Pub Date : 2024-09-05DOI: 10.1080/10428194.2024.2400217
Sean Harrop, Michael Dickinson
{"title":"Eligibility for clinical trials in diffuse large B-cell lymphoma: are we sweating the small stuff?","authors":"Sean Harrop, Michael Dickinson","doi":"10.1080/10428194.2024.2400217","DOIUrl":"https://doi.org/10.1080/10428194.2024.2400217","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133152","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 : 2024-09-05DOI: 10.1080/10428194.2024.2400228
Zhao Yin, Ya Gao, Xiaoyin Bu, Junhui Wang, Zurong Yao, Qifa Liu, Yu Zhang, Guopan Yu, Baohong Ping
Venetoclax (VEN), a B-cell lymphoma 2 (BCL-2) selective inhibitor, is widely used for treating acute myeloid leukemia (AML) with promising results. However, the anti-leukemic effect of VEN in relapsed/refractory (R/R)- AML requires improvement. In this study, we observed that combining homoharringtonine (HHT) with VEN plus azacitidine resulted in a significantly higher response and better survival than VA alone in patients with R/R-AML. Basic research indicates that HHT combined with VEN has a highly synergistic effect against both resistant AML cells and primary cells with/without mesenchymal stem cell (MSC) co-culture in vivo, inhibiting proliferation and colony-forming capacity of AML cells associated with concomitant cell cycle arrest. Mechanistically, HHT sensitizes AML cells to VEN by downregulating the anti-apoptotic proteins MCL-1/BCL-xL, activating reactive oxygen species (ROS), leading to mitochondrial membrane potential loss, and attenuating fatty acid (FA) uptake. These findings adding HHT to VEN-based regimens may enhance outcomes in R/R-AML patients.
Venetoclax(VEN)是一种B细胞淋巴瘤2(BCL-2)选择性抑制剂,被广泛用于治疗急性髓性白血病(AML),并取得了良好的疗效。然而,VEN在复发/难治性(R/R)AML中的抗白血病效果有待改善。在这项研究中,我们观察到,在复发性/难治性急性髓细胞白血病(R/R-AML)患者中,将同型半胱氨酸(HHT)与 VEN 加上阿扎胞苷联合使用,比单独使用 VA 的反应明显更强,生存率更高。基础研究表明,HHT 联合 VEN 对体内耐药急性髓细胞白血病细胞和间充质干细胞(MSC)共培养/不共培养的原代细胞均有高度协同作用,可抑制急性髓细胞白血病细胞的增殖和集落形成能力,同时抑制细胞周期停滞。从机理上讲,HHT通过下调抗凋亡蛋白MCL-1/BCL-xL、激活活性氧(ROS)导致线粒体膜电位丧失和减少脂肪酸(FA)摄取,使AML细胞对VEN敏感。这些研究结果表明,在基于 VEN 的治疗方案中加入 HHT 可提高 R/R-AML 患者的治疗效果。
{"title":"Homoharringtonine sensitized resistant acute myeloid leukemia cells to venetoclax-induced apoptosis.","authors":"Zhao Yin, Ya Gao, Xiaoyin Bu, Junhui Wang, Zurong Yao, Qifa Liu, Yu Zhang, Guopan Yu, Baohong Ping","doi":"10.1080/10428194.2024.2400228","DOIUrl":"https://doi.org/10.1080/10428194.2024.2400228","url":null,"abstract":"<p><p>Venetoclax (VEN), a B-cell lymphoma 2 (BCL-2) selective inhibitor, is widely used for treating acute myeloid leukemia (AML) with promising results. However, the anti-leukemic effect of VEN in relapsed/refractory (R/R)- AML requires improvement. In this study, we observed that combining homoharringtonine (HHT) with VEN plus azacitidine resulted in a significantly higher response and better survival than VA alone in patients with R/R-AML. Basic research indicates that HHT combined with VEN has a highly synergistic effect against both resistant AML cells and primary cells with/without mesenchymal stem cell (MSC) co-culture <i>in vivo</i>, inhibiting proliferation and colony-forming capacity of AML cells associated with concomitant cell cycle arrest. Mechanistically, HHT sensitizes AML cells to VEN by downregulating the anti-apoptotic proteins MCL-1/BCL-xL, activating reactive oxygen species (ROS), leading to mitochondrial membrane potential loss, and attenuating fatty acid (FA) uptake. These findings adding HHT to VEN-based regimens may enhance outcomes in R/R-AML patients.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133153","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 : 2024-09-05DOI: 10.1080/10428194.2024.2393753
Claire M Lanier, Niema B Razavian, Sydney Smith, Ralph B D'Agostino, Ryan T Hughes
The ideal treatment paradigm for bulky diffuse large B-cell lymphoma (DLBCL) remains uncertain. We investigated the impact of tumor bulk in patients treated with systemic therapy alone through Alliance/CALGB 50303. Data from this trial were obtained from the National Cancer Institute's NCTN/NCORP Data Archive. The study assessed the size of nodal sites and estimated progression-free survival (PFS) using Cox proportional hazards models. Stratified analysis factored in International Prognostic Index (IPI) risk scores. Out of 524 patients, 155 had pretreatment scans. Using a 7.5 cm cutoff, 44% were classified as bulky. Bulk did not significantly impact progression-free survival (PFS), whether measured continuously or at thresholds of >5 or >7.5 cm (p = 0.10-p = 0.99). Stratified analyses by treatment group and IPI risk group were also non-significant. In this secondary analysis, a significant association between bulk and PFS was not identified.
