首页 > 最新文献

Current Research in Translational Medicine最新文献

英文 中文
Real-world treatment and long-term outcomes after autologous stem cell transplantation in first line for myeloma in France and Algeria before the daratumumab era. 在达拉单抗时代之前,自体干细胞移植在法国和阿尔及利亚一线治疗骨髓瘤后的现实世界治疗和长期结果。
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-29 DOI: 10.1016/j.retram.2026.103566
Emilie Martin, Stéphane Morisset, Mohamad Sobh, Alfred Quillon, Hélène Boyer, Philippe Rey, Emmanuelle Nicolas Virelizier, Souad Assaad, Amine Belhabri, Yann Guillermin, Laure Lebras, Valérie Mialou, Jean-Paul Bourgeot, Mélinda Teyssier, Mohamed Brahimi, Soufi Osmani, Kamila Amani, Samira Bouchama, Lila Charef, Nabil Yafour, Badra Entasoltan, Anne Sophie Michallet, Mohamed-Amine Bekadja, Mauricette Michallet

Introduction: Despite numerous therapeutic advances, first line standard care for eligible multiple myeloma (MM) patients still include high-dose melphalan and autologous stem cell transplantation (ASCT).

Methods: Our study concerned MM patients who received ASCT followed or not by consolidation and maintenance, treated in two reference centers in France (Lyon n=342) and in Algeria (Oran n=452) before the daratumumab era.

Results: Despite differences in resources, we showed similar long-term Overall Survival (OS) for the two groups and similar survival for patients who did not receive any chemotherapy after ASCT for relapse. After using the instant ratio, we found a longer Time to Next Treatment for Algerian patients compared to French patients. Regarding patients who relapsed after ASCT we found a significantly better OS for French patients who received up to 3 lines of treatment after ASCT compared to Algerian patients CONCLUSION: The study of long-term overall survival of MM patients after ASCT remains very useful particularly for countries for which innovative therapies including immunotherapy are not accessible, and the differences observed during ASCT management and after relapse could point to paths for improving certain clinical situations regarding the offer of MM care in these countries.

尽管有许多治疗进展,符合条件的多发性骨髓瘤(MM)患者的一线标准治疗仍然包括大剂量美法兰和自体干细胞移植(ASCT)。方法:我们的研究涉及在daratumumab时代之前,在法国(Lyon n=342)和阿尔及利亚(Oran n=452)两个参考中心接受ASCT治疗或不接受巩固和维持治疗的MM患者。结果:尽管资源存在差异,但我们发现两组患者的长期总生存期(OS)相似,ASCT后复发未接受任何化疗的患者的生存期相似。在使用即时比率后,我们发现阿尔及利亚患者比法国患者的下一次治疗时间更长。对于ASCT后复发的患者,我们发现与阿尔及利亚患者相比,接受ASCT后最多3线治疗的法国患者的OS明显更好。对MM患者在ASCT后的长期总体生存的研究仍然非常有用,特别是对于那些无法获得包括免疫治疗在内的创新疗法的国家,ASCT治疗期间和复发后观察到的差异可以为改善这些国家MM护理的某些临床情况指明道路。
{"title":"Real-world treatment and long-term outcomes after autologous stem cell transplantation in first line for myeloma in France and Algeria before the daratumumab era.","authors":"Emilie Martin, Stéphane Morisset, Mohamad Sobh, Alfred Quillon, Hélène Boyer, Philippe Rey, Emmanuelle Nicolas Virelizier, Souad Assaad, Amine Belhabri, Yann Guillermin, Laure Lebras, Valérie Mialou, Jean-Paul Bourgeot, Mélinda Teyssier, Mohamed Brahimi, Soufi Osmani, Kamila Amani, Samira Bouchama, Lila Charef, Nabil Yafour, Badra Entasoltan, Anne Sophie Michallet, Mohamed-Amine Bekadja, Mauricette Michallet","doi":"10.1016/j.retram.2026.103566","DOIUrl":"https://doi.org/10.1016/j.retram.2026.103566","url":null,"abstract":"<p><strong>Introduction: </strong>Despite numerous therapeutic advances, first line standard care for eligible multiple myeloma (MM) patients still include high-dose melphalan and autologous stem cell transplantation (ASCT).</p><p><strong>Methods: </strong>Our study concerned MM patients who received ASCT followed or not by consolidation and maintenance, treated in two reference centers in France (Lyon n=342) and in Algeria (Oran n=452) before the daratumumab era.</p><p><strong>Results: </strong>Despite differences in resources, we showed similar long-term Overall Survival (OS) for the two groups and similar survival for patients who did not receive any chemotherapy after ASCT for relapse. After using the instant ratio, we found a longer Time to Next Treatment for Algerian patients compared to French patients. Regarding patients who relapsed after ASCT we found a significantly better OS for French patients who received up to 3 lines of treatment after ASCT compared to Algerian patients CONCLUSION: The study of long-term overall survival of MM patients after ASCT remains very useful particularly for countries for which innovative therapies including immunotherapy are not accessible, and the differences observed during ASCT management and after relapse could point to paths for improving certain clinical situations regarding the offer of MM care in these countries.</p>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"103566"},"PeriodicalIF":3.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146159168","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}
引用次数: 0
IL-10+ regulatory B lymphocytes are impacted by intradermal PBMCs therapy in patients with unexplained recurrent pregnancy loss (uRPL). 不明原因复发性妊娠丢失(uRPL)患者皮内pbmc治疗对IL-10+调节性B淋巴细胞的影响。
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-12 DOI: 10.1016/j.retram.2026.103565
Lida Aslanian-Kalkhoran, Mohammad Sadegh Soltani-Zangbar, Ali Aghebati-Maleki, Javad Ahmadian Heris, Mehdi Yousefi, Leili Aghebati-Maleki

Background: Following the confirmation of studies on the improvement of pregnancy outcomes after treatment with lymphocytes, this project aimed to assess the effectiveness of this treatment method in patients with unexplained recurrent pregnancy loss (uRPL).

Methods: After isolating B cells from 100 uRPL patients, the frequency of IL-10+B cells after treatment was measured by flow cytometry. Real-time PCR was applied to appraise the mRNA expression of microRNA and Programmed death-ligand 1(PD-L1) genes. The measurement of interleukin-10 (IL-10) secretory level in the supernatant medium was performed using the Enzyme-linked immunosorbent assay (ELISA) method.

