Leukemia & LymphomaPub Date : 2025-04-01Epub Date: 2024-12-22DOI: 10.1080/10428194.2024.2443550
Saurabh Zanwar, Shaji Kumar
{"title":"Risk-adapted treatment for multiple myeloma: assessing the current potential and a roadmap for the future.","authors":"Saurabh Zanwar, Shaji Kumar","doi":"10.1080/10428194.2024.2443550","DOIUrl":"10.1080/10428194.2024.2443550","url":null,"abstract":"<p><p>Over the past two decades, new agents for multiple myeloma (MM) have significantly improved patient outcomes, particularly for those with standard-risk disease, who now have a median overall survival of over a decade. However, this benefit is less pronounced in high-risk and ultra-high-risk MM, where median survival ranges from 3 to 5 years. The definition of HRMM continues to evolve and is driven by the genomic features, disease burden, and medical comorbidities. Various risk stratification tools are available to gauge the risk status of the disease. Recently, a slew of single-arm phase 2 trials for high-risk MM have been reported with a general theme of intensification of various phases of treatment. Additionally, minimal residual disease testing in treatment escalation/de-escalation is being actively investigated. This review summarizes the existing evidence for risk-adapted treatment in patients with MM.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"573-583"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877334","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}
Leukemia & LymphomaPub Date : 2025-04-01Epub Date: 2024-12-06DOI: 10.1080/10428194.2024.2434171
Joshua A Fein, Agnes McAuliffe, Kimberly Fischer, Owen Brady, Sean M Devlin, Silvia Willumsen, Gonca Ozcan, Pat Montanaro, Yelena Pristyazhnyuk, Joseph DiGiuseppe, Oscar B Lahoud, Miguel-Angel Perales, David G Pfister, Sergio Giralt, Mark Dailey, Peter Paul Yu, Craig Steven Sauter
{"title":"A Shared Care Model between community and transplant centers facilitates access to allogeneic and autologous transplantation.","authors":"Joshua A Fein, Agnes McAuliffe, Kimberly Fischer, Owen Brady, Sean M Devlin, Silvia Willumsen, Gonca Ozcan, Pat Montanaro, Yelena Pristyazhnyuk, Joseph DiGiuseppe, Oscar B Lahoud, Miguel-Angel Perales, David G Pfister, Sergio Giralt, Mark Dailey, Peter Paul Yu, Craig Steven Sauter","doi":"10.1080/10428194.2024.2434171","DOIUrl":"10.1080/10428194.2024.2434171","url":null,"abstract":"<p><p>Access to allogeneic and autologous hematopoietic stem cell transplantation (SCT) remains inadequate despite its curative potential across hematologic malignancies. In 2015, Hartford HealthCare (HHC) and the Memorial Sloan Kettering Cancer Center (MSK) established the Shared Care Model (SCM) with a primary aim of enhancing SCT access for HHC patients. The SCM comprises several components: an SCT-dedicated nurse-navigator, a health-information exchange for record sharing, telemedicine, and ongoing training of HHC clinicians in transplant patient selection and management. We evaluated the SCM's impact on SCT access across 126 patients with acute leukemia, myelodysplastic syndrome, and multiple myeloma from 2016-2020. The SCM facilitated 34 referrals. Socio-economic status of HHC referrals by Area Deprivation Index was significantly inferior (38 vs. 14, <i>p</i> < 0.001) when compared to 3,108 non-SCM referrals to MSK during the same period. Allogeneic recipients spent 68-247 days away from home, and autologous recipients 15-48, both requiring few subsequent visits to MSK.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"713-720"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785591","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}
Leukemia & LymphomaPub Date : 2025-04-01Epub Date: 2024-12-09DOI: 10.1080/10428194.2024.2436034
Wolfgang Knauf, Jens Uhlig, Eyck von der Heyde, Christoph Losem, Andreas Ammon, Arnd Nusch, Rudolf Schlag, Holger Schulz, Jan Janssen, Manfred Welslau, Stefan Wilop, Corinne Vannier, Hans Ulrich Siebenbach, Laura Serrer, Anita Schuch, Sandra Maria Woerner, Monika Engelhardt, Karin Potthoff
