Pub Date : 2024-09-01Epub Date: 2024-05-02DOI: 10.1080/10428194.2024.2347539
Tareq Abuasab, Shehab Mohamed, Naveen Pemmaraju, Tapan M Kadia, Naval Daver, Courtney D DiNardo, Farhad Ravandi, Wei Qiao, Guillermo Montalban-Bravo, Gautam Borthakur
The presence of BRAF mutation in hematological malignancies, excluding Hairy cell leukemia, and its significance as a driver mutation in myeloid neoplasms (MNs) remains largely understudied. This research aims to evaluate patient characteristics and outcomes of BRAF-mutated MNs. Among a cohort of 6667 patients, 48 (0.7%) had BRAF-mutated MNs. Notably, three patients exhibited sole BRAF mutation, providing evidence supporting the hypothesis of BRAF's role as a driver mutation in MNs. In acute myeloid leukemia, the majority of patients had secondary acute myeloid leukemia, accompanied by poor-risk cytogenic and RAS pathway mutations. Although the acquisition of BRAF mutation during disease progression did not correlate with unfavorable outcomes, its clearance through chemotherapy or stem cell transplant exhibited favorable outcomes (median overall survival of 34.8 months versus 10.4 months, p = 0.047). Furthermore, G469A was the most frequently observed BRAF mutation, differing from solid tumors and hairy cell leukemia, where V600E mutations were predominant.
{"title":"<i>BRAF</i> mutation in myeloid neoplasm: incidences and clinical outcomes.","authors":"Tareq Abuasab, Shehab Mohamed, Naveen Pemmaraju, Tapan M Kadia, Naval Daver, Courtney D DiNardo, Farhad Ravandi, Wei Qiao, Guillermo Montalban-Bravo, Gautam Borthakur","doi":"10.1080/10428194.2024.2347539","DOIUrl":"10.1080/10428194.2024.2347539","url":null,"abstract":"<p><p>The presence of <i>BRAF</i> mutation in hematological malignancies, excluding Hairy cell leukemia, and its significance as a driver mutation in myeloid neoplasms (MNs) remains largely understudied. This research aims to evaluate patient characteristics and outcomes of <i>BRAF</i>-mutated MNs. Among a cohort of 6667 patients, 48 (0.7%) had <i>BRAF</i>-mutated MNs. Notably, three patients exhibited sole <i>BRAF</i> mutation, providing evidence supporting the hypothesis of <i>BRAF</i>'s role as a driver mutation in MNs. In acute myeloid leukemia, the majority of patients had secondary acute myeloid leukemia, accompanied by poor-risk cytogenic and RAS pathway mutations. Although the acquisition of <i>BRAF</i> mutation during disease progression did not correlate with unfavorable outcomes, its clearance through chemotherapy or stem cell transplant exhibited favorable outcomes (median overall survival of 34.8 months versus 10.4 months, <i>p</i> = 0.047). Furthermore, G469A was the most frequently observed <i>BRAF</i> mutation, differing from solid tumors and hairy cell leukemia, where V600E mutations were predominant.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The survival rate of non-Hodgkin lymphoma (NHL) has steadily improved. However, osteoporosis introduced by treatment is prevalent and associated with increased mortality and disability for patients with NHL. We aimed to investigate factors impacting bone mineral density (BMD) reduction and osteoporosis, and the trend of BMD after chemotherapy. Overall, 97 newly diagnosed patients with follicular lymphoma (FL) were retrospectively enrolled. CT attenuation values were measured to assess BMD levels. Although 73.2% of patients received calcium and vitamin D supplements, 44.3% showed significant BMD reduction, and baseline BMD and hemoglobin levels were the risk factors. 26.6% of patients newly developed osteoporosis post-chemotherapy where age and cumulative dose of glucocorticoid were risk factors. The results of 20 patients with consecutive follow-up showed that BMD continued to decline for 6 months post-chemotherapy and did not return to baseline values. Therefore, BMD evaluation and more positive anti-resorption treatments should be administered for high-risk patients.