Results: The data demonstrated that the frequency of IL-10+B cells increased after treatment with PBMCs. The expression levels of miR-10a and miR-155 were elevated in patients who received PBMCs treatments, while the levels of miR-16 and miR-21 were decreased. Furthermore, after PBMCs treatment, an increased expression level of PD-L1 was observed. The ELISA results indicated that IL-10 secretion levels increased significantly with PBMC therapy. In the group treated with PBMCs, 33 out of 50 women (66%) achieved a live birth, compared to only 15 out of 50 women (30%) in the control group.

Conclusion: In patients with uRPL, PBMCs treatment can enhance the chances of successful pregnancy by positively influencing immune regulatory factors.

背景:在证实淋巴细胞治疗改善妊娠结局的研究后,本项目旨在评估该治疗方法在不明原因复发性妊娠丢失(uRPL)患者中的有效性。方法:从100例uRPL患者中分离B细胞,用流式细胞术检测治疗后IL-10+B细胞的频率。Real-time PCR检测小鼠microRNA和程序性死亡配体1(PD-L1)基因mRNA表达情况。采用酶联免疫吸附试验(ELISA)法测定上清培养基中白细胞介素-10 (IL-10)分泌水平。结果:经pbmc处理后,IL-10+B细胞的频率增加。在接受pbmc治疗的患者中,miR-10a和miR-155的表达水平升高,而miR-16和miR-21的表达水平降低。此外,经PBMCs治疗后,PD-L1的表达水平升高。ELISA结果显示,PBMC治疗后IL-10分泌水平明显升高。在接受pbmc治疗的组中,50名妇女中有33名(66%)实现了活产,而对照组中只有15名(30%)实现了活产。结论:PBMCs治疗可通过积极影响免疫调节因子提高妊娠成功率。
{"title":"IL-10+ regulatory B lymphocytes are impacted by intradermal PBMCs therapy in patients with unexplained recurrent pregnancy loss (uRPL).","authors":"Lida Aslanian-Kalkhoran, Mohammad Sadegh Soltani-Zangbar, Ali Aghebati-Maleki, Javad Ahmadian Heris, Mehdi Yousefi, Leili Aghebati-Maleki","doi":"10.1016/j.retram.2026.103565","DOIUrl":"https://doi.org/10.1016/j.retram.2026.103565","url":null,"abstract":"<p><strong>Background: </strong>Following the confirmation of studies on the improvement of pregnancy outcomes after treatment with lymphocytes, this project aimed to assess the effectiveness of this treatment method in patients with unexplained recurrent pregnancy loss (uRPL).</p><p><strong>Methods: </strong>After isolating B cells from 100 uRPL patients, the frequency of IL-10<sup>+</sup>B cells after treatment was measured by flow cytometry. Real-time PCR was applied to appraise the mRNA expression of microRNA and Programmed death-ligand 1(PD-L1) genes. The measurement of interleukin-10 (IL-10) secretory level in the supernatant medium was performed using the Enzyme-linked immunosorbent assay (ELISA) method.</p><p><strong>Results: </strong>The data demonstrated that the frequency of IL-10<sup>+</sup>B cells increased after treatment with PBMCs. The expression levels of miR-10a and miR-155 were elevated in patients who received PBMCs treatments, while the levels of miR-16 and miR-21 were decreased. Furthermore, after PBMCs treatment, an increased expression level of PD-L1 was observed. The ELISA results indicated that IL-10 secretion levels increased significantly with PBMC therapy. In the group treated with PBMCs, 33 out of 50 women (66%) achieved a live birth, compared to only 15 out of 50 women (30%) in the control group.</p><p><strong>Conclusion: </strong>In patients with uRPL, PBMCs treatment can enhance the chances of successful pregnancy by positively influencing immune regulatory factors.</p>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"103565"},"PeriodicalIF":3.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101060","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}
引用次数: 0
Establishing hemoglobin A, F, A2 reference intervals in neonatal cord blood and clinical decision values for β-thalassemia genetic testing 建立新生儿脐带血血红蛋白A、F、A2参考区间及β-地中海贫血基因检测的临床决策价值。
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-01 DOI: 10.1016/j.retram.2026.103564
Sha Li, Jinye Xie, Yuan Tian, Weijia Wang, Juan Wang, Xing’er Wu, Renzhou Li, Man Li, Limin Li

Objective

Reference intervals for hemoglobin fractions in neonatal cord blood have been reported; however, there is no consensus on population-specific reference intervals (RIs) and laboratory-derived clinical decision values (CDVs) to guide genetic testing. Therefore, we aimed to establish RIs for HbA, HbF, and HbA2 in neonatal cord blood using a big-data-based indirect method and to determine CDVs for neonatal β-thalassemia genetic testing.

Methods

In this retrospective study, we analyzed neonatal cord blood hemoglobin electrophoresis and β-thalassemia genetic testing data collected between January 2013 and November 2024. RIs for HbA, HbF, and HbA2 were established using an indirect method, and CDVs for β-thalassemia genetic testing were determined using receiver operating characteristic (ROC) curve analysis among neonates tested for β-thalassemia.

Results

Significant sex-related differences were observed in the RIs for neonatal cord blood hemoglobin. The RIs for HbA, HbF, and HbA2 were 7.8–29.4 %, 70.8–92.0 %, and 0–0.4 % in females and 6.9–27.3 %, 72.1–93.3 %, and 0–0.3 % in males, respectively. HbA2 was not a suitable marker for β-thalassemia genetic testing due to its extremely low levels in neonatal cord blood. The CDVs for β-thalassemia genetic testing were HbA ≤ 8.1 % and HbF ≥ 90.7 % in females and HbA ≤ 7.9 % and HbF ≥ 92.0 % in males, respectively.

