Enrica Antonia Martino, Francesca Romana Mauro, Gianluigi Reda, Luca Laurenti, Andrea Visentin, Annamaria Frustaci, Ernesto Vigna, Sara Pepe, Gioacchino Catania, Giacomo Loseto, Roberta Murru, Annalisa Chiarenza, Paolo Sportoletti, Maria Ilaria Del Principe, Roberta Laureana, Marta Coscia, Sara Galimberti, Eleonora Ferretti, Antonella Zucchetto, Riccardo Bomben, Jerry Polesel, Alessandra Tedeschi, Davide Rossi, Livio Trentin, Antonino Neri, Fortunato Morabito, Valter Gattei, Massimo Gentile
Although chronic lymphocytic leukemia (CLL) predominantly affects the elderly, limited data exists about the outcomes of over 80-year-old patients, usually underrepresented in clinical trials. We conducted a multicenter study enrolling 79 consecutive CLL patients ≥80 years at the time of frontline therapy, all treated with ibrutinib. Nearly 48% of cases exhibited unmutated IGHV genes, 32% 17p deletion, and 39.2% TP53 mutations; 63.3% displayed a cumulative illness rating scale (CIRS) > 6. The overall response rate on ibrutinib, computed in 74/79 patients (5 patients excluded for early withdrawal), was 89.9%. After a median follow-up of 28.9 months, the median progression-free survival (PFS) and overall survival (OS) were 42.5 and 51.8 months, respectively. CIRS>6 and temporary discontinuation of ibrutinib lasting for 7–30 days were the only parameters associated with a significantly shorter PFS and were both relevant in predicting a shorter PFS compared to patients with CIRS≤6 and therapy discontinuation ≤7 days. The most common grade≥3 adverse events were infections (25.5%), neutropenia (10.1%), and anemia (2.5%). Eighteen patients (22.8%) experienced a cardiovascular event, including grade-2 atrial fibrillation (n = 9; 11%), grade-2 hypertension (n = 5; 6%), heart failure (n = 3; 3%), and acute coronary syndrome (n = 1; 1%). Mild bleeding events were observed in 27 patients (34.2%). Ibrutinib was permanently discontinued in 26 patients due to progressive disease (n = 11, including 5 Richter's syndromes), secondary malignancies (n = 6), infections (n = 3), cardiac failure (n = 3), severe bleeding (n = 2), and sudden death (n = 1). In conclusion, our analyses confirmed the overall effectiveness and favorable safety profile of the ibrutinib-single agent therapeutic approach in CLL patients ≥80 years.
{"title":"Ibrutinib as first line therapy in chronic lymphocytic leukemia patients over 80 years old: A retrospective real-life multicenter Italian cohort","authors":"Enrica Antonia Martino, Francesca Romana Mauro, Gianluigi Reda, Luca Laurenti, Andrea Visentin, Annamaria Frustaci, Ernesto Vigna, Sara Pepe, Gioacchino Catania, Giacomo Loseto, Roberta Murru, Annalisa Chiarenza, Paolo Sportoletti, Maria Ilaria Del Principe, Roberta Laureana, Marta Coscia, Sara Galimberti, Eleonora Ferretti, Antonella Zucchetto, Riccardo Bomben, Jerry Polesel, Alessandra Tedeschi, Davide Rossi, Livio Trentin, Antonino Neri, Fortunato Morabito, Valter Gattei, Massimo Gentile","doi":"10.1002/hon.3249","DOIUrl":"https://doi.org/10.1002/hon.3249","url":null,"abstract":"<p>Although chronic lymphocytic leukemia (CLL) predominantly affects the elderly, limited data exists about the outcomes of over 80-year-old patients, usually underrepresented in clinical trials. We conducted a multicenter study enrolling 79 consecutive CLL patients ≥80 years at the time of frontline therapy, all treated with ibrutinib. Nearly 48% of cases exhibited unmutated <i>IGHV</i> genes, 32% 17p deletion, and 39.2% <i>TP53</i> mutations; 63.3% displayed a cumulative illness rating scale (CIRS) > 6. The overall response rate on ibrutinib, computed in 74/79 patients (5 patients excluded for early withdrawal), was 89.9%. After a median follow-up of 28.9 months, the median progression-free survival (PFS) and overall survival (OS) were 42.5 and 51.8 months, respectively. CIRS>6 and temporary discontinuation of ibrutinib lasting for 7–30 days were the only parameters associated with a significantly shorter PFS and were both relevant in predicting a shorter PFS compared to patients with CIRS≤6 and therapy discontinuation ≤7 days. The most common grade≥3 adverse events were infections (25.5%), neutropenia (10.1%), and anemia (2.5%). Eighteen patients (22.8%) experienced a cardiovascular event, including grade-2 atrial fibrillation (<i>n</i> = 9; 11%), grade-2 hypertension (<i>n</i> = 5; 6%), heart failure (<i>n</i> = 3; 3%), and acute coronary syndrome (<i>n</i> = 1; 1%). Mild bleeding events were observed in 27 patients (34.2%). Ibrutinib was permanently discontinued in 26 patients due to progressive disease (<i>n</i> = 11, including 5 Richter's syndromes), secondary malignancies (<i>n</i> = 6), infections (<i>n</i> = 3), cardiac failure (<i>n</i> = 3), severe bleeding (<i>n</i> = 2), and sudden death (<i>n</i> = 1). In conclusion, our analyses confirmed the overall effectiveness and favorable safety profile of the ibrutinib-single agent therapeutic approach in CLL patients ≥80 years.</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":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139550239","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":"Prognostic value of the second revision of the international staging system (R2-ISS) in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation","authors":"Taku Kikuchi, Nobuhiro Tsukada, Kodai Kunisada, Moe Yogo, Yuki Oda, Kota Sato, Tomomi Takei, Mizuki Ogura, Yu Abe, Kenshi Suzuki, Tadao Ishida","doi":"10.1002/hon.3248","DOIUrl":"https://doi.org/10.1002/hon.3248","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139435084","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}
Zinc finger protein 384 (ZNF384) rearrangement defined a novel subtype of B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of ZNF384 fusion transcript levels represented measurable residual disease remains to be explored. ZNF384 fusions were screened out in 57 adult B-ALL patients at diagnosis by real-time quantitative polymerase chain reaction and their transcript levels were serially monitored during treatment. The reduction of ZNF384 fusion transcript levels at the time of achieving complete remission had no significant impact on survival, whereas its ≥2.5-log reduction were significantly associated with higher relapse free survival (RFS) and overall survival (OS) rates after course 1 consolidation (p = 0.022 and = 0.0083) and course 2 consolidation (p = 0.0025 and = 0.0008). Compared with chemotherapy alone, allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS of patients with <2.5-log reduction after course 1 consolidation (p < 0.0001 and = 0.0002) and course 2 consolidation (p = 0.0003 and = 0.019), whereas exerted no significant effects in patients with ≥2.5-log reduction (all p > 0.05). ZNF384 fusion transcript levels after course 1 and course 2 consolidation strongly predict relapse and survival and may guide whether receiving allo-HSCT in adult B-ALL.
{"title":"ZNF384 fusion transcript levels for measurable residual disease monitoring in adult B-cell acute lymphoblastic leukemia","authors":"Zong-Yan Shi, Xu Wang, Wen-Min Chen, Ling-Di Li, Yue Hao, Jin-Ying Li, Kai Sun, Xiao-Su Zhao, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Ya-Zhen Qin","doi":"10.1002/hon.3251","DOIUrl":"https://doi.org/10.1002/hon.3251","url":null,"abstract":"<p>Zinc finger protein 384 (<i>ZNF384</i>) rearrangement defined a novel subtype of B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of <i>ZNF384</i> fusion transcript levels represented measurable residual disease remains to be explored. <i>ZNF384</i> fusions were screened out in 57 adult B-ALL patients at diagnosis by real-time quantitative polymerase chain reaction and their transcript levels were serially monitored during treatment. The reduction of <i>ZNF384</i> fusion transcript levels at the time of achieving complete remission had no significant impact on survival, whereas its ≥2.5-log reduction were significantly associated with higher relapse free survival (RFS) and overall survival (OS) rates after course 1 consolidation (<i>p</i> = 0.022 and = 0.0083) and course 2 consolidation (<i>p</i> = 0.0025 and = 0.0008). Compared with chemotherapy alone, allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS of patients with <2.5-log reduction after course 1 consolidation (<i>p</i> < 0.0001 and = 0.0002) and course 2 consolidation (<i>p</i> = 0.0003 and = 0.019), whereas exerted no significant effects in patients with ≥2.5-log reduction (all <i>p</i> > 0.05). <i>ZNF384</i> fusion transcript levels after course 1 and course 2 consolidation strongly predict relapse and survival and may guide whether receiving allo-HSCT in adult B-ALL.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139435083","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}
