Rong Wang, Yi Zhang, Jie Chang, Huafeng Wang, Yinjun Lou, Min Yang, Gaixiang Xu, Hongyan Tong, Wanzhuo Xie, De Zhou, Juying Wei, Wenyuan Mai, Xiujin Ye, Haitao Meng, Jie Jin, Hong-Hu Zhu
Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy (DAV) has shown safety and efficacy in eligible patients with newly diagnosed acute myeloid leukemia (AML). However, there are no direct comparisons between DAV and 3 + 7 daunorubicin and cytarabine chemotherapy (DA) alone. We performed a propensity score-matched analysis to compare the outcomes of DAV group with historical DA group and identify the clinical and molecular characteristics of patients who might benefit from the DAV regimen. The DAV group had a higher Complete remission (CR) rate than the DA group (90% vs. 55%, p = 0.008). 25 (96%) patients in the DAV group had a higher MRD-negative CRc rate compared with 13 (62%) patients in the DA group (p = 0.006). After a median follow-up duration of 19.15 (IQR 17.13–21.67) months, the DAV group had an improved overall survival (p = 0.001) and event-free survival (p = 0.069), but not disease-free survival (p = 0.136). Collectively, DAV regimen induced high CR rates and deep MRD-negative CRc rates after one cycle of induction therapy, as well as prolonged the overall survival, in young adult patients with AML who were eligible for intensive chemotherapy. The addition of venetoclax to intensive chemotherapy should be considered in the future to achieve better survival advantages in eligible AML patients.
{"title":"Venetoclax plus daunorubicin and cytarabine in newly diagnosed acute myeloid leukemia patients: A propensity score-matched analysis","authors":"Rong Wang, Yi Zhang, Jie Chang, Huafeng Wang, Yinjun Lou, Min Yang, Gaixiang Xu, Hongyan Tong, Wanzhuo Xie, De Zhou, Juying Wei, Wenyuan Mai, Xiujin Ye, Haitao Meng, Jie Jin, Hong-Hu Zhu","doi":"10.1002/hon.3260","DOIUrl":"10.1002/hon.3260","url":null,"abstract":"<p>Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy (DAV) has shown safety and efficacy in eligible patients with newly diagnosed acute myeloid leukemia (AML). However, there are no direct comparisons between DAV and 3 + 7 daunorubicin and cytarabine chemotherapy (DA) alone. We performed a propensity score-matched analysis to compare the outcomes of DAV group with historical DA group and identify the clinical and molecular characteristics of patients who might benefit from the DAV regimen. The DAV group had a higher Complete remission (CR) rate than the DA group (90% vs. 55%, <i>p</i> = 0.008). 25 (96%) patients in the DAV group had a higher MRD-negative CRc rate compared with 13 (62%) patients in the DA group (<i>p</i> = 0.006). After a median follow-up duration of 19.15 (IQR 17.13–21.67) months, the DAV group had an improved overall survival (<i>p</i> = 0.001) and event-free survival (<i>p</i> = 0.069), but not disease-free survival (<i>p</i> = 0.136). Collectively, DAV regimen induced high CR rates and deep MRD-negative CRc rates after one cycle of induction therapy, as well as prolonged the overall survival, in young adult patients with AML who were eligible for intensive chemotherapy. The addition of venetoclax to intensive chemotherapy should be considered in the future to achieve better survival advantages in eligible AML patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982809","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}
Thierry Facon, Philippe Moreau, Ivan Špicka, Kenshi Suzuki, Kwee Yong, Joseph Mikhael, Taro Fukao, Kamlesh Bisht, Nicole M. Armstrong, Sandrine Macé, Marie-Laure Risse, Thomas Martin