Conclusion

In this study, we established population-specific RIs for neonatal cord hemoglobin and proposed CDVs indicating that β-thalassemia testing is warranted when HbF ≥ 90.7 % in females or ≥ 92.0 % in males.
目的:报道新生儿脐带血血红蛋白含量的参考区间;然而,对于人群特异性参考区间(RIs)和实验室衍生的临床决策值(cdv)来指导基因检测尚无共识。因此,我们旨在利用基于大数据的间接方法建立新生儿脐带血中HbA、HbF和HbA2的RIs,并确定新生儿β-地中海贫血基因检测的cdv。方法:回顾性分析2013年1月至2024年11月收集的新生儿脐带血血红蛋白电泳和β-地中海贫血基因检测数据。采用间接法建立HbA、HbF和HbA2的RIs,采用受试者工作特征(ROC)曲线分析确定β-地中海贫血基因检测的cdv。结果:新生儿脐带血血红蛋白RIs存在显著的性别差异。女性HbA、HbF和HbA2的RIs分别为7.8- 29.4%、70.8- 92.0%和0- 0.4%,男性分别为6.9- 27.3%、72.1- 93.3%和0- 0.3%。由于新生儿脐带血中HbA2水平极低,因此不适合作为β-地中海贫血基因检测的标记物。β-地中海贫血基因检测cdv分别为:女性HbA≤8.1%、HbF≥90.7%,男性HbA≤7.9%、HbF≥92.0%。结论:在这项研究中,我们建立了新生儿脐带血红蛋白的人群特异性RIs,并提出cdv,表明当女性HbF≥90.7%或男性HbF≥92.0%时,β-地中海贫血检测是有必要的。
{"title":"Establishing hemoglobin A, F, A2 reference intervals in neonatal cord blood and clinical decision values for β-thalassemia genetic testing","authors":"Sha Li,&nbsp;Jinye Xie,&nbsp;Yuan Tian,&nbsp;Weijia Wang,&nbsp;Juan Wang,&nbsp;Xing’er Wu,&nbsp;Renzhou Li,&nbsp;Man Li,&nbsp;Limin Li","doi":"10.1016/j.retram.2026.103564","DOIUrl":"10.1016/j.retram.2026.103564","url":null,"abstract":"<div><h3>Objective</h3><div>Reference intervals for hemoglobin fractions in neonatal cord blood have been reported; however, there is no consensus on population-specific reference intervals (RIs) and laboratory-derived clinical decision values (CDVs) to guide genetic testing. Therefore, we aimed to establish RIs for HbA, HbF, and HbA2 in neonatal cord blood using a big-data-based indirect method and to determine CDVs for neonatal β-thalassemia genetic testing.</div></div><div><h3>Methods</h3><div>In this retrospective study, we analyzed neonatal cord blood hemoglobin electrophoresis and β-thalassemia genetic testing data collected between January 2013 and November 2024. RIs for HbA, HbF, and HbA2 were established using an indirect method, and CDVs for β-thalassemia genetic testing were determined using receiver operating characteristic (ROC) curve analysis among neonates tested for β-thalassemia.</div></div><div><h3>Results</h3><div>Significant sex-related differences were observed in the RIs for neonatal cord blood hemoglobin. The RIs for HbA, HbF, and HbA2 were 7.8–29.4 %, 70.8–92.0 %, and 0–0.4 % in females and 6.9–27.3 %, 72.1–93.3 %, and 0–0.3 % in males, respectively. HbA2 was not a suitable marker for β-thalassemia genetic testing due to its extremely low levels in neonatal cord blood. The CDVs for β-thalassemia genetic testing were HbA ≤ 8.1 % and HbF ≥ 90.7 % in females and HbA ≤ 7.9 % and HbF ≥ 92.0 % in males, respectively.</div></div><div><h3>Conclusion</h3><div>In this study, we established population-specific RIs for neonatal cord hemoglobin and proposed CDVs indicating that β-thalassemia testing is warranted when HbF ≥ 90.7 % in females or ≥ 92.0 % in males.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"Article 103564"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968070","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}
引用次数: 0
Lipid nanoparticle mediated delivery of Anti-CD19 CAR mRNA to umbilical blood cord NK cells for targeting CD19⁺ primary B-ALL cells 脂质纳米颗粒介导的抗CD19 CAR mRNA递送至脐带血NK细胞靶向CD19 +原代B-ALL细胞。
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-17 DOI: 10.1016/j.retram.2025.103563
Hossein Salehi-Shadkami , Mosslim Sedghi , Shima Tavoosi , Masoumeh Alimohammadi , Reza Alimohammadi , Maryam Barkhordar , Ahmadreza Mofayezi , Mohammad Sadra Modaresi , Mohammad Vaezi , Somaye Dehghanizadeh , Mohammad Ahmadvand , Vahid Khoddami
Chimeric antigen receptor natural killer (CAR-NK) cell therapy is recognized as a promising modality for the treatment of hematologic malignancies, particularly B-cell malignancies. In this study, we developed “off-the-shelf” anti-CD19 CAR-NK cells using anti-CD19 CAR mRNAs formulated in proprietary ionizable lipid nanoparticles (LNPs). The efficiency of mRNA-LNP delivery into umbilical cord blood (UCB)-derived NK cells and primary T cells was evaluated in an in vitro setting, demonstrating superior delivery efficiency in NK cells. Further investigation showed a probable role for an endocytic mechanism, macropinocytosis, in efficient transfection of NK cells with LNPs. Nevertheless, CAR-NK cells generated through this mRNA-LNP platform exhibited significantly enhanced cytotoxicity against CD19+ target cells, such as EGFP+Raji stable cell line and primary malignant B cells derived from refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL) patients. These findings highlight the promise of the mRNA-LNP platform in advancing CAR-NK therapies against B-cell malignancies.
嵌合抗原受体自然杀伤(CAR-NK)细胞疗法被认为是治疗血液系统恶性肿瘤,特别是b细胞恶性肿瘤的一种有前途的方式。在这项研究中,我们使用专有的可电离脂质纳米颗粒(LNPs)配制的抗cd19 CAR- nk mrna开发了“现成的”抗cd19 CAR- nk细胞。在体外环境中评估mRNA-LNP在脐带血(UCB)来源的NK细胞和原代T细胞中的递送效率,显示出在NK细胞中的优越递送效率。进一步的研究表明,在LNPs有效转染NK细胞中,内吞机制巨噬作用可能起作用。然而,通过mRNA-LNP平台生成的CAR-NK细胞对CD19+靶细胞(如EGFP+Raji稳定细胞系和来自难治性/复发性B细胞急性淋巴细胞白血病(B- all)患者的原发性恶性B细胞)表现出显著增强的细胞毒性。这些发现突出了mRNA-LNP平台在推进CAR-NK治疗b细胞恶性肿瘤方面的前景。