Zofia Gross, Richard Veyrat-Masson, Béatrice Grange, Sarah Huet, Aurélie Verney, Alexandra Traverse-Glehen, Philippe Ruminy, Lucile Baseggio
Flow cytometry (FCM) has become a method of choice for immunologic characterization of chronic lymphoproliferative disease (CLPD). To reduce the potential subjectivities of FCM data interpretation, we developed a machine learning random forest algorithm (RF) allowing unsupervised analysis. This assay relies on 16 parameters obtained from our FCM screening panel, routinely used in the exploration of peripheral blood (PB) samples (mean fluorescence intensity values (MFI) of CD19, CD45, CD5, CD20, CD200, CD23, HLA-DR, CD10 in CD19-gated B cells, ratio of kappa/Lambda, and different ratios of MFI B-cells/T-cells [CD20, CD200, CD23]). The RF algorithm was trained and validated on a large cohort of more than 300 annotated different CLPD cases (chronic B-cell leukemia, mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma, splenic red pulp lymphoma, hairy cell leukemia) and non-tumoral selected from PB samples. The RF algorithm was able to differentiate tumoral from non-tumoral B-cells in all cases and to propose a correct CLPD classification in more than 90% of cases. In conclusion the RF algorithm could be proposed as an interesting help to FCM data interpretation allowing a first B-cells CLPD diagnostic hypothesis and/or to guide the management of complementary analysis (additional immunologic markers and genetic).
流式细胞术(FCM)已成为慢性淋巴细胞增生性疾病(CLPD)免疫学特征描述的首选方法。为了减少 FCM 数据解读的潜在主观性,我们开发了一种机器学习随机森林算法 (RF),允许进行无监督分析。这种检测方法依赖于从我们的 FCM 筛选面板中获得的 16 个参数,这些参数通常用于外周血(PB)样本的检测(CD19、CD45、CD5、CD20、CD200、CD23、HLA-DR、CD19 门控 B 细胞中的 CD10 的平均荧光强度值 (MFI)、kappa/Lambda 比率以及 MFI B 细胞/T 细胞 [CD20、CD200、CD23] 的不同比率)。RF 算法是在一大批 300 多个注释不同的 CLPD 病例(慢性 B 细胞白血病、套细胞淋巴瘤、边缘区淋巴瘤、滤泡淋巴瘤、脾红髓淋巴瘤、毛细胞白血病)和从 PB 样本中筛选出的非肿瘤病例上训练和验证的。射频算法能够区分所有病例中的肿瘤性和非肿瘤性 B 细胞,并对 90% 以上的病例提出了正确的 CLPD 分类。总之,RF 算法可以作为 FCM 数据解读的一个有趣的帮助,允许提出第一个 B 细胞 CLPD 诊断假设和/或指导补充分析(其他免疫标记物和基因)的管理。
{"title":"Diagnosis of chronic B-cell lymphoproliferative disease in peripheral blood = how machine learning may help to the interpretation of flow cytometry data","authors":"Zofia Gross, Richard Veyrat-Masson, Béatrice Grange, Sarah Huet, Aurélie Verney, Alexandra Traverse-Glehen, Philippe Ruminy, Lucile Baseggio","doi":"10.1002/hon.3245","DOIUrl":"https://doi.org/10.1002/hon.3245","url":null,"abstract":"<p>Flow cytometry (FCM) has become a method of choice for immunologic characterization of chronic lymphoproliferative disease (CLPD). To reduce the potential subjectivities of FCM data interpretation, we developed a machine learning random forest algorithm (RF) allowing unsupervised analysis. This assay relies on 16 parameters obtained from our FCM screening panel, routinely used in the exploration of peripheral blood (PB) samples (mean fluorescence intensity values (MFI) of CD19, CD45, CD5, CD20, CD200, CD23, HLA-DR, CD10 in CD19-gated B cells, ratio of kappa/Lambda, and different ratios of MFI B-cells/T-cells [CD20, CD200, CD23]). The RF algorithm was trained and validated on a large cohort of more than 300 annotated different CLPD cases (chronic B-cell leukemia, mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma, splenic red pulp lymphoma, hairy cell leukemia) and non-tumoral selected from PB samples. The RF algorithm was able to differentiate tumoral from non-tumoral B-cells in all cases and to propose a correct CLPD classification in more than 90% of cases. In conclusion the RF algorithm could be proposed as an interesting help to FCM data interpretation allowing a first B-cells CLPD diagnostic hypothesis and/or to guide the management of complementary analysis (additional immunologic markers and genetic).</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139109831","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}
Antonio Pinto, Marco Ladetto, Maurizio Martelli, Carlo Visco, Francesco Zaja, Emanuele Guardalben, Pier Luigi Zinzani