对于体积巨大的弥漫大 B 细胞淋巴瘤(DLBCL),理想的治疗模式仍不确定。我们通过Alliance/CALGB 50303研究了肿瘤体积对仅接受全身治疗的患者的影响。该试验的数据来自美国国立癌症研究所(National Cancer Institute)的NCTN/NCORP数据档案。该研究评估了结节部位的大小,并使用 Cox 比例危险模型估算了无进展生存期(PFS)。分层分析考虑了国际预后指数(IPI)风险评分。在 524 例患者中,155 例接受了治疗前扫描。以7.5厘米为界限,44%的患者被归类为体积过大。无论是连续测量,还是以>5或>7.5厘米为临界值测量,肿块对无进展生存期(PFS)的影响都不大(p = 0.10-p = 0.99)。按治疗组和 IPI 风险组进行的分层分析也不显著。在这项二次分析中,未发现体积与 PFS 之间存在显著关联。
{"title":"The impact of initial tumor bulk in DLBCL treated with DA-EPOCH-R <i>vs.</i> R-CHOP: a secondary analysis of alliance/CALGB 50303.","authors":"Claire M Lanier, Niema B Razavian, Sydney Smith, Ralph B D'Agostino, Ryan T Hughes","doi":"10.1080/10428194.2024.2393753","DOIUrl":"https://doi.org/10.1080/10428194.2024.2393753","url":null,"abstract":"<p><p>The ideal treatment paradigm for bulky diffuse large B-cell lymphoma (DLBCL) remains uncertain. We investigated the impact of tumor bulk in patients treated with systemic therapy alone through Alliance/CALGB 50303. Data from this trial were obtained from the National Cancer Institute's NCTN/NCORP Data Archive. The study assessed the size of nodal sites and estimated progression-free survival (PFS) using Cox proportional hazards models. Stratified analysis factored in International Prognostic Index (IPI) risk scores. Out of 524 patients, 155 had pretreatment scans. Using a 7.5 cm cutoff, 44% were classified as bulky. Bulk did not significantly impact progression-free survival (PFS), whether measured continuously or at thresholds of >5 or >7.5 cm (<i>p</i> = 0.10-<i>p</i> = 0.99). Stratified analyses by treatment group and IPI risk group were also non-significant. In this secondary analysis, a significant association between bulk and PFS was not identified.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133154","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 : 2024-09-04DOI: 10.1080/10428194.2024.2398659
Sally Hunter, Georgina Ryland, Jia-Min Pang, Slavisa Ninkovic, Karen Dun, John F Seymour, Piers Blombery
{"title":"Chronic lymphocytic leukemia with <i>MDM2</i> amplification as an alternative pathway to TP53 dysfunction.","authors":"Sally Hunter, Georgina Ryland, Jia-Min Pang, Slavisa Ninkovic, Karen Dun, John F Seymour, Piers Blombery","doi":"10.1080/10428194.2024.2398659","DOIUrl":"https://doi.org/10.1080/10428194.2024.2398659","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126119","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 : 2024-09-04DOI: 10.1080/10428194.2024.2397570
Kellen B Gil, Diana Abbott, Maria L Amaya, Marc Schwartz, Jonathan A Gutman, Andrew Kent, Grace Bosma, Daniel A Pollyea, Christine M McMahon
{"title":"Response to intensive induction chemotherapy after failure of frontline azacitidine and venetoclax in acute myeloid leukemia.","authors":"Kellen B Gil, Diana Abbott, Maria L Amaya, Marc Schwartz, Jonathan A Gutman, Andrew Kent, Grace Bosma, Daniel A Pollyea, Christine M McMahon","doi":"10.1080/10428194.2024.2397570","DOIUrl":"https://doi.org/10.1080/10428194.2024.2397570","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126121","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 : 2024-09-03DOI: 10.1080/10428194.2024.2397072
Adam Phillip Gordon Braun, Alex Herrera
As the integration of novel agents in the frontline therapy has primarily impacted upfront therapy of advanced stage classic Hodgkin lymphoma (cHL), this review will outline current management of advanced stage cHL at first line and at progression and relapse, focusing on the biology, clinical features, and therapeutic approaches. Due to S1826, HD21, and ECHELON-1, the first-line treatment of advanced cHL has dramatically changed, with novel agents part of standard frontline therapy. BV-AVD, BrECADD, and Nivo-AVD are now standard first-line regimens for patients with stage III-IV cHL, with improved outcomes compared to historical data in cHL. The addition of BV and PD-1 inhibitors to relapsed/refractory (r/r) cHL chemotherapy regimens improved outcomes in this population. Now, there is a paradigm shift with PD-1 moving into frontline therapy, so new studies to evaluate the role of these novel agents in salvage will be required to determine the optimal salvage approach in r/r cHL.