Gain/amplification of 1q21 (≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma, can negatively affect prognosis, due to its involvement in resistance to anti-myeloma therapy and disease progression. In this updated subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285) in relapsed/refractory multiple myeloma (RRMM), we evaluated progression-free survival (PFS) and depth of response with the anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) versus Kd, in 1q21+ patients and related subgroups, at long-term follow-up (44.2 months). Our analysis included patients with 1q21+ (≥3 copies, with/without high-risk chromosomal abnormality [HRCA]), isolated 1q21+ (≥3 copies, without HRCA), gain(1q21) (3 copies, with/without HRCA), and amp(1q21) (≥4 copies, with/without HRCA). PFS benefit was achieved with Isa-Kd versus Kd in patients with 1q21+ (HR 0.58, 95% CI: 0.37–0.92), with isolated 1q21+ (HR 0.49, 95% CI: 0.27–0.92), with gain(1q21), or amp(1q21), consistent with the overall population and prior interim 1q21+ subgroup analyses. Median PFS with Isa-Kd versus Kd was 25.8 versus 16.2 months in 1q21+ patients and 38.2 versus 16.2 months in patients with isolated 1q21+. Clinically meaningful, higher rates of very good partial response or better, complete response or better (≥CR), minimal residual disease (MRD) negativity, and MRD negativity and ≥CR were reached with Isa-Kd versus Kd in patients with 1q21+, isolated 1q21+, gain(1q21), or amp(1q21). In Isa-Kd and Kd, the MRD negativity and ≥CR rate was 29.3% versus 15.4% in 1q21+ patients, 36.2% versus 12.9% in patients with isolated 1q21+, 27.9% versus 13.5% in patients with gain(1q21), and 31.3% versus 20.0% in patients with amp(1q21), respectively. In conclusion, addition of Isa to Kd in triplet combination therapy has shown PFS benefit and deeper responses, compared with Kd, in 1q21+ patients at higher risk of progression, including patients with isolated 1q21+, gain(1q21), and amp(1q21), thus supporting Isa-Kd an effective treatment option for patients with RRMM.
{"title":"Isatuximab in combination with carfilzomib and dexamethasone in 1q21+ patients with relapsed/refractory multiple myeloma: Long-term outcomes in the Phase 3 IKEMA study","authors":"Thierry Facon, Philippe Moreau, Ivan Špicka, Kenshi Suzuki, Kwee Yong, Joseph Mikhael, Taro Fukao, Kamlesh Bisht, Nicole M. Armstrong, Sandrine Macé, Marie-Laure Risse, Thomas Martin","doi":"10.1002/hon.3258","DOIUrl":"10.1002/hon.3258","url":null,"abstract":"<p>Gain/amplification of 1q21 (≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma, can negatively affect prognosis, due to its involvement in resistance to anti-myeloma therapy and disease progression. In this updated subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285) in relapsed/refractory multiple myeloma (RRMM), we evaluated progression-free survival (PFS) and depth of response with the anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) versus Kd, in 1q21+ patients and related subgroups, at long-term follow-up (44.2 months). Our analysis included patients with 1q21+ (≥3 copies, with/without high-risk chromosomal abnormality [HRCA]), isolated 1q21+ (≥3 copies, without HRCA), gain(1q21) (3 copies, with/without HRCA), and amp(1q21) (≥4 copies, with/without HRCA). PFS benefit was achieved with Isa-Kd versus Kd in patients with 1q21+ (HR 0.58, 95% CI: 0.37–0.92), with isolated 1q21+ (HR 0.49, 95% CI: 0.27–0.92), with gain(1q21), or amp(1q21), consistent with the overall population and prior interim 1q21+ subgroup analyses. Median PFS with Isa-Kd versus Kd was 25.8 versus 16.2 months in 1q21+ patients and 38.2 versus 16.2 months in patients with isolated 1q21+. Clinically meaningful, higher rates of very good partial response or better, complete response or better (≥CR), minimal residual disease (MRD) negativity, and MRD negativity and ≥CR were reached with Isa-Kd versus Kd in patients with 1q21+, isolated 1q21+, gain(1q21), or amp(1q21). In Isa-Kd and Kd, the MRD negativity and ≥CR rate was 29.3% versus 15.4% in 1q21+ patients, 36.2% versus 12.9% in patients with isolated 1q21+, 27.9% versus 13.5% in patients with gain(1q21), and 31.3% versus 20.0% in patients with amp(1q21), respectively. In conclusion, addition of Isa to Kd in triplet combination therapy has shown PFS benefit and deeper responses, compared with Kd, in 1q21+ patients at higher risk of progression, including patients with isolated 1q21+, gain(1q21), and amp(1q21), thus supporting Isa-Kd an effective treatment option for patients with RRMM.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Duminuco, Antonella Nardo, Giuseppe A. Palumbo