{"title":"Unmet needs in relapsed/refractory mantle cell lymphoma after failure of covalent Bruton's tyrosine kinase inhibitors: An Italian scenario","authors":"Antonio Pinto, Marco Ladetto, Maurizio Martelli, Carlo Visco, Francesco Zaja, Emanuele Guardalben, Pier Luigi Zinzani","doi":"10.1002/hon.3246","DOIUrl":"https://doi.org/10.1002/hon.3246","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139109832","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}
Mycosis fungoides (MF) progresses slowly before advancing to skin tumors followed by lymph node and visceral involvement. Among MF progression, stage IIB is an initial time point of tumor formation in MF. Since MF in tumor stage possess abundant blood vessels, it is important to evaluate the pro-angiogenic factors before and after MF in stage IIB. In this report, we investigated pro-angiogenic soluble factors in MF patients, as well as its pro-angiogenetic effects on tumor cells and stroma cells. We first evaluated the serum levels of pro-angiogenic factors in 9 MF patients without tumor formation and 8 MF patients with tumor formation. Among them, the serum MMP-9 and plasminogen activator inhibitors 1 (PAI-1) was significantly increased in MF with tumor formation compared in MF without tumor formation, leading to favorable formation of human dermal microvascular endothelial cells tube networks. Moreover, PAI-1 stimulation significantly increased the mRNA expression and protein production MMP-9 on monocytes derived M2 macrophages and HUT-78. Furthermore, since MMP-9 production from tumor cells as well as stromal cells is suppressed by bexarotene, we evaluate the baseline serum pro-angiogenic factors including MMP-9 in 16 patients with advanced cutaneous T cell lymphoma treated with bexarotene. The serum levels of MMP-2 and MMP-9 was significantly increased in bexarotene non-responded patients compared to responded patients. Our present study suggested the significance of MMP-9 and PAI-1 for the progression of MF stage toward to the tumor stage, and could be a therapeutic target in future.
{"title":"Possible effects of plasminogen activator inhibitor-1 on promoting angiogenesis through matrix metalloproteinase 9 in advanced mycosis fungoides","authors":"Taku Fujimura, Kentaro Ohuchi, Tetsuya Ikawa, Yumi Kambayashi, Ryo Amagai, Sadanori Furudate, Yoshihide Asano","doi":"10.1002/hon.3244","DOIUrl":"https://doi.org/10.1002/hon.3244","url":null,"abstract":"<p>Mycosis fungoides (MF) progresses slowly before advancing to skin tumors followed by lymph node and visceral involvement. Among MF progression, stage IIB is an initial time point of tumor formation in MF. Since MF in tumor stage possess abundant blood vessels, it is important to evaluate the pro-angiogenic factors before and after MF in stage IIB. In this report, we investigated pro-angiogenic soluble factors in MF patients, as well as its pro-angiogenetic effects on tumor cells and stroma cells. We first evaluated the serum levels of pro-angiogenic factors in 9 MF patients without tumor formation and 8 MF patients with tumor formation. Among them, the serum MMP-9 and plasminogen activator inhibitors 1 (PAI-1) was significantly increased in MF with tumor formation compared in MF without tumor formation, leading to favorable formation of human dermal microvascular endothelial cells tube networks. Moreover, PAI-1 stimulation significantly increased the mRNA expression and protein production MMP-9 on monocytes derived M2 macrophages and HUT-78. Furthermore, since MMP-9 production from tumor cells as well as stromal cells is suppressed by bexarotene, we evaluate the baseline serum pro-angiogenic factors including MMP-9 in 16 patients with advanced cutaneous T cell lymphoma treated with bexarotene. The serum levels of MMP-2 and MMP-9 was significantly increased in bexarotene non-responded patients compared to responded patients. Our present study suggested the significance of MMP-9 and PAI-1 for the progression of MF stage toward to the tumor stage, and could be a therapeutic target in future.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139109833","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}
M. Picardi, C. Giordano, N. Pugliese, M. Mascolo, S. Varricchio, G. Troncone, E. Vigliar, C. Bellavicine, M. Lamagna, D. Lisi, A. Vincenzi, F. Pane