{"title":"Treatment adherence and effectiveness in patients treated with carfilzomib-based therapy combinations for relapsed/refractory multiple myeloma in Germany: interim results from the non-interventional CARO study.","authors":"Wolfgang Knauf, Jens Uhlig, Eyck von der Heyde, Christoph Losem, Andreas Ammon, Arnd Nusch, Rudolf Schlag, Holger Schulz, Jan Janssen, Manfred Welslau, Stefan Wilop, Corinne Vannier, Hans Ulrich Siebenbach, Laura Serrer, Anita Schuch, Sandra Maria Woerner, Monika Engelhardt, Karin Potthoff","doi":"10.1080/10428194.2024.2436034","DOIUrl":"10.1080/10428194.2024.2436034","url":null,"abstract":"<p><p>Therapy adherence can significantly influence the outcome of cancer patients. The prospective, non-interventional CARO study (NCT02970747) investigated adherence, effectiveness, and safety of carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) in the German real-world setting. In total, 359 patients were included at 69 sites. Data on carfilzomib combination regimens were evaluated for three treatment cohorts: carfilzomib with lenalidomide and dexamethasone (KRd), with dexamethasone only (Kd) or with daratumumab and dexamethasone (KdD). Encouragingly, patients maintained levels of treatment adherence ≥95% to carfilzomib across cohorts. The effectiveness outcomes of CARO were in line with previous data. Median PFS (95% CI) was 17.5 months (14.5, 24.7 [KRd]), 13.4 months (7.0, 18.1 [Kd]), and 15.6 months (9.9, NA [KdD]), respectively. Median OS was 38.9 months (31.5, 53.9 [KRd]), 24.2 months (17.3, 36.8 [Kd]), and not reached (KdD). Overall, the CARO study impressively demonstrates efficacy and safety of KRd, Kd, and KdD regimen in real-world.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"691-701"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801289","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}
Leukemia & LymphomaPub Date : 2025-04-01Epub Date: 2024-12-17DOI: 10.1080/10428194.2024.2438804
Maria Dampmann, Artur Kibler, Julia von Tresckow, Hans Christian Reinhardt, Ralf Küppers, Bettina Budeus
{"title":"Single-cell analysis of a bi-clonal chronic lymphocytic leukemia reveals two clones with distinct gene expression pattern.","authors":"Maria Dampmann, Artur Kibler, Julia von Tresckow, Hans Christian Reinhardt, Ralf Küppers, Bettina Budeus","doi":"10.1080/10428194.2024.2438804","DOIUrl":"10.1080/10428194.2024.2438804","url":null,"abstract":"<p><p>Dual productive B-cell receptor (BCR) rearrangements have been repeatedly reported for chronic lymphocytic leukemia (CLL), but the standard population-based PCR analyses cannot distinguish whether these are bi-clonal CLL, or a monoclonal CLL with bi-allelic productive rearrangements. We investigated CLL cells by combined single-cell RNA and BCR sequencing. We identified two CLL clones using different immunoglobulin (Ig) heavy-chain V region genes (IGHV) genes and distinct Ig λ light chains. One clone is classified as Ig unmutated the other as mutated. The two CLL clones have distinct transcriptomes: Numerous genes were differentially expressed, with genes typical for unmutated or mutated CLL showing the expected representation in the two clones. Using PCR, cloning and Sanger sequencing of the IGHV rearrangements we detected both CLL clones over a period of three years without clinical progression of the CLL and thus giving insights into the disease biology of multi-clonal CLL.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"744-752"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847000","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}
Leukemia & LymphomaPub Date : 2025-04-01Epub Date: 2025-01-16DOI: 10.1080/10428194.2024.2443017
Steven Tessier, Kristen B McCullough, Naseema Gangat, Kebede H Begna, Antoine N Saliba, Abhishek A Mangoankar, Mithun V Shah, William J Hogan, Mrinal M Patnaik, Aref Al-Kali, Hassan B Alkhateeb