{"title":"Advanced stage classic Hodgkin lymphoma (cHL): biology, clinical features, therapeutic approach, and management at relapse.","authors":"Adam Phillip Gordon Braun, Alex Herrera","doi":"10.1080/10428194.2024.2397072","DOIUrl":"https://doi.org/10.1080/10428194.2024.2397072","url":null,"abstract":"<p><p>As the integration of novel agents in the frontline therapy has primarily impacted upfront therapy of advanced stage classic Hodgkin lymphoma (cHL), this review will outline current management of advanced stage cHL at first line and at progression and relapse, focusing on the biology, clinical features, and therapeutic approaches. Due to S1826, HD21, and ECHELON-1, the first-line treatment of advanced cHL has dramatically changed, with novel agents part of standard frontline therapy. BV-AVD, BrECADD, and Nivo-AVD are now standard first-line regimens for patients with stage III-IV cHL, with improved outcomes compared to historical data in cHL. The addition of BV and PD-1 inhibitors to relapsed/refractory (r/r) cHL chemotherapy regimens improved outcomes in this population. Now, there is a paradigm shift with PD-1 moving into frontline therapy, so new studies to evaluate the role of these novel agents in salvage will be required to determine the optimal salvage approach in r/r cHL.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126118","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 : 2024-09-03DOI: 10.1080/10428194.2024.2390561
Mikkel Runason Simonsen, Laura Mors Haunstrup, Freja Tang Severinsen, Rasmus Kuhr Jensen, Peter de Nully Brown, Matthew J Maurer, Arushi Khurana, Paw Jensen, Judit Mészáros Jørgensen, Thomas Stauffer Larsen, Michael Roost Clausen, Christian Bjørn Poulsen, Andriette Dessau-Arp, Tarec Christoffer El-Galaly, Lasse Hjort Jakobsen
Up to 50% of diffuse large B-cell lymphoma (DLBCL) patients are ineligible for participation in clinical trials. Ineligible patients have inferior outcomes, but less is known about the impact of commonly used organ-function-based inclusion criteria on drug efficacy estimates. Data on DLBCL patients treated with CHOP+/-rituximab were retrieved from the Danish Lymphoma Registry. Trial inclusion criteria were extracted from four international DLBCL trials (REMoDL-B, GOYA, POLARIX, and HOVON-84). Differences in overall survival (OS) and 5-year restricted mean survival differences (5 y-RMSDs) between trial eligible and ineligible patients were computed. The effectiveness of adding rituximab to CHOP was quantified by the 5 y-RMSD between CHOP and R-CHOP-treated patients and the impact of individual trial criteria on estimated effectiveness was quantified by Shapley-values. In total, 4,083 R-CHOP-treated and 890 CHOP-treated DLBCL patients were included. Across the trials, 18.6-29.3% of the included R-CHOP-treated patients were deemed ineligible for trial based on organ function and performance status alone. Ineligible patients had significantly worse survival, with adjusted absolute differences in 5-year OS of 9-15%. The impact of individual criteria on the estimated effectiveness of adding rituximab to CHOP was small (Shapley-value range, -2.74-0.31). Using a smaller set of criteria derived from a data-driven approach, the number of eligible patients increased by 16-38% and the 5 y-RMSD increased by 0.7-3.1 months. In conclusion, OS among trial ineligible DLBCL patients is inferior as expected, but relaxing trial criteria would have increased the number of trial participants without making major changes in estimated efficacy for a hypothetical CHOP versus R-CHOP trial. This does not necessarily imply that trial findings based on selected patients are unreliable, as the estimated effectiveness of adding rituximab to CHOP was only slightly affected by omitting selected inclusion criteria.