{"title":"Occurrence of lymphoproliferative disorders during ruxolitinib treatment: May fedratinib be the turning point?","authors":"Andrea Duminuco, Antonella Nardo, Giuseppe A. Palumbo","doi":"10.1002/hon.3259","DOIUrl":"10.1002/hon.3259","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944078","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}
This study aimed to investigate the clinical characteristics and prognosis of Runt-related transcription factor 1 (RUNX1) mutant acute myeloid leukemia (AML) patients by comparing the features of AML patients with or without RUNX1 mutation. We retrospectively analyzed 180 AML patients including 36 AML patients with mutant RUNX1(AML-RUNX1mut) and 144 AML patients with wild-type RUNX1(AML-RUNX1wt) were selected using the case-pair method(1:4). Compared to AML-RUNX1wt, AML-RUNX1mut showed higher frequency of ASXL1 (p < 0.001), SRSF2 (p < 0.001), BCORL1 (p < 0.001), RAS (p = 0.010) mutations, and absent NPM1 mutations (p = 0.022). The 3-year overall survival (OS) and disease-free survival (DFS) of AML-RUNX1mut and AML-RUNX1wt were 73.1% versus 68.0% (p = 0.64) and 80.7% versus 71.6% (p = 0.37), respectively. AML-RUNX1mut receiving allogeneic hematopoietic cell transplantation (allo-HSCT) showed better survival than those who did not receive allo-HSCT (3-year OS, 84.3% vs. 52.7%; p = 0.006). Multivariate analysis showed that EZH2 mutation (p = 0.003), white blood cell (WBC) ≥30 × 109/L (p = 0.036) and age ≥60 years (p = 0.038) were significant independent risk factors for inferior OS of AML-RUNX1mut; WBC ≥30 × 109/L (p = 0.013) and DNMT3A mutation (p = 0.045) were significant independent risk factors for shorter DFS of AML-RUNX1mut. In conclusion, AML-RUNX1mut showed unique clinical characteristics, but the survival between AML-RUNX1mut and AML-RUNX1wt were comparable. EZH2 co-mutation, DNMT3A co-mutation, old age and high WBC count were associated with inferior survival of AML-RUNX1mut. Allo-HSCT can significantly improve the prognosis of AML-RUNX1mut.
{"title":"Clinical characteristics and prognosis of acute myeloid leukemia patients with Runt-related transcription factor 1 mutation: A single-center retrospective analysis","authors":"Lin-Ya Wang, Yao Li, Qian Jiang, Hao Jiang, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Fei-Fei Tang","doi":"10.1002/hon.3256","DOIUrl":"10.1002/hon.3256","url":null,"abstract":"<p>This study aimed to investigate the clinical characteristics and prognosis of Runt-related transcription factor 1 (RUNX1) mutant acute myeloid leukemia (AML) patients by comparing the features of AML patients with or without RUNX1 mutation. We retrospectively analyzed 180 AML patients including 36 AML patients with mutant RUNX1(AML-RUNX1<sup>mut</sup>) and 144 AML patients with wild-type RUNX1(AML-RUNX1<sup>wt</sup>) were selected using the case-pair method(1:4). Compared to AML-RUNX1<sup>wt</sup>, AML-RUNX1<sup>mut</sup> showed higher frequency of ASXL1 (<i>p</i> < 0.001), SRSF2 (<i>p</i> < 0.001), BCORL1 (<i>p</i> < 0.001), RAS (<i>p</i> = 0.010) mutations, and absent NPM1 mutations (<i>p</i> = 0.022). The 3-year overall survival (OS) and disease-free survival (DFS) of AML-RUNX1<sup>mut</sup> and AML-RUNX1<sup>wt</sup> were 73.1% versus 68.0% (<i>p</i> = 0.64) and 80.7% versus 71.6% (<i>p</i> = 0.37), respectively. AML-RUNX1<sup>mut</sup> receiving allogeneic hematopoietic cell transplantation (allo-HSCT) showed better survival than those who did not receive allo-HSCT (3-year OS, 84.3% vs. 52.7%; <i>p</i> = 0.006). Multivariate analysis showed that EZH2 mutation (<i>p</i> = 0.003), white blood cell (WBC) ≥30 × 10<sup>9</sup>/L (<i>p</i> = 0.036) and age ≥60 years (<i>p</i> = 0.038) were significant independent risk factors for inferior OS of AML-RUNX1<sup>mut</sup>; WBC ≥30 × 10<sup>9</sup>/L (<i>p</i> = 0.013) and DNMT3A mutation (<i>p</i> = 0.045) were significant independent risk factors for shorter DFS of AML-RUNX1<sup>mut</sup>. In conclusion, AML-RUNX1<sup>mut</sup> showed unique clinical characteristics, but the survival between AML-RUNX1<sup>mut</sup> and AML-RUNX1<sup>wt</sup> were comparable. EZH2 co-mutation, DNMT3A co-mutation, old age and high WBC count were associated with inferior survival of AML-RUNX1<sup>mut</sup>. Allo-HSCT can significantly improve the prognosis of AML-RUNX1<sup>mut</sup>.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139897933","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}
