jeremy S Abramson,Maria Martinez-Lage,Ganesh Shankar,Bryan D Choi,Jeffrey A Barnes,Areej El-Jawahri,Ephraim P Hochberg,P Connor Johnson,Jacob D Soumerai,Wolfgang Wick,Marcela V Maus,Yi-Bin Chen,Matthew J Frigault,Jorg Dietrich
Lymphomatous infiltration of the peripheral nervous system (PNS), termed neurolymphomatosis, represents a distinct extranodal non-Hodgkin lymphoma variant with dismal outcome. CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy has emerged as a safe and effective treatment for B-cell lymphomas. We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis. Neurolymphomatosis patients treated with CD19 CAR T-cells were retrospectively identified at Massachusetts General Hospital over a six-year period. Toxicities were graded according to the ASTCT classification, management, and response rates were recorded. Eleven neurolymphomatosis patients were identified with a median of 2 lines of PNS-directed treatments (range: 1-3) prior to receiving CD19-CAR T-cells. Neurolymphomatosis localized to the nerve roots (8/11, 73%), plexus (5/11, 45%), peripheral (4/11, 36%) and cranial nerves (5/11, 45%). Low grade cytokine release syndrome (CRS) was detected in 8/11 (73%; grade 1: N = 7; grade 2: N = 1) cases. Low- and high-grade immune cell-associated neurotoxicity syndrome (ICANS) were recorded in 5/11 (45%; grade 1: N = 4; grade 2: N = 1) and 1/11 (9%; grade 4) patients, respectively. CRP levels at infusion were predictive of ICANS (area under the curve: 0.96, p = 0.01). Seven of eleven neurolymphomatosis patients (64%) responded to CD19-CAR T-cells. Complete remissions (CR) were achieved in three cases (27%), with 2 patients in sustained CR nine and 46 months after CD19-CAR infusion. Median progression-free survival (PFS) was 4 months. Collectively, CD19-CAR T-cell treatment was well tolerated and showed promising efficacy in recurrent neurolymphomatosis, a difficult to treat condition with unmet medical need. Findings suggest that CD19-CAR may sufficiently penetrate the blood-nerve barrier. Toxicity and outcomes were overall similar to CAR-T cell therapy in CNS lymphoma.
外周神经系统（PNS）的淋巴瘤性浸润被称为神经淋巴瘤病，是一种独特的结节外非霍奇金淋巴瘤变种，其治疗效果令人沮丧。CD19导向嵌合抗原受体（CD19-CAR）T细胞疗法已成为治疗B细胞淋巴瘤的一种安全有效的方法。我们旨在评估 CD19-CAR T 细胞治疗神经淋巴瘤病的毒性和疗效。我们对马萨诸塞州总医院六年来接受 CD19 CAR T 细胞治疗的神经淋巴瘤病患者进行了回顾性鉴定。根据 ASTCT 分类对毒性进行了分级、管理，并记录了反应率。11名神经淋巴瘤病患者在接受CD19-CAR T细胞治疗前接受了中位数为2次的PNS定向治疗（范围：1-3次）。神经淋巴瘤病的病变部位包括神经根（8/11，73%）、神经丛（5/11，45%）、周围神经（4/11，36%）和颅神经（5/11，45%）。8/11（73%；1 级：7 例；2 级：1 例）病例中检测到低级别细胞因子释放综合征（CRS）。5/11（45%；1级：N = 4；2级：N = 1）和1/11（9%；4级）例患者分别出现低级和高级免疫细胞相关神经毒性综合征（ICANS）。输液时的 CRP 水平可预测 ICANS（曲线下面积：0.96，P = 0.01）。11名神经淋巴瘤病患者中有7名（64%）对CD19-CAR T细胞产生了反应。3例患者（27%）获得了完全缓解（CR），其中2例患者在输注CD19-CAR 9个月和46个月后持续获得CR。中位无进展生存期（PFS）为 4 个月。总之，CD19-CAR T细胞治疗耐受性良好，对复发性神经淋巴瘤病有良好疗效，该病治疗困难，医疗需求尚未得到满足。研究结果表明，CD19-CAR可以充分穿透血液-神经屏障。毒性和疗效总体上与中枢神经系统淋巴瘤的CAR-T细胞疗法相似。
{"title":"Toxicities and outcome after CD19-directed chimeric antigen receptor T-cell therapy for secondary neurolymphomatosis.","authors":"Leon D Kaulen,Philipp Karschnia,Sofia Doubrovinskaia,Jeremy S Abramson,Maria Martinez-Lage,Ganesh Shankar,Bryan D Choi,Jeffrey A Barnes,Areej El-Jawahri,Ephraim P Hochberg,P Connor Johnson,Jacob D Soumerai,Wolfgang Wick,Marcela V Maus,Yi-Bin Chen,Matthew J Frigault,Jorg Dietrich","doi":"10.1002/ajh.27505","DOIUrl":"https://doi.org/10.1002/ajh.27505","url":null,"abstract":"Lymphomatous infiltration of the peripheral nervous system (PNS), termed neurolymphomatosis, represents a distinct extranodal non-Hodgkin lymphoma variant with dismal outcome. CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy has emerged as a safe and effective treatment for B-cell lymphomas. We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis. Neurolymphomatosis patients treated with CD19 CAR T-cells were retrospectively identified at Massachusetts General Hospital over a six-year period. Toxicities were graded according to the ASTCT classification, management, and response rates were recorded. Eleven neurolymphomatosis patients were identified with a median of 2 lines of PNS-directed treatments (range: 1-3) prior to receiving CD19-CAR T-cells. Neurolymphomatosis localized to the nerve roots (8/11, 73%), plexus (5/11, 45%), peripheral (4/11, 36%) and cranial nerves (5/11, 45%). Low grade cytokine release syndrome (CRS) was detected in 8/11 (73%; grade 1: N = 7; grade 2: N = 1) cases. Low- and high-grade immune cell-associated neurotoxicity syndrome (ICANS) were recorded in 5/11 (45%; grade 1: N = 4; grade 2: N = 1) and 1/11 (9%; grade 4) patients, respectively. CRP levels at infusion were predictive of ICANS (area under the curve: 0.96, p = 0.01). Seven of eleven neurolymphomatosis patients (64%) responded to CD19-CAR T-cells. Complete remissions (CR) were achieved in three cases (27%), with 2 patients in sustained CR nine and 46 months after CD19-CAR infusion. Median progression-free survival (PFS) was 4 months. Collectively, CD19-CAR T-cell treatment was well tolerated and showed promising efficacy in recurrent neurolymphomatosis, a difficult to treat condition with unmet medical need. Findings suggest that CD19-CAR may sufficiently penetrate the blood-nerve barrier. Toxicity and outcomes were overall similar to CAR-T cell therapy in CNS lymphoma.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488235","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}