{"title":"The impact of trial inclusion criteria on outcomes in DLBCL patients treated with R-CHOP in the first line: a Danish nationwide study.","authors":"Mikkel Runason Simonsen, Laura Mors Haunstrup, Freja Tang Severinsen, Rasmus Kuhr Jensen, Peter de Nully Brown, Matthew J Maurer, Arushi Khurana, Paw Jensen, Judit Mészáros Jørgensen, Thomas Stauffer Larsen, Michael Roost Clausen, Christian Bjørn Poulsen, Andriette Dessau-Arp, Tarec Christoffer El-Galaly, Lasse Hjort Jakobsen","doi":"10.1080/10428194.2024.2390561","DOIUrl":"https://doi.org/10.1080/10428194.2024.2390561","url":null,"abstract":"<p><p>Up to 50% of diffuse large B-cell lymphoma (DLBCL) patients are ineligible for participation in clinical trials. Ineligible patients have inferior outcomes, but less is known about the impact of commonly used organ-function-based inclusion criteria on drug efficacy estimates. Data on DLBCL patients treated with CHOP+/-rituximab were retrieved from the Danish Lymphoma Registry. Trial inclusion criteria were extracted from four international DLBCL trials (REMoDL-B, GOYA, POLARIX, and HOVON-84). Differences in overall survival (OS) and 5-year restricted mean survival differences (5 y-RMSDs) between trial eligible and ineligible patients were computed. The effectiveness of adding rituximab to CHOP was quantified by the 5 y-RMSD between CHOP and R-CHOP-treated patients and the impact of individual trial criteria on estimated effectiveness was quantified by Shapley-values. In total, 4,083 R-CHOP-treated and 890 CHOP-treated DLBCL patients were included. Across the trials, 18.6-29.3% of the included R-CHOP-treated patients were deemed ineligible for trial based on organ function and performance status alone. Ineligible patients had significantly worse survival, with adjusted absolute differences in 5-year OS of 9-15%. The impact of individual criteria on the estimated effectiveness of adding rituximab to CHOP was small (Shapley-value range, -2.74-0.31). Using a smaller set of criteria derived from a data-driven approach, the number of eligible patients increased by 16-38% and the 5 y-RMSD increased by 0.7-3.1 months. In conclusion, OS among trial ineligible DLBCL patients is inferior as expected, but relaxing trial criteria would have increased the number of trial participants without making major changes in estimated efficacy for a hypothetical CHOP versus R-CHOP trial. This does not necessarily imply that trial findings based on selected patients are unreliable, as the estimated effectiveness of adding rituximab to CHOP was only slightly affected by omitting selected inclusion criteria.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120194","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}
{"title":"Analysis of the clinical features and outcomes of relapsed intravascular large B-cell lymphoma: a single center study.","authors":"Kentaro Narita, Akinao Okamoto, Sachiko Iba, Rikako Tabata, Daisuke Ikeda, Mitsuaki Oura, Atsushi Uehara, Masami Takeuchi, Kengo Takeuchi, Akihiro Tomita, Kosei Matsue","doi":"10.1080/10428194.2024.2389213","DOIUrl":"https://doi.org/10.1080/10428194.2024.2389213","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120191","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 : 2024-09-03DOI: 10.1080/10428194.2024.2396048
Alessandro Broccoli, Gloria Margiotta-Casaluci, Chiara Pagani, Sara Steffanoni, Simonetta Viviani, Pier Luigi Zinzani, Guido Gini