Francesca Romana Mauro, Alessandra Tedeschi, Marzia Varettoni, Francesco Zaja, Giovanni Barosi, Pier Luigi Zinzani
Zanubrutinib has been approved for treating patients with different lymphoproliferative disorders and now represents a significant breakthrough in treating relapsed/refractory and previously untreated patients with chronic lymphocytic leukemia (CLL). Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of zanubrutinib in approved indications may be challenging. This article presents the results of a group discussion among an ad hoc constituted panel of experts to identify and address unmet clinical needs (UCNs) in using zanubrutinib in patients with CLL. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. Panel members reviewed the results of first-line and upstream controlled trials in which the efficacy and toxicity profile of zanubrutinib and other BTK inhibitors were investigated in patients with CLL. Based on a critical discussion of data, the panel produced recommendations for using zanubrutinib and proposals for new studies to increase the evidence for the optimal treatment of patients with CLL. The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners.
{"title":"Identifying and addressing unmet clinical needs on the use of zanubrutinib in chronic lymphocytic leukemia: A consensus-based position paper from an ad hoc expert panel","authors":"Francesca Romana Mauro, Alessandra Tedeschi, Marzia Varettoni, Francesco Zaja, Giovanni Barosi, Pier Luigi Zinzani","doi":"10.1002/hon.3255","DOIUrl":"10.1002/hon.3255","url":null,"abstract":"<p>Zanubrutinib has been approved for treating patients with different lymphoproliferative disorders and now represents a significant breakthrough in treating relapsed/refractory and previously untreated patients with chronic lymphocytic leukemia (CLL). Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of zanubrutinib in approved indications may be challenging. This article presents the results of a group discussion among an ad hoc constituted panel of experts to identify and address unmet clinical needs (UCNs) in using zanubrutinib in patients with CLL. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. Panel members reviewed the results of first-line and upstream controlled trials in which the efficacy and toxicity profile of zanubrutinib and other BTK inhibitors were investigated in patients with CLL. Based on a critical discussion of data, the panel produced recommendations for using zanubrutinib and proposals for new studies to increase the evidence for the optimal treatment of patients with CLL. The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740867","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}
Chronic lymphocytic leukemia (CLL) is the most common leukemia in western societies, recognized by clinical and molecular heterogeneity. Despite the success of targeted therapies, acquired resistance remains a challenge for relapsed and refractory CLL, as a consequence of mutations in the target or the upregulation of other survival pathways leading to the progression of the disease. Research on proteins that can trigger such pathways may define novel therapies for a successful outcome in CLL such as the receptor tyrosine kinase-like orphan receptor 1 (ROR1). ROR1 is a signaling receptor for Wnt5a, with an important role during embryogenesis. The aberrant expression on CLL cells and several types of tumors, is involved in cell proliferation, survival, migration as well as drug resistance. Antibody-based immunotherapies and small-molecule compounds emerged to target ROR1 in preclinical and clinical studies. Efforts have been made to identify new prognostic markers having predictive value to refine and increase the detection and management of CLL. ROR1 can be considered as an attractive target for CLL diagnosis, prognosis, and treatment. It can be clinically effective alone and/or in combination with current approved agents. In this review, we summarize the scientific achievements in targeting ROR1 for CLL diagnosis, prognosis, and treatment.