非霍奇金淋巴瘤(NHL)的存活率稳步提高。然而,治疗引起的骨质疏松症在 NHL 患者中十分普遍,并与死亡率和残疾率的增加有关。我们旨在研究影响骨矿物质密度(BMD)降低和骨质疏松症的因素,以及化疗后骨矿物质密度的变化趋势。我们回顾性地纳入了97名新确诊的滤泡性淋巴瘤(FL)患者。通过测量CT衰减值来评估BMD水平。虽然73.2%的患者接受了钙和维生素D补充剂治疗,但44.3%的患者BMD明显下降,而基线BMD和血红蛋白水平是风险因素。26.6%的患者在化疗后新出现骨质疏松症,年龄和糖皮质激素累积剂量是风险因素。对 20 例患者的连续随访结果显示,化疗后 6 个月内,BMD 持续下降,且未恢复至基线值。因此,对高危患者应进行 BMD 评估并采取更积极的抗骨质吸收治疗。
{"title":"Risk factors for treatment-related bone loss and osteoporosis in patients with follicular lymphoma.","authors":"Yong Xing, Kaifeng Ye, Chunyuan Li, Jinyao He, Fei Dong, Yun Tian","doi":"10.1080/10428194.2024.2348113","DOIUrl":"10.1080/10428194.2024.2348113","url":null,"abstract":"<p><p>The survival rate of non-Hodgkin lymphoma (NHL) has steadily improved. However, osteoporosis introduced by treatment is prevalent and associated with increased mortality and disability for patients with NHL. We aimed to investigate factors impacting bone mineral density (BMD) reduction and osteoporosis, and the trend of BMD after chemotherapy. Overall, 97 newly diagnosed patients with follicular lymphoma (FL) were retrospectively enrolled. CT attenuation values were measured to assess BMD levels. Although 73.2% of patients received calcium and vitamin D supplements, 44.3% showed significant BMD reduction, and baseline BMD and hemoglobin levels were the risk factors. 26.6% of patients newly developed osteoporosis post-chemotherapy where age and cumulative dose of glucocorticoid were risk factors. The results of 20 patients with consecutive follow-up showed that BMD continued to decline for 6 months post-chemotherapy and did not return to baseline values. Therefore, BMD evaluation and more positive anti-resorption treatments should be administered for high-risk patients.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-15DOI: 10.1080/10428194.2024.2354527
Paul Wadsworth, Jingjing Zhang, Timothy Miller, Joshua Menke, Jean Oak, Sebastian Fernandez-Pol
{"title":"Prevalence and clinicopathological features of incidentally detected TRBC1-dim populations in peripheral blood flow cytometry.","authors":"Paul Wadsworth, Jingjing Zhang, Timothy Miller, Joshua Menke, Jean Oak, Sebastian Fernandez-Pol","doi":"10.1080/10428194.2024.2354527","DOIUrl":"10.1080/10428194.2024.2354527","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-05DOI: 10.1080/10428194.2024.2346733
Vikas Gupta, Abdulraheem Yacoub, Ruben A Mesa, Claire N Harrison, Alessandro M Vannucchi, Jean-Jacques Kiladjian, Hans-Joachim Deeg, Salman Fazal, Lynda Foltz, Ryan J Mattison, Carole B Miller, Vinod Parameswaran, Patrick Brown, Christopher Hernandez, Jia Wang, Moshe Talpaz
The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet count ≥50 × 109/L, previously treated with ruxolitinib. The trial design included protocol specified strategies to mitigate the risk for gastrointestinal (GI) adverse events (AEs), thiamine supplementation, and encephalopathy surveillance. Due to COVID-19, accrual was cut short with 38 patients enrolled. In the efficacy evaluable population (n = 35), nine (25.7%; 95% confidence interval 12.5-43.3) patients achieved primary endpoint of ≥35% spleen volume reduction (SVR) at end of cycle (EOC) 6; and 22 (62.9%) patients showed best overall response of ≥35% SVR up to end of treatment. Sixteen (44.4%) patients showed ≥50% reduction in total symptom score at EOC6 (n = 36). Compared to previously reported JAKARTA-2 trial, rates of GI AEs were lower, and no patient developed encephalopathy. Overall, FREEDOM study showed clinically relevant spleen and symptom responses with fedratinib, and effective mitigation of GI AEs.