{"title":"Lipid nanoparticle mediated delivery of Anti-CD19 CAR mRNA to umbilical blood cord NK cells for targeting CD19⁺ primary B-ALL cells","authors":"Hossein Salehi-Shadkami ,&nbsp;Mosslim Sedghi ,&nbsp;Shima Tavoosi ,&nbsp;Masoumeh Alimohammadi ,&nbsp;Reza Alimohammadi ,&nbsp;Maryam Barkhordar ,&nbsp;Ahmadreza Mofayezi ,&nbsp;Mohammad Sadra Modaresi ,&nbsp;Mohammad Vaezi ,&nbsp;Somaye Dehghanizadeh ,&nbsp;Mohammad Ahmadvand ,&nbsp;Vahid Khoddami","doi":"10.1016/j.retram.2025.103563","DOIUrl":"10.1016/j.retram.2025.103563","url":null,"abstract":"<div><div>Chimeric antigen receptor natural killer (CAR-NK) cell therapy is recognized as a promising modality for the treatment of hematologic malignancies, particularly B-cell malignancies. In this study, we developed “off-the-shelf” anti-CD19 CAR-NK cells using anti-CD19 CAR mRNAs formulated in proprietary ionizable lipid nanoparticles (LNPs). The efficiency of mRNA-LNP delivery into umbilical cord blood (UCB)-derived NK cells and primary T cells was evaluated in an in vitro setting, demonstrating superior delivery efficiency in NK cells. Further investigation showed a probable role for an endocytic mechanism, macropinocytosis, in efficient transfection of NK cells with LNPs. Nevertheless, CAR-NK cells generated through this mRNA-LNP platform exhibited significantly enhanced cytotoxicity against CD19<sup>+</sup> target cells, such as EGFP<sup>+</sup>Raji stable cell line and primary malignant B cells derived from refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL) patients. These findings highlight the promise of the mRNA-LNP platform in advancing CAR-NK therapies against B-cell malignancies.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"Article 103563"},"PeriodicalIF":3.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806490","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}
引用次数: 0
Integrating CAR-T cells with other immunotherapies for improved efficacy in cancer patients 将CAR-T细胞与其他免疫疗法相结合,提高癌症患者的疗效。
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-16 DOI: 10.1016/j.retram.2025.103562
Gagandeep Singh , Lata Kumari , Dipansh Katoch , Arshiya Sood , Neelam Thakur , Kaalindi Singh , Umesh Kumar
Chimeric Antigen Receptor (CAR) T cell therapy is a novel cum innovative treatment for cancer patients, especially the ones dealing with blood cancers. However, solid tumours remain an area where this therapy is not so effective. The challenges are antigen heterogeneity, immunosuppressive tumour microenvironment, and some unaddressed serious side effects. This study details how different immunotherapeutic approaches can be used in synergy with each other to augment efficacy of CAR-T cell-based therapy and to minimize its limitations as a standalone therapy. Our review looks at how immune checkpoint inhibitors (ICIs), cytokine-based approaches, hematopoietic stem cell transplantation (HSCT), cancer vaccines, oncolytic viruses, monoclonal antibodies, NK cell therapy, tumour-infiltrating lymphocytes, bispecific T-cell engagers (BiTEs), and oncolytic viruses (OVs) could be utilized together with CAR-T cell therapy. Reducing repressive cell populations and improving antigen presentation helps OVs modify the TME, enabling better CAR-T cell penetration and persistence. Similar to this, BiTEs deal with issues of antigen loss and relapse by increasing the number of cells that target antigens and bringing in bystander T-cells. Moreover, cytokine co-delivery and changes inside cells show promise in lowering systemic toxicity and increasing continuous CAR-T activation. Early-stage clinical trials and preclinical studies show that these combinatorial strategies may work, but there are still issues like dose-dependent toxicity, exact treatment timing, and delivery restrictions. This review highlights generally the possibilities of combinational techniques to greatly increase the efficacy and safety profile of CAR-T cell treatments, thus providing insightful information for next studies and clinical uses in cancer immunotherapy.
嵌合抗原受体(CAR - T)细胞疗法是一种新的治疗癌症的创新疗法,特别是治疗血癌。然而,这种疗法在实体肿瘤领域仍然不是很有效。挑战是抗原异质性、免疫抑制肿瘤微环境和一些未解决的严重副作用。本研究详细介绍了不同的免疫治疗方法如何相互协同使用,以增强基于CAR-T细胞治疗的疗效,并最大限度地减少其作为单独治疗的局限性。我们的综述着眼于免疫检查点抑制剂(ICIs)、基于细胞因子的方法、造血干细胞移植(HSCT)、癌症疫苗、溶瘤病毒、单克隆抗体、NK细胞治疗、肿瘤浸润淋巴细胞、双特异性t细胞参与细胞(BiTEs)和溶瘤病毒(OVs)如何与CAR-T细胞治疗一起使用。减少抑制性细胞群和改善抗原呈递有助于OVs修饰TME,使CAR-T细胞更好地渗透和持久性。与此类似,bite通过增加靶向抗原的细胞数量和引入旁观者t细胞来处理抗原丢失和复发的问题。此外,细胞因子的共传递和细胞内的变化显示出降低全身毒性和增加CAR-T持续激活的希望。早期临床试验和临床前研究表明,这些组合策略可能有效,但仍存在剂量依赖性毒性、确切的治疗时间和给药限制等问题。这篇综述一般强调了联合技术大大提高CAR-T细胞治疗的有效性和安全性的可能性,从而为下一步研究和癌症免疫治疗的临床应用提供了有见地的信息。
{"title":"Integrating CAR-T cells with other immunotherapies for improved efficacy in cancer patients","authors":"Gagandeep Singh ,&nbsp;Lata Kumari ,&nbsp;Dipansh Katoch ,&nbsp;Arshiya Sood ,&nbsp;Neelam Thakur ,&nbsp;Kaalindi Singh ,&nbsp;Umesh Kumar","doi":"10.1016/j.retram.2025.103562","DOIUrl":"10.1016/j.retram.2025.103562","url":null,"abstract":"<div><div>Chimeric Antigen Receptor (CAR) T cell therapy is a novel cum innovative treatment for cancer patients, especially the ones dealing with blood cancers. However, solid tumours remain an area where this therapy is not so effective. The challenges are antigen heterogeneity, immunosuppressive tumour microenvironment, and some unaddressed serious side effects. This study details how different immunotherapeutic approaches can be used in synergy with each other to augment efficacy of CAR-T cell-based therapy and to minimize its limitations as a standalone therapy. Our review looks at how immune checkpoint inhibitors (ICIs), cytokine-based approaches, hematopoietic stem cell transplantation (HSCT), cancer vaccines, oncolytic viruses, monoclonal antibodies, NK cell therapy, tumour-infiltrating lymphocytes, bispecific T-cell engagers (BiTEs), and oncolytic viruses (OVs) could be utilized together with CAR-T cell therapy. Reducing repressive cell populations and improving antigen presentation helps OVs modify the TME, enabling better CAR-T cell penetration and persistence. Similar to this, BiTEs deal with issues of antigen loss and relapse by increasing the number of cells that target antigens and bringing in bystander T-cells. Moreover, cytokine co-delivery and changes inside cells show promise in lowering systemic toxicity and increasing continuous CAR-T activation. Early-stage clinical trials and preclinical studies show that these combinatorial strategies may work, but there are still issues like dose-dependent toxicity, exact treatment timing, and delivery restrictions. This review highlights generally the possibilities of combinational techniques to greatly increase the efficacy and safety profile of CAR-T cell treatments, thus providing insightful information for next studies and clinical uses in cancer immunotherapy.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"Article 103562"},"PeriodicalIF":3.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822003","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}