Tumor-infiltrating macrophages (TIMs) are constantly ≥5% staining at immunohistochemical analysis on biopsy specimens of tumor masses, in primary mediastinal large B-cell lymphoma (PMBL) and mediastinal gray zone lymphoma (MGZL).1-3 The presence of many CD68-positive TIMs into lymph node microenvironment of both PMBL and MGZL is associated with shortened progression-free survival (PFS) following conventional anthracycline-based regimens.1-3 Myocet™ is doxorubicin encapsulated in a non-pegylated liposomal membrane of phosphatidylcholine and cholesterol.4 Increased dosages of non-pegylated liposomal-encapsulated doxorubicin (NPLD) may have some pharmacokinetic and pharmacodynamic advantages4, 5 since it rapidly accumulates at high levels within macrophage cells of the microenvironment of malignant lymphadenopathies, acting as slow-release reservoir with prolonged powerful tumoricidal effects specifically inside the neoplastic tissue.6, 7 These effects might be perceived as a great benefit in those patients with aggressive non-Hodgkin lymphoma with high tumor burden. For this reason, a dose intensified (DI) strategy with NPLD was used for untreated advanced-stage diffuse large B-cell lymphoma (DLBCL), instead of hydroxydaunorubicin in rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone (R-CHOP), thus constituting a new regimen, so called R-COMP-DI.8 The scheme resulted to have better activity profile compared to the historical R-CHOP data.8, 9 Furthermore, a personal extrapolation from published data showed very low rate of discontinued treatment due to drug related adverse events following intensified version of R-COMP.8-10 On the basis of these data, in our Institution a frontline approach with increased dosage of Myocet™ has been routinely employed in PMBL and MGZL for the last 6 years. We report a real-life experience on the efficacy and safety of a new scheme named R-COMP-DIx6, with a supercharge dose of NPLD for six cycles every 3 weeks, in patients with newly diagnosed PMBL and MGZL. The R-COMP-DIx6 schedule consisted of 1-day outpatient intravenous infusions of Myocet™ at an escalated dose of 70 mg/m2, plus rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 (up to a maximal dose of 2 mg) and prednisone 40 mg/m2 per day for 5 days, at a 3-week interval for a total of six cycles. The cumulative dose of NPLD was 420 mg/m2 for the entire scheme of 6 cycles giving an increased dose of 70 mg/m2 per each cycle. The dose-intensity of NPLD in cycles one to six of R-COMP-DIx6 was increased to 140% of standard dosage and was well within the ceiling dose of 785 mg/m2 (the median lifetime dose report
{"title":"Liposomal-encapsulated doxorubicin supercharge-containing front-line treatment improves response rates in primary mediastinal large B-cell lymphoma and mediastinal gray zone lymphoma","authors":"M. Picardi, C. Giordano, N. Pugliese, M. Mascolo, S. Varricchio, G. Troncone, E. Vigliar, C. Bellavicine, M. Lamagna, D. Lisi, A. Vincenzi, F. Pane","doi":"10.1002/hon.3242","DOIUrl":"10.1002/hon.3242","url":null,"abstract":"<p>Tumor-infiltrating macrophages (TIMs) are constantly ≥5% staining at immunohistochemical analysis on biopsy specimens of tumor masses, in primary mediastinal large B-cell lymphoma (PMBL) and mediastinal gray zone lymphoma (MGZL).<span><sup>1-3</sup></span> The presence of many CD68-positive TIMs into lymph node microenvironment of both PMBL and MGZL is associated with shortened progression-free survival (PFS) following conventional anthracycline-based regimens.<span><sup>1-3</sup></span> Myocet™ is doxorubicin encapsulated in a non-pegylated liposomal membrane of phosphatidylcholine and cholesterol.<span><sup>4</sup></span> Increased dosages of non-pegylated liposomal-encapsulated doxorubicin (NPLD) may have some pharmacokinetic and pharmacodynamic advantages<span><sup>4, 5</sup></span> since it rapidly accumulates at high levels within macrophage cells of the microenvironment of malignant lymphadenopathies, acting as slow-release reservoir with prolonged powerful tumoricidal effects specifically inside the neoplastic tissue.<span><sup>6, 7</sup></span> These effects might be perceived as a great benefit in those patients with aggressive non-Hodgkin lymphoma with high tumor burden. For this reason, a dose intensified (DI) strategy with NPLD was used for untreated advanced-stage diffuse large B-cell lymphoma (DLBCL), instead of hydroxydaunorubicin in rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone (R-CHOP), thus constituting a new regimen, so called R-COMP-DI.