{"title":"Safety and efficacy of fedratinib in patients with myelofibrosis previously treated with ruxolitinib: primary analysis of FREEDOM trial.","authors":"Vikas Gupta, Abdulraheem Yacoub, Ruben A Mesa, Claire N Harrison, Alessandro M Vannucchi, Jean-Jacques Kiladjian, Hans-Joachim Deeg, Salman Fazal, Lynda Foltz, Ryan J Mattison, Carole B Miller, Vinod Parameswaran, Patrick Brown, Christopher Hernandez, Jia Wang, Moshe Talpaz","doi":"10.1080/10428194.2024.2346733","DOIUrl":"10.1080/10428194.2024.2346733","url":null,"abstract":"<p><p>The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet count ≥50 × 10<sup>9</sup>/L, previously treated with ruxolitinib. The trial design included protocol specified strategies to mitigate the risk for gastrointestinal (GI) adverse events (AEs), thiamine supplementation, and encephalopathy surveillance. Due to COVID-19, accrual was cut short with 38 patients enrolled. In the efficacy evaluable population (<i>n</i> = 35), nine (25.7%; 95% confidence interval 12.5-43.3) patients achieved primary endpoint of ≥35% spleen volume reduction (SVR) at end of cycle (EOC) 6; and 22 (62.9%) patients showed best overall response of ≥35% SVR up to end of treatment. Sixteen (44.4%) patients showed ≥50% reduction in total symptom score at EOC6 (<i>n</i> = 36). Compared to previously reported JAKARTA-2 trial, rates of GI AEs were lower, and no patient developed encephalopathy. Overall, FREEDOM study showed clinically relevant spleen and symptom responses with fedratinib, and effective mitigation of GI AEs.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-15DOI: 10.1080/10428194.2024.2353330
Fabien Despas, Maria Chaouki, Sandra de Barros, Baptiste Bonneau, Ben Allal, Julie Guillermet-Guibert, Loïc Ysebaert
{"title":"Pharmacokinetics of idelalisib in chronic lymphocytic leukemia and follicular lymphoma disclose better outcomes for patients with lower exposure.","authors":"Fabien Despas, Maria Chaouki, Sandra de Barros, Baptiste Bonneau, Ben Allal, Julie Guillermet-Guibert, Loïc Ysebaert","doi":"10.1080/10428194.2024.2353330","DOIUrl":"10.1080/10428194.2024.2353330","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-07DOI: 10.1080/10428194.2024.2344061
Georgina Gener-Ricos, Juan Jose Rodriguez-Sevilla, Samuel Urrutia, Alex Bataller, Alexandre Bazinet, Guillermo Garcia-Manero
Higher-risk myelodysplastic syndromes (HR-MDS) are defined using a number of prognostic scoring systems that include the degree of cytopenias, percentage of blasts, cytogenetic alterations, and more recently genomic data. HR-MDS encompasses characteristics such as progressive cytopenias, increased bone marrow blasts, unfavorable cytogenetics, and an adverse mutational profile. Survival is generally poor, and patients require therapy to improve outcomes. Hypomethylating agents (HMAs), such as azacitidine, decitabine, and more recently, oral decitabine/cedazuridine, are the only approved therapies for HR-MDS. These are often continued until loss of response, progression, or unacceptable toxicity. Combinations including an HMA plus other drugs have been investigated but have not demonstrated better outcomes compared to single-agent HMA. Moreover, in a disease of high genomic complexity such as HR-MDS, therapy targeting specific genomic abnormalities is of interest. This review will examine the biological underpinnings of HR-MDS, its therapeutic landscape in the frontline and relapsed settings, as well as the impact of hematopoietic stem cell transplantation, the only known curative intervention for this disease.