引用次数: 0
Nanoparticle albumin-bound paclitaxel (nab-Paclitaxel): Bridging pharmacology and translational medicine in breast cancer 纳米颗粒白蛋白结合紫杉醇:乳腺癌的桥接药理学和转化医学。
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-15 DOI: 10.1016/j.retram.2025.103561
Ali G. Alkhathami , Abdulrahman T. Ahmed , Ahmed Hussein , Roopashree R , Prakhar Tomar , Hussein Riyadh Abdul Kareem Al-Hetty , Rajashree Panigrahi , Ashish Singh Chauhan , Fathi Jihad Hammady , Salah Abdulhadi Salih
Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) represents a significant advancement in breast cancer therapy by enhancing drug delivery and minimizing solvent-related toxicity. Utilizing albumin-mediated transcytosis, nab-paclitaxel achieves superior intratumoral accumulation while eliminating hypersensitivity reactions linked to solvent-based taxanes. Clinical trials in metastatic breast cancer have demonstrated higher response rates and improved tolerability compared with conventional paclitaxel, especially in HER2-negative and triple-negative subtypes. In neoadjuvant settings, nab-paclitaxel-based regimens yield higher pCR rates and exhibit synergistic efficacy when combined with carboplatin, anthracyclines, or immune checkpoint inhibitors. Safety analyses show a favorable profile with reduced myelosuppression but an increased risk of peripheral neuropathy in certain populations. Additionally, nab-paclitaxel has been effectively incorporated into immunotherapy regimens for TNBC and HER2-targeted strategies in HER2-positive disease. Pharmacokinetic studies reveal improved tissue distribution and higher unbound paclitaxel exposure compared to solvent-based formulations. Overall, nab-paclitaxel offers distinct therapeutic advantages in terms of efficacy, safety, and tumor targeting, representing a major step forward in overcoming resistance and optimizing breast cancer treatment.
纳米颗粒白蛋白结合紫杉醇(nab-paclitaxel)通过增强药物传递和减少溶剂相关毒性,在乳腺癌治疗中取得了重大进展。利用白蛋白介导的胞吞作用,nab-紫杉醇在消除与溶剂型紫杉醇相关的超敏反应的同时,实现了优越的肿瘤内积累。转移性乳腺癌的临床试验表明,与传统紫杉醇相比,转移性乳腺癌的反应率更高,耐受性更好,特别是在her2阴性和三阴性亚型中。在新辅助治疗中,以nab-紫杉醇为基础的方案在与卡铂、蒽环类药物或免疫检查点抑制剂联合使用时产生更高的pCR率和协同效应。安全性分析显示,在某些人群中,骨髓抑制减少,但周围神经病变的风险增加。此外,nab-紫杉醇已被有效地纳入针对TNBC和her2阳性疾病的免疫治疗方案中。药代动力学研究表明,与溶剂型制剂相比,改善了组织分布和更高的非结合紫杉醇暴露。总的来说,nab-紫杉醇在疗效、安全性和肿瘤靶向性方面具有明显的治疗优势,在克服耐药和优化乳腺癌治疗方面迈出了重要的一步。
{"title":"Nanoparticle albumin-bound paclitaxel (nab-Paclitaxel): Bridging pharmacology and translational medicine in breast cancer","authors":"Ali G. Alkhathami ,&nbsp;Abdulrahman T. Ahmed ,&nbsp;Ahmed Hussein ,&nbsp;Roopashree R ,&nbsp;Prakhar Tomar ,&nbsp;Hussein Riyadh Abdul Kareem Al-Hetty ,&nbsp;Rajashree Panigrahi ,&nbsp;Ashish Singh Chauhan ,&nbsp;Fathi Jihad Hammady ,&nbsp;Salah Abdulhadi Salih","doi":"10.1016/j.retram.2025.103561","DOIUrl":"10.1016/j.retram.2025.103561","url":null,"abstract":"<div><div>Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) represents a significant advancement in breast cancer therapy by enhancing drug delivery and minimizing solvent-related toxicity. Utilizing albumin-mediated transcytosis, nab-paclitaxel achieves superior intratumoral accumulation while eliminating hypersensitivity reactions linked to solvent-based taxanes. Clinical trials in metastatic breast cancer have demonstrated higher response rates and improved tolerability compared with conventional paclitaxel, especially in HER2-negative and triple-negative subtypes. In neoadjuvant settings, nab-paclitaxel-based regimens yield higher pCR rates and exhibit synergistic efficacy when combined with carboplatin, anthracyclines, or immune checkpoint inhibitors. Safety analyses show a favorable profile with reduced myelosuppression but an increased risk of peripheral neuropathy in certain populations. Additionally, nab-paclitaxel has been effectively incorporated into immunotherapy regimens for TNBC and HER2-targeted strategies in HER2-positive disease. Pharmacokinetic studies reveal improved tissue distribution and higher unbound paclitaxel exposure compared to solvent-based formulations. Overall, nab-paclitaxel offers distinct therapeutic advantages in terms of efficacy, safety, and tumor targeting, representing a major step forward in overcoming resistance and optimizing breast cancer treatment.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"Article 103561"},"PeriodicalIF":3.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835323","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}
引用次数: 0
Artificial intelligence for anemia screening, diagnosis, and management 用于贫血筛查、诊断和管理的人工智能。
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-07 DOI: 10.1016/j.retram.2025.103560
David B. Olawade , Yinka Julianah Adeniji , Faithful A. Olatunbosun , Eghosasere Egbon , Aanuoluwapo Clement David-Olawade