<span><sup>8</sup></span> The scheme resulted to have better activity profile compared to the historical R-CHOP data.<span><sup>8, 9</sup></span> Furthermore, a personal extrapolation from published data showed very low rate of discontinued treatment due to drug related adverse events following intensified version of R-COMP.<span><sup>8-10</sup></span> On the basis of these data, in our Institution a frontline approach with increased dosage of Myocet™ has been routinely employed in PMBL and MGZL for the last 6 years. We report a real-life experience on the efficacy and safety of a new scheme named R-COMP-DI<sup>x6</sup>, with a supercharge dose of NPLD for six cycles every 3 weeks, in patients with newly diagnosed PMBL and MGZL. The R-COMP-DI<sup>x6</sup> schedule consisted of 1-day outpatient intravenous infusions of Myocet™ at an escalated dose of 70 mg/m<sup>2</sup>, plus rituximab 375 mg/m<sup>2</sup>, cyclophosphamide 750 mg/m<sup>2</sup>, vincristine 1.4 mg/m<sup>2</sup> (up to a maximal dose of 2 mg) and prednisone 40 mg/m<sup>2</sup> per day for 5 days, at a 3-week interval for a total of six cycles. The cumulative dose of NPLD was 420 mg/m<sup>2</sup> for the entire scheme of 6 cycles giving an increased dose of 70 mg/m<sup>2</sup> per each cycle. The dose-intensity of NPLD in cycles one to six of R-COMP-DI<sup>x6</sup> was increased to 140% of standard dosage and was well within the ceiling dose of 785 mg/m<sup>2</sup> (the median lifetime dose report","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138823704","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}
Hazim S. Ababneh, Matthew J. Frigault, Andrea K. Ng, Chirayu G. Patel
{"title":"Radiation therapy as bridging and salvage strategy among patients with secondary central nervous system lymphoma undergoing CD19-targeted chimeric antigen receptor T-cell therapy","authors":"Hazim S. Ababneh, Matthew J. Frigault, Andrea K. Ng, Chirayu G. Patel","doi":"10.1002/hon.3243","DOIUrl":"10.1002/hon.3243","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803086","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}
Jakob R. Passweg, Helen Baldomero, Marc Ansari, Caroline Arber, Yves Chalandon, Michael Daskalakis, Miriam Diepold, Tamara Diesch-Furlanetto, Michel A. Duchosal, Sabine Gerull, Tayfun Güngör, Dominik Heim, Felicitas Hitz, Andreas Holbro, Stavroula Masouridi-Levrat, Gayathri Nair, Urban Novak, Thomas Pabst, Christoph Renner, Georg Stussi, Dominik Schneidawind, Urs Schanz, Luciano Wannesson, Jörg P. Halter, for the Swiss Blood Stem Cell Transplantation Group (SBST)
The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997–2001, 2002–2006, 2007–2011, 2012–2016, and 2017–2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33.7 vs. 54.3) and had more frequently unrelated donors and reduced intensity conditioning in later quinquennia. Similarly, age increased for recipients of autologous HCT (median 48.3 vs. 59.9). We did not see a significant drop in transplant activity during the SARS-CoV-2 pandemic. Analysis of outcome showed overall survival (relative risk (RR) of death 0.664 (0.529–0.832) and progression free survival (RR 0.708 (0.577–0.870) being improved over time comparing the latest to the first quinquennium adjusting for risk factors. Non-relapse mortality decreased in recipients of allogeneic HCT (RR: 0.371 (0.270–0.509)) over time but relapse risks did not. Outcome of autologous HCT improved as well across quinquennia, this improvement was mainly due to decreased relapse risks (RR 0.681 (0.597–0.777)), possibly related to maintenance treatment or rescue treatment for relapse mainly in myeloma patients. Cellular therapies other than allogeneic or autologous HCT, particularly chimeric antigen receptor T-cells (CAR-T) treatment have started to increase after 2019, year of approval of the first commercial CAR-T product in Switzerland. Data on chimeric antigen receptor T-cell treatment are too early for comparative analyses. Detailed analyses of changes over time are presented. This study includes all HCTs, and cellular therapies, data useful for quality assurance programs, health care cost estimation and benchmarking. Between 50% and 60% of patients are long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care.