{"title":"Advances in the management of higher-risk myelodysplastic syndromes: future prospects.","authors":"Georgina Gener-Ricos, Juan Jose Rodriguez-Sevilla, Samuel Urrutia, Alex Bataller, Alexandre Bazinet, Guillermo Garcia-Manero","doi":"10.1080/10428194.2024.2344061","DOIUrl":"10.1080/10428194.2024.2344061","url":null,"abstract":"<p><p>Higher-risk myelodysplastic syndromes (HR-MDS) are defined using a number of prognostic scoring systems that include the degree of cytopenias, percentage of blasts, cytogenetic alterations, and more recently genomic data. HR-MDS encompasses characteristics such as progressive cytopenias, increased bone marrow blasts, unfavorable cytogenetics, and an adverse mutational profile. Survival is generally poor, and patients require therapy to improve outcomes. Hypomethylating agents (HMAs), such as azacitidine, decitabine, and more recently, oral decitabine/cedazuridine, are the only approved therapies for HR-MDS. These are often continued until loss of response, progression, or unacceptable toxicity. Combinations including an HMA plus other drugs have been investigated but have not demonstrated better outcomes compared to single-agent HMA. Moreover, in a disease of high genomic complexity such as HR-MDS, therapy targeting specific genomic abnormalities is of interest. This review will examine the biological underpinnings of HR-MDS, its therapeutic landscape in the frontline and relapsed settings, as well as the impact of hematopoietic stem cell transplantation, the only known curative intervention for this disease.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-22DOI: 10.1080/10428194.2024.2351194
Karolina Bełdzińska-Gądek, Ewa Zarzycka, Krzysztof Pastuszak, Katarzyna Borman, Krzysztof Lewandowski, Jan M Zaucha, Witold Prejzner
Acute leukemia (AL) with a lineage switch (LS) is associated with poor prognosis. The predisposing factors of LS are unknown, apart from KMT2A rearrangements that have been reported to be associated with LS. Herein, we present two cases and review all 104 published cases to identify risk factors for LS. Most of the patients (75.5%) experienced a switch from the lymphoid phenotype to the myeloid phenotype. Eighteen patients (17.0%) experienced a transformation from acute myelogenous leukemia (AML) to acute lymphoblastic leukemia (ALL). Forty-nine (46.2%) patients carried a KMT2A rearrangement. Most of the cases involved LS from B-cell ALL (B-ALL) to AML (59.4%), and 49 patients (46.2%) carried KMT2A-rearrangements. Forty patients (37.7%) received lineage-specific immunotherapy. Our findings suggest that the prevalence of KMT2A rearrangements together with the lineage-specific immunotherapy may trigger LS, which supports the thesis of the existence of leukemia stem cells that are capable of lymphoid or myeloid differentiation.
伴有血系转换(LS)的急性白血病(AL)预后不良。除了有报道称KMT2A重排与LS相关外,LS的致病因素尚不清楚。在此,我们介绍了两个病例,并回顾了所有已发表的 104 个病例,以确定 LS 的风险因素。大多数患者(75.5%)经历了从淋巴表型向髓表型的转变。18名患者(17.0%)从急性髓性白血病(AML)转变为急性淋巴细胞白血病(ALL)。49名患者(46.2%)携带KMT2A重排。大多数病例涉及从B细胞ALL(B-ALL)到AML的LS(59.4%),49名患者(46.2%)携带KMT2A重排。40名患者(37.7%)接受了系特异性免疫治疗。我们的研究结果表明,KMT2A重排的发生率加上系特异性免疫疗法可能会引发LS,这支持了白血病干细胞能够进行淋巴或髓系分化的论点。