Wilma Barcellini, Fabrizio Pane, Andrea Patriarca, Irina Murakhovskaya, Louis Terriou, Maria T DeSancho, Wahid T Hanna, Lance Leopold, Erica Rappold, Ke Szeto, Shaoceng Wei, Ulrich Jäger
Autoimmune hemolytic anemia (AIHA) is a group of acquired autoimmune disorders characterized by red blood cell hemolysis. In a phase 2, open-label, multicenter study, adults with warm AIHA, cold agglutinin disease, or mixed-type AIHA were administered once-daily 1.0 or 2.5 mg parsaclisib (selective phosphoinositide 3-kinase δ inhibitor) orally for 12 weeks, followed by an extension period. Dose increases (for AIHA worsening) or decreases (for tolerability) were permitted. Primary efficacy endpoint was the proportion of patients with complete (≥12 g/dL hemoglobin [Hgb]) or partial (10-12 g/dL Hgb or ≥2 g/dL increase from baseline) response at any visit during weeks 6-12 not attributable to transfusion. Among 25 enrolled patients (median age, 63 y), 16 (64%) achieved a partial or complete Hgb response during weeks 6-12. Responses were observed by week 1 in 52.0% of patients with incremental improvements during weeks 6-12 and sustained responses during the extension period. Responses were higher among patients with warm AIHA versus other types (75.0% vs. 44.4%). Clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue scores were observed at weeks 6 and 12. All patients had treatment-emergent adverse events (TEAEs), most commonly diarrhea (32.0%) and pyrexia (28.0%). Grade ≥3 TEAEs occurred in 13 patients (52.0%). TEAEs considered possibly related to treatment occurred in 11 patients (44.0%). No dose reductions were required; six patients (24%) discontinued for a TEAE. In summary, parsaclisib was well tolerated and resulted in substantial improvements in Hgb response at week 1, with durable responses through the extension period. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT03538041).
{"title":"Parsaclisib for the treatment of primary autoimmune hemolytic anemia: Results from a phase 2, open-label study.","authors":"Wilma Barcellini, Fabrizio Pane, Andrea Patriarca, Irina Murakhovskaya, Louis Terriou, Maria T DeSancho, Wahid T Hanna, Lance Leopold, Erica Rappold, Ke Szeto, Shaoceng Wei, Ulrich Jäger","doi":"10.1002/ajh.27493","DOIUrl":"10.1002/ajh.27493","url":null,"abstract":"<p><p>Autoimmune hemolytic anemia (AIHA) is a group of acquired autoimmune disorders characterized by red blood cell hemolysis. In a phase 2, open-label, multicenter study, adults with warm AIHA, cold agglutinin disease, or mixed-type AIHA were administered once-daily 1.0 or 2.5 mg parsaclisib (selective phosphoinositide 3-kinase δ inhibitor) orally for 12 weeks, followed by an extension period. Dose increases (for AIHA worsening) or decreases (for tolerability) were permitted. Primary efficacy endpoint was the proportion of patients with complete (≥12 g/dL hemoglobin [Hgb]) or partial (10-12 g/dL Hgb or ≥2 g/dL increase from baseline) response at any visit during weeks 6-12 not attributable to transfusion. Among 25 enrolled patients (median age, 63 y), 16 (64%) achieved a partial or complete Hgb response during weeks 6-12. Responses were observed by week 1 in 52.0% of patients with incremental improvements during weeks 6-12 and sustained responses during the extension period. Responses were higher among patients with warm AIHA versus other types (75.0% vs. 44.4%). Clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue scores were observed at weeks 6 and 12. All patients had treatment-emergent adverse events (TEAEs), most commonly diarrhea (32.0%) and pyrexia (28.0%). Grade ≥3 TEAEs occurred in 13 patients (52.0%). TEAEs considered possibly related to treatment occurred in 11 patients (44.0%). No dose reductions were required; six patients (24%) discontinued for a TEAE. In summary, parsaclisib was well tolerated and resulted in substantial improvements in Hgb response at week 1, with durable responses through the extension period. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT03538041).</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456088","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}
Kyo J P H Renshof, Yorick Sandberg, Floor Weerkamp, Barbara J Bain
{"title":"Fulminant intravascular hemolysis resulting from Clostridium perfringens infection.","authors":"Kyo J P H Renshof, Yorick Sandberg, Floor Weerkamp, Barbara J Bain","doi":"10.1002/ajh.27511","DOIUrl":"10.1002/ajh.27511","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456087","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}
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