Anemia affects over 1.6 billion people globally, representing a significant public health challenge, particularly in low- and middle-income countries where traditional diagnostic methods face barriers including invasive procedures, skilled personnel requirements, and inadequate laboratory infrastructure. Artificial intelligence (AI) has emerged as a promising technology offering non-invasive, rapid, and cost-effective solutions for anemia detection and management. This narrative review synthesises current literature on AI applications in anemia screening, diagnosis, and clinical management, examining methodologies, performance metrics, implementation challenges, and future research directions. We conducted a comprehensive narrative synthesis informed by systematic search principles, searching PubMed, IEEE Xplore, Scopus, and Web of Science databases with additional hand-searching and expert consultation. AI models demonstrate variable accuracy in anemia detection across diverse data sources, with performance ranging from 75–97 % AUC depending on methodology and validation approaches. Machine learning algorithms such as support vector machines, convolutional neural networks, and random forests show potential for achieving performance comparable to standard blood tests in controlled research settings. Smartphone-integrated applications and point-of-care systems show particular promise for resource-limited settings, though real-world validation remains limited. While AI shows significant potential for enhancing accessibility and diagnostic efficiency in anemia care, critical challenges including data standardisation, algorithmic bias, regulatory compliance, clinical validation in diverse populations, and deployment equity in low- and middle-income countries require urgent attention to ensure equitable implementation and clinical adoption.
贫血影响全球超过16亿人,是一项重大的公共卫生挑战,特别是在传统诊断方法面临包括侵入性手术、熟练人员需求和实验室基础设施不足等障碍的低收入和中等收入国家。人工智能(AI)已经成为一种有前途的技术,为贫血的检测和管理提供了非侵入性、快速和经济的解决方案。本文综述了人工智能在贫血筛查、诊断和临床管理、检查方法、绩效指标、实施挑战和未来研究方向等方面的应用。我们根据系统的检索原则进行了全面的叙述综合,检索了PubMed、IEEE Xplore、Scopus和Web of Science数据库,并进行了额外的手工检索和专家咨询。人工智能模型在不同数据源的贫血检测中显示出不同的准确性,根据方法和验证方法的不同,其性能在75- 97%的AUC之间。支持向量机、卷积神经网络和随机森林等机器学习算法显示出在受控研究环境中实现与标准血液测试相当的性能的潜力。智能手机集成应用程序和护理点系统在资源有限的环境中显示出特别的前景,尽管实际验证仍然有限。虽然人工智能在提高贫血护理的可及性和诊断效率方面显示出巨大潜力,但迫切需要关注包括数据标准化、算法偏差、法规遵从性、不同人群的临床验证以及低收入和中等收入国家部署公平性在内的关键挑战,以确保公平实施和临床采用。
{"title":"Artificial intelligence for anemia screening, diagnosis, and management","authors":"David B. Olawade ,&nbsp;Yinka Julianah Adeniji ,&nbsp;Faithful A. Olatunbosun ,&nbsp;Eghosasere Egbon ,&nbsp;Aanuoluwapo Clement David-Olawade","doi":"10.1016/j.retram.2025.103560","DOIUrl":"10.1016/j.retram.2025.103560","url":null,"abstract":"<div><div>Anemia affects over 1.6 billion people globally, representing a significant public health challenge, particularly in low- and middle-income countries where traditional diagnostic methods face barriers including invasive procedures, skilled personnel requirements, and inadequate laboratory infrastructure. Artificial intelligence (AI) has emerged as a promising technology offering non-invasive, rapid, and cost-effective solutions for anemia detection and management. This narrative review synthesises current literature on AI applications in anemia screening, diagnosis, and clinical management, examining methodologies, performance metrics, implementation challenges, and future research directions. We conducted a comprehensive narrative synthesis informed by systematic search principles, searching PubMed, IEEE Xplore, Scopus, and Web of Science databases with additional hand-searching and expert consultation. AI models demonstrate variable accuracy in anemia detection across diverse data sources, with performance ranging from 75–97 % AUC depending on methodology and validation approaches. Machine learning algorithms such as support vector machines, convolutional neural networks, and random forests show potential for achieving performance comparable to standard blood tests in controlled research settings. Smartphone-integrated applications and point-of-care systems show particular promise for resource-limited settings, though real-world validation remains limited. While AI shows significant potential for enhancing accessibility and diagnostic efficiency in anemia care, critical challenges including data standardisation, algorithmic bias, regulatory compliance, clinical validation in diverse populations, and deployment equity in low- and middle-income countries require urgent attention to ensure equitable implementation and clinical adoption.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"Article 103560"},"PeriodicalIF":3.0,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769976","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}
引用次数: 0
Corrigendum to “AI-assisted statistical review of 100 oncology research articles: compliance with SAMPL guidelines” [Current Research in Translational Medicine 73 (2025) 103544] “100篇肿瘤学研究文章的人工智能辅助统计审查:符合SAMPL指南”的勘误表[当前转化医学研究73(2025)103544]。
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-04 DOI: 10.1016/j.retram.2025.103558
Michal Ordak
{"title":"Corrigendum to “AI-assisted statistical review of 100 oncology research articles: compliance with SAMPL guidelines” [Current Research in Translational Medicine 73 (2025) 103544]","authors":"Michal Ordak","doi":"10.1016/j.retram.2025.103558","DOIUrl":"10.1016/j.retram.2025.103558","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"Article 103558"},"PeriodicalIF":3.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688733","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}
引用次数: 0
The efficacy and safety of anti-CD38 monoclonal antibodies in transplant-ineligible newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials 抗cd38单克隆抗体在不适合移植的新诊断多发性骨髓瘤中的疗效和安全性:随机对照试验的系统回顾和荟萃分析
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-02 DOI: 10.1016/j.retram.2025.103559
Turkan Aliyeva , Haroon Alamy , Feras Ahmad Ibrahim Ahmad , Julia Natche , Hafiz Shah , Vrushali Shelar , Huu Than Huynh , Imane El Amri