{"title":"Immune escape of B-cell lymphoblastic leukemic cells through a lineage switch to acute myeloid leukemia.","authors":"Karolina Bełdzińska-Gądek, Ewa Zarzycka, Krzysztof Pastuszak, Katarzyna Borman, Krzysztof Lewandowski, Jan M Zaucha, Witold Prejzner","doi":"10.1080/10428194.2024.2351194","DOIUrl":"10.1080/10428194.2024.2351194","url":null,"abstract":"<p><p>Acute leukemia (AL) with a lineage switch (LS) is associated with poor prognosis. The predisposing factors of LS are unknown, apart from <i>KMT2A</i> rearrangements that have been reported to be associated with LS. Herein, we present two cases and review all 104 published cases to identify risk factors for LS. Most of the patients (75.5%) experienced a switch from the lymphoid phenotype to the myeloid phenotype. Eighteen patients (17.0%) experienced a transformation from acute myelogenous leukemia (AML) to acute lymphoblastic leukemia (ALL). Forty-nine (46.2%) patients carried a <i>KMT2A</i> rearrangement. Most of the cases involved LS from B-cell ALL (B-ALL) to AML (59.4%), and 49 patients (46.2%) carried <i>KMT2A</i>-rearrangements. Forty patients (37.7%) received lineage-specific immunotherapy. Our findings suggest that the prevalence of <i>KMT2A</i> rearrangements together with the lineage-specific immunotherapy may trigger LS, which supports the thesis of the existence of leukemia stem cells that are capable of lymphoid or myeloid differentiation.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-23DOI: 10.1080/10428194.2024.2353879
Netanel A Horowitz, Ali Abed Al Wahad, Noam P Bettman, Shimrit Ringelstein-Harlev, Benjamin Brenner, Tami Katz
{"title":"Acceleration of non-Hodgkin lymphoma progression during pregnancy in a murine model.","authors":"Netanel A Horowitz, Ali Abed Al Wahad, Noam P Bettman, Shimrit Ringelstein-Harlev, Benjamin Brenner, Tami Katz","doi":"10.1080/10428194.2024.2353879","DOIUrl":"10.1080/10428194.2024.2353879","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The present study aimed to investigate the real-world results of childhood acute lymphoblastic leukemia (cALL) cases in Fujian, China. The clinical data of 1414 patients with newly diagnosed cALL in Fujian were retrospectively analyzed. Patients were treated according to the Chinese Children Leukemia Group 2008 protocol (CCLG-ALL 2008 group) or Chinese Children's Cancer Group 2015 protocol (CCCG-ALL 2015 group). Cumulative incidence of treatment abandonment (TA) at 5 years was 4.2% ± 0.6% and significantly associated with treatment period and risk stratification. The 5-OS and EFS were significantly higher in the CCCG-ALL 2015 group than in the CCLG-ALL 2008 group. Patients treated with CCCG-ALL 2015 from Fujian Medical Union Hospital had a significantly higher 4-year OS and EFS than did those from the other four hospitals. Real-world TA of cALL greatly decreased, and its long-term survival significantly increased in Fujian, which may be related to optimizing programs, multi-center collaboration, and improving treatment compliance.
{"title":"Experience in improving treatment outcomes for childhood acute lymphoblastic leukemia: real-world results for a province in China, 2011-2020.","authors":"Yongzhi Zheng, Jiazheng Li, Hong Wen, Kaizhi Weng, Shuquan Zhuang, Xingguo Wu, Jian Li, Hao Zheng, Xueling Hua, Zaisheng Chen, Jianda Hu, Shaohua Le","doi":"10.1080/10428194.2024.2350665","DOIUrl":"10.1080/10428194.2024.2350665","url":null,"abstract":"<p><p>The present study aimed to investigate the real-world results of childhood acute lymphoblastic leukemia (cALL) cases in Fujian, China. The clinical data of 1414 patients with newly diagnosed cALL in Fujian were retrospectively analyzed. Patients were treated according to the Chinese Children Leukemia Group 2008 protocol (CCLG-ALL 2008 group) or Chinese Children's Cancer Group 2015 protocol (CCCG-ALL 2015 group). Cumulative incidence of treatment abandonment (TA) at 5 years was 4.2% ± 0.6% and significantly associated with treatment period and risk stratification. The 5-OS and EFS were significantly higher in the CCCG-ALL 2015 group than in the CCLG-ALL 2008 group. Patients treated with CCCG-ALL 2015 from Fujian Medical Union Hospital had a significantly higher 4-year OS and EFS than did those from the other four hospitals. Real-world TA of cALL greatly decreased, and its long-term survival significantly increased in Fujian, which may be related to optimizing programs, multi-center collaboration, and improving treatment compliance.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-07DOI: 10.1080/10428194.2024.2346755