瑞士血液干细胞移植和细胞治疗小组(SBST)领导所有造血干细胞移植(HCT)和细胞治疗的强制性国家注册。25年后,11226名接受HCT的患者(4031名异体和7195名自体)的信息可获得,其中包括925名儿科患者。我们比较了1997-2001年、2002-2006年、2007-2011年、2012-2016年和2017-2021年5年期患者的特征和结果。随着时间的推移,有许多变化。同种异体移植受者年龄变大(中位年龄33.7岁vs. 54.3岁),非亲属供者增多,5岁后期强度调节降低。同样,自体HCT受者的年龄增加(中位48.3 vs. 59.9)。在SARS-CoV-2大流行期间,我们没有看到移植活动显著下降。结果分析显示,经危险因素调整后,与第一个五年期比较,总生存期(死亡相对风险(RR)为0.664(0.529-0.832),无进展生存期(RR 0.708(0.577-0.870))随着时间的推移而改善。同种异体HCT接受者的非复发死亡率随着时间的推移而下降(RR: 0.371(0.270-0.509)),但复发风险没有下降。自体HCT的预后在5年期间也有改善,这种改善主要是由于复发风险降低(RR 0.681(0.597-0.777)),可能与主要针对骨髓瘤患者复发的维持治疗或抢救治疗有关。继2019年瑞士首个商业化CAR-T产品获批后,同种异体或自体HCT以外的细胞疗法,特别是嵌合抗原受体t细胞(CAR-T)治疗开始增加。关于嵌合抗原受体t细胞治疗的数据还为时过早,无法进行比较分析。详细分析了随着时间的变化。本研究包括所有hct、细胞疗法、质量保证项目、卫生保健成本估算和基准测试的有用数据。在两种类型的HCT后,50%至60%的患者是长期幸存者,这表明需要长期护理的存活患者人数不断增加。
{"title":"Hematopoietic cell transplantation and cellular therapies in Switzerland. Evolution over 25 years. A report from the stem cell transplantation and cellular therapies working groups of the SBST 1997–2021","authors":"Jakob R. Passweg, Helen Baldomero, Marc Ansari, Caroline Arber, Yves Chalandon, Michael Daskalakis, Miriam Diepold, Tamara Diesch-Furlanetto, Michel A. Duchosal, Sabine Gerull, Tayfun Güngör, Dominik Heim, Felicitas Hitz, Andreas Holbro, Stavroula Masouridi-Levrat, Gayathri Nair, Urban Novak, Thomas Pabst, Christoph Renner, Georg Stussi, Dominik Schneidawind, Urs Schanz, Luciano Wannesson, Jörg P. Halter, for the Swiss Blood Stem Cell Transplantation Group (SBST)","doi":"10.1002/hon.3241","DOIUrl":"10.1002/hon.3241","url":null,"abstract":"<p>The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997–2001, 2002–2006, 2007–2011, 2012–2016, and 2017–2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33.7 vs. 54.3) and had more frequently unrelated donors and reduced intensity conditioning in later quinquennia. Similarly, age increased for recipients of autologous HCT (median 48.3 vs. 59.9). We did not see a significant drop in transplant activity during the SARS-CoV-2 pandemic. Analysis of outcome showed overall survival (relative risk (RR) of death 0.664 (0.529–0.832) and progression free survival (RR 0.708 (0.577–0.870) being improved over time comparing the latest to the first quinquennium adjusting for risk factors. Non-relapse mortality decreased in recipients of allogeneic HCT (RR: 0.371 (0.270–0.509)) over time but relapse risks did not. Outcome of autologous HCT improved as well across quinquennia, this improvement was mainly due to decreased relapse risks (RR 0.681 (0.597–0.777)), possibly related to maintenance treatment or rescue treatment for relapse mainly in myeloma patients. Cellular therapies other than allogeneic or autologous HCT, particularly chimeric antigen receptor T-cells (CAR-T) treatment have started to increase after 2019, year of approval of the first commercial CAR-T product in Switzerland. Data on chimeric antigen receptor T-cell treatment are too early for comparative analyses. Detailed analyses of changes over time are presented. This study includes all HCTs, and cellular therapies, data useful for quality assurance programs, health care cost estimation and benchmarking. Between 50% and 60% of patients are long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498186","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}