Background

Treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) remains challenging due to age, frailty, and comorbidities. Anti-CD38 monoclonal antibodies, particularly daratumumab, have emerged as promising additions to frontline regimens. However, the long-term outcomes of these therapies are still uncertain. This systematic review and meta-analysis aimed to compare the survival outcome of anti-CD38 antibodies in TIE-NDMM patients.

Methods

We systematically searched PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) published up to April 2025 comparing anti-CD38 mAbs based regimens versus standard therapy in transplant-ineligible NDMM patients. A random-effects model was used to calculate pooled hazard ratios (HRs) with 95 % confidence intervals (CIs).

Results

A total of six RCTs with 2,625 patients were included in the analysis. Of these, 1,390 (52.9 %) patients received anti-CD38-based regimens. The follow-up duration varied from 41.2 to 86.7 months across the studies. Compared to standard therapy, anti-CD38-based regimens significantly improved both overall survival (OS) (HR 0.70; 95 % CI 0.58–0.84; p=0.0002; I² = 46 %) and progression-free survival (PFS) (HR 0.57; 95 % CI 0.51–0.65; p < 0.00001; I² = 15 %). The pooled results demonstrated that non-frail patients had a longer PFS than frail patients (HR = 0.46; 95 % CI, 0.34–0.63 and HR = 0.55; 95 % CI, 0.45–0.67, respectively), although the difference between the subgroups was not statistically significant (p = 0.36).

Conclusion

In transplant-ineligible NDMM patients, the addition of anti-CD38 monoclonal antibodies to standard regimens significantly improves clinical outcomes. These findings support the integration of anti-CD38 therapy into first-line treatment for this vulnerable patient population.
背景:由于年龄、虚弱和合并症,新诊断的不适合移植的多发性骨髓瘤(TIE-NDMM)的治疗仍然具有挑战性。抗cd38单克隆抗体,特别是达拉单抗,已经成为一线治疗方案中有希望的补充。然而,这些疗法的长期效果仍不确定。本系统综述和荟萃分析旨在比较TIE-NDMM患者中抗cd38抗体的生存结局。方法:我们系统地检索PubMed、Embase和Cochrane图书馆数据库,检索截至2025年4月发表的随机对照试验(rct),比较基于抗cd38单抗的方案与标准治疗在不适合移植的NDMM患者中的效果。采用随机效应模型计算95%置信区间(ci)的合并风险比(hr)。结果共纳入6项随机对照试验,共纳入2625例患者。其中,1390例(52.9%)患者接受了基于抗cd38的治疗方案。这些研究的随访时间从41.2个月到86.7个月不等。与标准治疗相比,基于抗cd38的方案显著改善了总生存期(OS) (HR 0.70; 95% CI 0.58-0.84; p=0.0002; I²= 46%)和无进展生存期(PFS) (HR 0.57; 95% CI 0.51-0.65; p < 0.00001; I²= 15%)。合并结果显示,非体弱患者的PFS较体弱患者长(HR = 0.46, 95% CI分别为0.34-0.63和HR = 0.55, 95% CI分别为0.45-0.67),但亚组间差异无统计学意义(p = 0.36)。结论对于不适合移植的NDMM患者,在标准方案中加入抗cd38单克隆抗体可显著改善临床预后。这些发现支持将抗cd38疗法整合到这一弱势患者群体的一线治疗中。
{"title":"The efficacy and safety of anti-CD38 monoclonal antibodies in transplant-ineligible newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials","authors":"Turkan Aliyeva ,&nbsp;Haroon Alamy ,&nbsp;Feras Ahmad Ibrahim Ahmad ,&nbsp;Julia Natche ,&nbsp;Hafiz Shah ,&nbsp;Vrushali Shelar ,&nbsp;Huu Than Huynh ,&nbsp;Imane El Amri","doi":"10.1016/j.retram.2025.103559","DOIUrl":"10.1016/j.retram.2025.103559","url":null,"abstract":"<div><h3>Background</h3><div>Treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) remains challenging due to age, frailty, and comorbidities. Anti-CD38 monoclonal antibodies, particularly daratumumab, have emerged as promising additions to frontline regimens. However, the long-term outcomes of these therapies are still uncertain. This systematic review and meta-analysis aimed to compare the survival outcome of anti-CD38 antibodies in TIE-NDMM patients.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) published up to April 2025 comparing anti-CD38 mAbs based regimens versus standard therapy in transplant-ineligible NDMM patients. A random-effects model was used to calculate pooled hazard ratios (HRs) with 95 % confidence intervals (CIs).</div></div><div><h3>Results</h3><div>A total of six RCTs with 2,625 patients were included in the analysis. Of these, 1,390 (52.9 %) patients received anti-CD38-based regimens. The follow-up duration varied from 41.2 to 86.7 months across the studies. Compared to standard therapy, anti-CD38-based regimens significantly improved both overall survival (OS) (HR 0.70; 95 % CI 0.58–0.84; p=0.0002; I² = 46 %) and progression-free survival (PFS) (HR 0.57; 95 % CI 0.51–0.65; p &lt; 0.00001; I² = 15 %). The pooled results demonstrated that non-frail patients had a longer PFS than frail patients (HR = 0.46; 95 % CI, 0.34–0.63 and HR = 0.55; 95 % CI, 0.45–0.67, respectively), although the difference between the subgroups was not statistically significant (p = 0.36).</div></div><div><h3>Conclusion</h3><div>In transplant-ineligible NDMM patients, the addition of anti-CD38 monoclonal antibodies to standard regimens significantly improves clinical outcomes. These findings support the integration of anti-CD38 therapy into first-line treatment for this vulnerable patient population<strong>.</strong></div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"74 1","pages":"Article 103559"},"PeriodicalIF":3.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736905","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}
引用次数: 0
Bone marrow vacuolization to curative strategies: Evolving paradigms in VEXAS syndrome management. 骨髓空泡化到治疗策略:在VEXAS综合征管理中的演变范例。
IF 3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-01 Epub Date: 2025-07-30 DOI: 10.1016/j.retram.2025.103533
Mahmoud I Elbadry, Mohamed Mabed