{"title":"How receptor tyrosine kinase-like orphan receptor 1 meets its partners in chronic lymphocytic leukemia","authors":"Nayla Mouawad, Edoardo Ruggeri, Guido Capasso, Leonardo Martinello, Andrea Visentin, Federica Frezzato, Livio Trentin","doi":"10.1002/hon.3250","DOIUrl":"https://doi.org/10.1002/hon.3250","url":null,"abstract":"<p>Chronic lymphocytic leukemia (CLL) is the most common leukemia in western societies, recognized by clinical and molecular heterogeneity. Despite the success of targeted therapies, acquired resistance remains a challenge for relapsed and refractory CLL, as a consequence of mutations in the target or the upregulation of other survival pathways leading to the progression of the disease. Research on proteins that can trigger such pathways may define novel therapies for a successful outcome in CLL such as the receptor tyrosine kinase-like orphan receptor 1 (ROR1). ROR1 is a signaling receptor for Wnt5a, with an important role during embryogenesis. The aberrant expression on CLL cells and several types of tumors, is involved in cell proliferation, survival, migration as well as drug resistance. Antibody-based immunotherapies and small-molecule compounds emerged to target ROR1 in preclinical and clinical studies. Efforts have been made to identify new prognostic markers having predictive value to refine and increase the detection and management of CLL. ROR1 can be considered as an attractive target for CLL diagnosis, prognosis, and treatment. It can be clinically effective alone and/or in combination with current approved agents. In this review, we summarize the scientific achievements in targeting ROR1 for CLL diagnosis, prognosis, and treatment.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment-related toxicity disparities in adult Hispanic acute lymphoblastic leukemia patients receiving pegaspargase-based regimens: A multicenter electronic health research network study","authors":"Benjamin J. Lee, Shawn P. Griffin","doi":"10.1002/hon.3254","DOIUrl":"https://doi.org/10.1002/hon.3254","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704702","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}
Marijana Virijevic, Nada Kraguljac-Kurtovic, Mirjana Mitrovic, Ljubomir Jakovic, Zoran Bukumuric, Nikola Pantic, Nikica Sabljic, Zlatko Pravdic, Mirjana Cvetkovic, Vesna Knezevic, Tijana Dragovic-Ivancevic, Irena Djunić, Jovan Rajic, Violeta Milosevic, Milena Todorovic-Balint, Ana Vidovic, Nada Suvajdzic-Vukovic
Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNSpos) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNSneg). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNSneg, those with CNSpos had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30 × 109/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (p = 0.047) and high percentage of BM blasts (p = 0.042) as predictors for CNSpos. CNSpos did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population.
{"title":"Incidence, risk factors, and outcome of asymptomatic central nervous system involvement in adult patients with acute myeloid leukemia","authors":"Marijana Virijevic, Nada Kraguljac-Kurtovic, Mirjana Mitrovic, Ljubomir Jakovic, Zoran Bukumuric, Nikola Pantic, Nikica Sabljic, Zlatko Pravdic, Mirjana Cvetkovic, Vesna Knezevic, Tijana Dragovic-Ivancevic, Irena Djunić, Jovan Rajic, Violeta Milosevic, Milena Todorovic-Balint, Ana Vidovic, Nada Suvajdzic-Vukovic","doi":"10.1002/hon.3253","DOIUrl":"10.1002/hon.3253","url":null,"abstract":"<p>Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNS<sup>pos</sup>) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNS<sup>neg</sup>). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNS<sup>neg</sup>, those with CNS<sup>pos</sup> had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30 × 10<sup>9</sup>/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (<i>p</i> = 0.047) and high percentage of BM blasts (<i>p</i> = 0.042) as predictors for CNS<sup>pos</sup>. CNS<sup>pos</sup> did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584607","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}
Sarcopenia is a crucial factor in the physical fitness of elderly individuals. This study investigated the prognostic values of multiple parameters of sarcopenia in association with established prognostic factors in elderly Japanese patients with diffuse large B cell lymphoma (DLBCL). As candidate indicators for sarcopenia, the skeletal muscle index (SMI) (cm2/m2), the psoas muscle index, the erector spinae muscle index, the visceral fat index, the subcutaneous fat index, and the visceral to subcutaneous fat area ratio at the third lumbar level were assessed by computed tomography at their initial diagnosis in 102 patients with DLBCL over 75 years old those were diagnosed and treated in our institute from 2007 to 2020. The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). The median age of patients analyzed was 80 years at diagnosis. The sex-specific cut-offs for the indices adopted two approaches: (i) the historical cut-off values established in the previous study for healthy Japanese individuals (Hamaguchi Y. J Cachexia Sarcopenia Muscle. 2018), and (ii) each sex-specific lowest quartile in our cohort. As the results, SMI evaluated by the historical cut-off and sex-specific lowest quartile was identified as the most influential independent prognostic factor for both OS and PFS among various parameters for sarcopenia. Furthermore, we developed an elderly sarcopenia prognostic index (ESPI). ESPI, which combines SMI evaluated by the historical cut-off and LDH > ULN, demonstrated statistically significant prognostic impacts on OS and PFS. Moreover, compared to the R-IPI, ESPI showed the ability to identify intermediate-risk groups and indicated a trend toward improved predictive accuracy. Our study revealed that SMI is the most appropriate assessment method for evaluating sarcopenia and the critical prognostic factor in OS and PFS of elderly patients with DLBCL.