Pellegrino Musto, Jon Salmanton-García, Nicola Sgherza, Rui Bergantim, Francesca Farina, Andreas Glenthøj, Guldane Cengiz Seval, Barbora Weinbergerová, Valentina Bonuomo, Yavuz M. Bilgin, Jaap van Doesum, Ozren Jaksic, Benjamín Víšek, Iker Falces-Romero, Monia Marchetti, Julio Dávila-Valls, Sonia Martín-Pérez, Marcio Nucci, Alberto López-García, Federico Itri, Caterina Buquicchio, Luisa Verga, Klára Piukovics, Milan Navrátil, Graham P. Collins, Moraima Jiménez, Nicola S. Fracchiolla, Jorge Labrador, Lucia Prezioso, Elena Rossi, Natasha Čolović, Stef Meers, Austin Kulasekararaj, Annarosa Cuccaro, Ola Blennow, Toni Valković, Uluhan Sili, Marie-Pierre Ledoux, Josip Batinić, Francesco Passamonti, Marina Machado, Rafael F. Duarte, Christian Bjørn Poulsen, Gustavo-Adolfo Méndez, Ildefonso Espigado, Fatih Demirkan, Martin Čerňan, Chiara Cattaneo, Verena Petzer, Gabriele Magliano, Carolina Garcia-Vidal, Shaimaa El-Ashwah, Maria Gomes-Da-Silva, Antonio Vena, Irati Ormazabal-Vélez, Jens van Praet, Michelina Dargenio, Cristina De-Ramón, Maria Ilaria Del Principe, Joyce Marques-De-Almeida, Dominik Wolf, Tomáš Szotkowski, Aleš Obr, Gökçe Melis Çolak, Anna Nordlander, Macarena Izuzquiza, Alba Cabirta, Giovanni Paolo Maria Zambrotta, Raul Cordoba, Pavel Žák, Emanuele Ammatuna, Jiří Mayer, Osman Ilhan, Ramón García-Sanz, Martina Quattrone, Elena Arellano, Raquel Nunes-Rodrigues, Ziad Emarah, Tommaso Francesco Aiello, Michaela Hanakova, Zdeněk Ráčil, Martina Bavastro, Alessandro Limongelli, Laman Rahimli, Francesco Marchesi, Oliver A. Cornely, Livio Pagano
Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109/L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.
{"title":"Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry","authors":"Pellegrino Musto, Jon Salmanton-García, Nicola Sgherza, Rui Bergantim, Francesca Farina, Andreas Glenthøj, Guldane Cengiz Seval, Barbora Weinbergerová, Valentina Bonuomo, Yavuz M. Bilgin, Jaap van Doesum, Ozren Jaksic, Benjamín Víšek, Iker Falces-Romero, Monia Marchetti, Julio Dávila-Valls, Sonia Martín-Pérez, Marcio Nucci, Alberto López-García, Federico Itri, Caterina Buquicchio, Luisa Verga, Klára Piukovics, Milan Navrátil, Graham P. Collins, Moraima Jiménez, Nicola S. Fracchiolla, Jorge Labrador, Lucia Prezioso, Elena Rossi, Natasha Čolović, Stef Meers, Austin Kulasekararaj, Annarosa Cuccaro, Ola Blennow, Toni Valković, Uluhan Sili, Marie-Pierre Ledoux, Josip Batinić, Francesco Passamonti, Marina Machado, Rafael F. Duarte, Christian Bjørn Poulsen, Gustavo-Adolfo Méndez, Ildefonso Espigado, Fatih Demirkan, Martin Čerňan, Chiara Cattaneo, Verena Petzer, Gabriele Magliano, Carolina Garcia-Vidal, Shaimaa El-Ashwah, Maria Gomes-Da-Silva, Antonio Vena, Irati Ormazabal-Vélez, Jens van Praet, Michelina Dargenio, Cristina De-Ramón, Maria Ilaria Del Principe, Joyce Marques-De-Almeida, Dominik Wolf, Tomáš Szotkowski, Aleš Obr, Gökçe Melis Çolak, Anna Nordlander, Macarena Izuzquiza, Alba Cabirta, Giovanni Paolo Maria Zambrotta, Raul Cordoba, Pavel Žák, Emanuele Ammatuna, Jiří Mayer, Osman Ilhan, Ramón García-Sanz, Martina Quattrone, Elena Arellano, Raquel Nunes-Rodrigues, Ziad Emarah, Tommaso Francesco Aiello, Michaela Hanakova, Zdeněk Ráčil, Martina Bavastro, Alessandro Limongelli, Laman Rahimli, Francesco Marchesi, Oliver A. Cornely, Livio Pagano","doi":"10.1002/hon.3240","DOIUrl":"10.1002/hon.3240","url":null,"abstract":"<p>Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 10<sup>9</sup>/L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482322","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}