Farhad Ravandi, Marion Subklewe, Roland B Walter, Pankit Vachhani, Gert Ossenkoppele, Veit Buecklein, Hartmut Döhner, Mojca Jongen-Lavrencic, Claudia D Baldus, Lars Fransecky, Timothy S Pardee, Hagop Kantarjian, Priscilla K Yen, Lata Mukundan, Bharat Panwar, Marc R Yago, Suresh Agarwal, Sophia K Khaldoyanidi, Anthony Stein
AMG 330, a bispecific T-cell engager (BiTE®) that binds CD33 and CD3 on T cells facilitates T-cell-mediated cytotoxicity against CD33+ cells. This first-in-human, open-label, dose-escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMG 330 in adults with relapsed/refractory acute myeloid leukemia (R/R AML). Amongst 77 patients treated with AMG 330 (0.5 µg/day-1.6 mg/day) on 14-day or 28-day cycles, maximum tolerated dose was not reached; median duration of treatment was 29 days. The most frequent treatment-related adverse events were cytokine release syndrome (CRS; 78%) and rash (30%); 10% of patients experienced grade 3/4 CRS. CRS was mitigated with stepwise dosing of AMG 330, prophylactic dexamethasone, and early treatment with tocilizumab. Among 60 evaluable patients, eight achieved complete remission or morphologic leukemia-free state; of the 52 non-responders, 37% had ≥50% reduction in AML bone marrow blasts. AMG 330 is a promising CD33-targeted therapeutic strategy for R/R AML.
AMG 330 是一种双特异性 T 细胞吸引剂 (BiTE®),能与 T 细胞上的 CD33 和 CD3 结合,促进 T 细胞介导的针对 CD33+ 细胞的细胞毒性。这项首例人体开放标签剂量递增研究评估了AMG 330在复发/难治性急性髓性白血病(R/R AML)成人患者中的安全性、药代动力学、药效学和初步疗效。在77名接受AMG 330(0.5微克/天-1.6毫克/天)治疗的患者中,治疗周期为14天或28天,均未达到最大耐受剂量;中位治疗时间为29天。最常见的治疗相关不良事件是细胞因子释放综合征(CRS;78%)和皮疹(30%);10%的患者出现3/4级CRS。通过逐步服用AMG 330、预防性地塞米松和早期使用托珠单抗治疗,CRS得到了缓解。在60名可评估的患者中,有8人获得了完全缓解或无形态白血病状态;在52名无应答者中,有37%的急性髓细胞性白血病骨髓细胞数减少了≥50%。AMG 330是治疗R/R急性髓细胞性白血病的一种前景看好的CD33靶向治疗策略。
{"title":"Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study.","authors":"Farhad Ravandi, Marion Subklewe, Roland B Walter, Pankit Vachhani, Gert Ossenkoppele, Veit Buecklein, Hartmut Döhner, Mojca Jongen-Lavrencic, Claudia D Baldus, Lars Fransecky, Timothy S Pardee, Hagop Kantarjian, Priscilla K Yen, Lata Mukundan, Bharat Panwar, Marc R Yago, Suresh Agarwal, Sophia K Khaldoyanidi, Anthony Stein","doi":"10.1080/10428194.2024.2346755","DOIUrl":"10.1080/10428194.2024.2346755","url":null,"abstract":"<p><p>AMG 330, a bispecific T-cell engager (BiTE®) that binds CD33 and CD3 on T cells facilitates T-cell-mediated cytotoxicity against CD33+ cells. This first-in-human, open-label, dose-escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMG 330 in adults with relapsed/refractory acute myeloid leukemia (R/R AML). Amongst 77 patients treated with AMG 330 (0.5 µg/day-1.6 mg/day) on 14-day or 28-day cycles, maximum tolerated dose was not reached; median duration of treatment was 29 days. The most frequent treatment-related adverse events were cytokine release syndrome (CRS; 78%) and rash (30%); 10% of patients experienced grade 3/4 CRS. CRS was mitigated with stepwise dosing of AMG 330, prophylactic dexamethasone, and early treatment with tocilizumab. Among 60 evaluable patients, eight achieved complete remission or morphologic leukemia-free state; of the 52 non-responders, 37% had ≥50% reduction in AML bone marrow blasts. AMG 330 is a promising CD33-targeted therapeutic strategy for R/R AML.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}