{"title":"Routine follow-up practices in patients with lymphoma: a nationwide survey by the Italian lymphoma foundation.","authors":"Alessandro Broccoli, Gloria Margiotta-Casaluci, Chiara Pagani, Sara Steffanoni, Simonetta Viviani, Pier Luigi Zinzani, Guido Gini","doi":"10.1080/10428194.2024.2396048","DOIUrl":"https://doi.org/10.1080/10428194.2024.2396048","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120193","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 : 2024-09-03DOI: 10.1080/10428194.2024.2393260
Tinatin Muradashvili, Yuxin Liu, Jennifer VanOudenhove, Sean X Gu, Diane S Krause, Francesca Montanari, Maximillian J Carlino, Rubia Mancuso, Jessica M Stempel, Stephanie Halene, Amer M Zeidan, Nikolai A Podoltsev, Natalia Neparidze
We investigated immune cytopenia in multiple myeloma (MM) patients with concurrent acquired aplastic anemia (AA), focusing on three clinical cases treated with plasma cell-directed therapy. All three patients achieved partial response in MM and one patient experienced complete resolution of AA. Two patients had partial improvement in transfusion requirement but continued to suffer from severe AA, leading to immunosuppressive therapy (IST) with improvement of transfusion requirement in both patients. In vitro serum testing of these patients demonstrated platelet mitochondrial dysfunction and platelet apoptosis but did not show sera-specific inhibition of erythroid colony formation in progenitor cells. The levels of IL8 and IL15 were elevated in MM patients with AA, implicating their potential roles in this co-occurrence. Response to IST points to the possibility of myeloma-dysregulated immune system leading to autoreactive T-cell destruction of hematopoietic stem and progenitor cells, offering insights for developing new treatment for cytopenia in MM.
我们研究了并发获得性再生障碍性贫血(AA)的多发性骨髓瘤(MM)患者的免疫细胞减少症,重点研究了接受血浆细胞导向疗法治疗的三个临床病例。三位患者的骨髓瘤均获得部分应答,其中一位患者的再生障碍性贫血完全缓解。两名患者的输血需求得到部分改善,但仍患有严重的再生障碍性贫血,因此接受了免疫抑制疗法(IST),这两名患者的输血需求都得到了改善。这些患者的体外血清检测显示血小板线粒体功能障碍和血小板凋亡,但未显示血清特异性抑制祖细胞中红细胞集落的形成。在患有 AA 的 MM 患者中,IL8 和 IL15 的水平升高,这表明它们在这种并发症中的潜在作用。对 IST 的反应表明,骨髓瘤失调的免疫系统可能导致自身反应性 T 细胞破坏造血干细胞和祖细胞,这为开发治疗 MM 细胞减少症的新疗法提供了启示。
{"title":"Aplastic anemia in association with multiple myeloma: clinical and pathophysiological insights.","authors":"Tinatin Muradashvili, Yuxin Liu, Jennifer VanOudenhove, Sean X Gu, Diane S Krause, Francesca Montanari, Maximillian J Carlino, Rubia Mancuso, Jessica M Stempel, Stephanie Halene, Amer M Zeidan, Nikolai A Podoltsev, Natalia Neparidze","doi":"10.1080/10428194.2024.2393260","DOIUrl":"https://doi.org/10.1080/10428194.2024.2393260","url":null,"abstract":"<p><p>We investigated immune cytopenia in multiple myeloma (MM) patients with concurrent acquired aplastic anemia (AA), focusing on three clinical cases treated with plasma cell-directed therapy. All three patients achieved partial response in MM and one patient experienced complete resolution of AA. Two patients had partial improvement in transfusion requirement but continued to suffer from severe AA, leading to immunosuppressive therapy (IST) with improvement of transfusion requirement in both patients. <i>In vitro</i> serum testing of these patients demonstrated platelet mitochondrial dysfunction and platelet apoptosis but did not show sera-specific inhibition of erythroid colony formation in progenitor cells. The levels of IL8 and IL15 were elevated in MM patients with AA, implicating their potential roles in this co-occurrence. Response to IST points to the possibility of myeloma-dysregulated immune system leading to autoreactive T-cell destruction of hematopoietic stem and progenitor cells, offering insights for developing new treatment for cytopenia in MM.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120192","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}