肌肉疏松症是影响老年人体能的一个关键因素。本研究调查了日本老年弥漫性大 B 细胞淋巴瘤(DLBCL)患者肌肉疏松症的多个参数与既有预后因素的关联。作为 "肌肉疏松症 "的候选指标,我们通过计算机断层扫描评估了 2007 年至 2020 年期间在我院接受诊断和治疗的 102 名 75 岁以上 DLBCL 患者初诊时的骨骼肌指数(SMI)(cm2/m2)、腰肌指数、竖脊肌指数、内脏脂肪指数、皮下脂肪指数以及第三腰椎水平的内脏与皮下脂肪面积比。主要终点是总生存期(OS),次要终点是无进展生存期(PFS)。被分析患者确诊时的中位年龄为 80 岁。各项指标的性别特异性临界值采用了两种方法:(i) 先前研究中为日本健康人确定的历史临界值(Hamaguchi Y. J Cachexia Sarcopenia Muscle. 2018),以及 (ii) 我们队列中每个性别特异性最低四分位数。结果发现,在肌少症的各种参数中,以历史截止值和性别特异性最低四分位数评估的SMI是对OS和PFS最有影响的独立预后因素。此外,我们还开发了老年肌肉疏松症预后指数(ESPI)。ESPI结合了以历史截止值评估的SMI和LDH >ULN,对OS和PFS的预后影响具有统计学意义。此外,与 R-IPI 相比,ESPI 显示出识别中危人群的能力,并有提高预测准确性的趋势。我们的研究表明,SMI 是评估肌肉疏松症最合适的评估方法,也是老年 DLBCL 患者 OS 和 PFS 的关键预后因素。
{"title":"Skeletal muscle index impacts the treatment outcome of elderly patients with diffuse large B cell lymphoma","authors":"Yui Niiyama-Uchibori, Haruya Okamoto, Akihiro Miyashita, Kentaro Mizuhara, Yuka Kanayama-Kawaji, Takahiro Fujino, Taku Tsukamoto, Shinsuke Mizutani, Yuji Shimura, Satoshi Teramukai, Junya Kuroda","doi":"10.1002/hon.3252","DOIUrl":"https://doi.org/10.1002/hon.3252","url":null,"abstract":"<p>Sarcopenia is a crucial factor in the physical fitness of elderly individuals. This study investigated the prognostic values of multiple parameters of sarcopenia in association with established prognostic factors in elderly Japanese patients with diffuse large B cell lymphoma (DLBCL). As candidate indicators for sarcopenia, the skeletal muscle index (SMI) (cm<sup>2</sup>/m<sup>2</sup>), the psoas muscle index, the erector spinae muscle index, the visceral fat index, the subcutaneous fat index, and the visceral to subcutaneous fat area ratio at the third lumbar level were assessed by computed tomography at their initial diagnosis in 102 patients with DLBCL over 75 years old those were diagnosed and treated in our institute from 2007 to 2020. The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). The median age of patients analyzed was 80 years at diagnosis. The sex-specific cut-offs for the indices adopted two approaches: (i) the historical cut-off values established in the previous study for healthy Japanese individuals (Hamaguchi Y. J Cachexia Sarcopenia Muscle. 2018), and (ii) each sex-specific lowest quartile in our cohort. As the results, SMI evaluated by the historical cut-off and sex-specific lowest quartile was identified as the most influential independent prognostic factor for both OS and PFS among various parameters for sarcopenia. Furthermore, we developed an elderly sarcopenia prognostic index (ESPI). ESPI, which combines SMI evaluated by the historical cut-off and LDH > ULN, demonstrated statistically significant prognostic impacts on OS and PFS. Moreover, compared to the R-IPI, ESPI showed the ability to identify intermediate-risk groups and indicated a trend toward improved predictive accuracy. Our study revealed that SMI is the most appropriate assessment method for evaluating sarcopenia and the critical prognostic factor in OS and PFS of elderly patients with DLBCL.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139550240","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}