VEXAS syndrome (vacuoles, E1 enzyme, X-linked alongside autoinflammatory and somatic) is a severe aggressive inflammation disorder arising in adults that results from acquired changes to the UBA1 gene. These genetic alterations lead to widespread chronic systemic inflammation, prominent features of clonal hematopoiesis, and worsening cytopenic decays alongside hematological malignancies. The grim prognosis includes survival-seeking patients facing life-threatening infections, bone marrow failure or thrombotic complications with only 76 % three-year survival rate. It mainly occurs in older men but rare cases in women stem from atypical patterns of X-chromosome inactivation. This syndrome shares characteristics with autoimmune disorders like relapsing polychondritis and blood disorders predominantly myelodysplastic syndromes. Diagnosis requires UBA1 genetic analysis and bone marrow examination which shows characteristic vacuolization in myeloid and erythroid progenitors. Current therapeutic approaches concentrate on fighting inflammation alongside supportive therapy. This includes infection control, transfusion administration, hypomethylating agents such as azacitidine, which provide the dual benefit of reducing mutant clones alongside inflammation, as well as immunosuppressive drugs, steroids, and Janus Kinase (JAK) inhibitors. Even though allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole option for a cure, its extensive toxicity limits widespread application. Some investigational therapies targeting specific pathways show promise, particularly nucleotide-binding domain, Leucine-rich Repeat-containing family, pyrin domain containing 3 (NLRP3) inflammasome blockers (IL-1β/IL-6 inhibitors) and proteasome inhibitors like bortezomib (Bortezomib), which exploit the proteostasis defects in UBA1-mutated cells. Core obstacles still lie in the absence of a standardized treatment paradigm due to gaps in genotype-phenotype expression and variability, alongside insufficient biomarkers able to guide therapy selection and directed personalized therapeutic interventions. This review highlights the curative strategies, therapeutic challenges, and advancements in VEXAS syndrome, underscoring the urgent need for targeted strategies to improve the patient outcomes.

VEXAS综合征(空泡,E1酶,x连锁伴随自身炎症和躯体炎症)是一种严重的侵袭性炎症疾病,发生于成人,由获得性UBA1基因改变引起。这些基因改变导致广泛的慢性全身性炎症,突出的克隆造血特征,以及与血液系统恶性肿瘤一起恶化的细胞减少性衰退。严峻的预后包括寻求生存的患者面临危及生命的感染,骨髓衰竭或血栓性并发症,只有76%的三年生存率。它主要发生在老年男性中,但在女性中罕见的病例源于非典型的x染色体失活模式。该综合征与自身免疫性疾病如复发性多软骨炎和以骨髓增生异常综合征为主的血液疾病有共同的特征。诊断需要UBA1基因分析和骨髓检查,骨髓和红细胞祖细胞显示特征性空泡化。目前的治疗方法集中在对抗炎症和支持治疗。这包括感染控制、输血管理、低甲基化药物,如阿扎胞苷,它提供了减少突变克隆和炎症的双重好处,以及免疫抑制药物、类固醇和Janus激酶(JAK)抑制剂。尽管同种异体造血干细胞移植(HSCT)仍然是唯一的治疗选择,但其广泛的毒性限制了其广泛应用。一些针对特定途径的研究性治疗显示出希望,特别是核苷酸结合域,富含亮氨酸的重复-含家族,pyrin结构域3 (NLRP3)炎性体阻滞剂(IL-1β/IL-6抑制剂)和蛋白酶体抑制剂,如硼替佐米(硼替佐米),它们利用uba1突变细胞中的蛋白质平衡缺陷。核心障碍仍然在于缺乏标准化的治疗模式,这是由于基因型-表型表达和可变性方面的差距,以及能够指导治疗选择和指导个性化治疗干预的生物标志物不足。这篇综述强调了VEXAS综合征的治疗策略、治疗挑战和进展,强调了迫切需要有针对性的策略来改善患者的预后。
{"title":"Bone marrow vacuolization to curative strategies: Evolving paradigms in VEXAS syndrome management.","authors":"Mahmoud I Elbadry, Mohamed Mabed","doi":"10.1016/j.retram.2025.103533","DOIUrl":"10.1016/j.retram.2025.103533","url":null,"abstract":"<p><p>VEXAS syndrome (vacuoles, E1 enzyme, X-linked alongside autoinflammatory and somatic) is a severe aggressive inflammation disorder arising in adults that results from acquired changes to the UBA1 gene. These genetic alterations lead to widespread chronic systemic inflammation, prominent features of clonal hematopoiesis, and worsening cytopenic decays alongside hematological malignancies. The grim prognosis includes survival-seeking patients facing life-threatening infections, bone marrow failure or thrombotic complications with only 76 % three-year survival rate. It mainly occurs in older men but rare cases in women stem from atypical patterns of X-chromosome inactivation. This syndrome shares characteristics with autoimmune disorders like relapsing polychondritis and blood disorders predominantly myelodysplastic syndromes. Diagnosis requires UBA1 genetic analysis and bone marrow examination which shows characteristic vacuolization in myeloid and erythroid progenitors. Current therapeutic approaches concentrate on fighting inflammation alongside supportive therapy. This includes infection control, transfusion administration, hypomethylating agents such as azacitidine, which provide the dual benefit of reducing mutant clones alongside inflammation, as well as immunosuppressive drugs, steroids, and Janus Kinase (JAK) inhibitors. Even though allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole option for a cure, its extensive toxicity limits widespread application. Some investigational therapies targeting specific pathways show promise, particularly nucleotide-binding domain, Leucine-rich Repeat-containing family, pyrin domain containing 3 (NLRP3) inflammasome blockers (IL-1β/IL-6 inhibitors) and proteasome inhibitors like bortezomib (Bortezomib), which exploit the proteostasis defects in UBA1-mutated cells. Core obstacles still lie in the absence of a standardized treatment paradigm due to gaps in genotype-phenotype expression and variability, alongside insufficient biomarkers able to guide therapy selection and directed personalized therapeutic interventions. This review highlights the curative strategies, therapeutic challenges, and advancements in VEXAS syndrome, underscoring the urgent need for targeted strategies to improve the patient outcomes.</p>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 4","pages":"103533"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818245","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}
引用次数: 0
期刊
Current Research in Translational Medicine
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1