{"title":"Venetoclax in combination with fludarabine, cytarabine, granulocyte colony stimulating factor, and idarubicin (FLAG-Ida) in patients with acute leukemia of ambiguous lineage and acute lymphoblastic leukemia.","authors":"Steven Tessier, Kristen B McCullough, Naseema Gangat, Kebede H Begna, Antoine N Saliba, Abhishek A Mangoankar, Mithun V Shah, William J Hogan, Mrinal M Patnaik, Aref Al-Kali, Hassan B Alkhateeb","doi":"10.1080/10428194.2024.2443017","DOIUrl":"10.1080/10428194.2024.2443017","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"780-784"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007809","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}
Leukemia & LymphomaPub Date : 2025-04-01Epub Date: 2024-12-09DOI: 10.1080/10428194.2024.2438801
Ifeyinwa E Obiorah, Debamita Kundu, Folashade Adekunle, Patcharin Pramoonjago, Katherine R Calvo, Paul Liu, Adam Goldfarb
{"title":"Megakaryocyte centrosomal and Golgi structural perturbations in patients with primary myelofibrosis and with <i>RUNX1</i> germline mutation.","authors":"Ifeyinwa E Obiorah, Debamita Kundu, Folashade Adekunle, Patcharin Pramoonjago, Katherine R Calvo, Paul Liu, Adam Goldfarb","doi":"10.1080/10428194.2024.2438801","DOIUrl":"10.1080/10428194.2024.2438801","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"797-800"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801238","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}
Leukemia & LymphomaPub Date : 2025-04-01Epub Date: 2024-12-11DOI: 10.1080/10428194.2024.2438805
Evgenii Shumilov, Lena Levien, Paolo Mazzeo, Wolfram Jung, Andreas Leha, Raphael Koch, Justin Hasenkamp, Gerald Wulf
{"title":"Allogeneic stem cell transplantation against aggressive lymphomas: graft-versus-lymphoma effects in peripheral T-cell lymphoma and diffuse large B-cell lymphoma after myeloablative conditioning.","authors":"Evgenii Shumilov, Lena Levien, Paolo Mazzeo, Wolfram Jung, Andreas Leha, Raphael Koch, Justin Hasenkamp, Gerald Wulf","doi":"10.1080/10428194.2024.2438805","DOIUrl":"10.1080/10428194.2024.2438805","url":null,"abstract":"<p><p>Allogeneic stem cell transplantation (alloSCT) represents a curative option for patients with relapsed/refractory (r/r) aggressive lymphomas. We compared outcomes of alloSCT in r/r PTCL and r/r DLBCL pts (<i>n</i> = 150) who underwent identical myeloablative conditioning chemotherapy, GvHD prophylaxis, and relapse management. 5-year PFS and OS were significantly superior in PTCL compared to DLBCL (56% vs. 24%; 56% vs. 28%; <i>p</i> ≤ 0.005). A landmark analysis (day≥ +100 post-alloSCT) markedly favored outcomes in PTCL vs. DLBCL: 5-year PFS and OS of 76% vs. 30% and 76% and 35%, respectively (<i>p</i> ≤ 0.003). Non-relapse mortality was comparable (35% PTCL vs. 34% DLBCL, <i>p</i> = 0.894), whereas post-alloSCT relapse mortality was significantly higher in DLBCL (36% vs. 10%, <i>p</i> = 0.0007). The occurence of limited chronic GvHD did not improve outcomes in DLBCL, whereas extensive chronic GvHD was a negative risk factor for both (HR 2.09 and 2.80, <i>p</i> ≤ 0.006). In conclusion, we gained evidence for strong graft-versus-lymphoma activity against PTCL but not DLBCL.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"668-679"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807379","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}
Leukemia & LymphomaPub Date : 2025-04-01Epub Date: 2024-12-17DOI: 10.1080/10428194.2024.2441875
Chie Ishikawa, Naoki Mori
{"title":"ML385, a selective inhibitor of Nrf2, demonstrates efficacy in the treatment of adult T-cell leukemia.","authors":"Chie Ishikawa, Naoki Mori","doi":"10.1080/10428194.2024.2441875","DOIUrl":"10.1080/10428194.2024.2441875","url":null,"abstract":"<p><p>Nrf2 plays a critical role in regulating cytoprotective transcriptional responses and glucose metabolism while also preventing inflammation-induced carcinogenesis. However, Nrf2 can paradoxically promote carcinogenesis. Here, we aimed to elucidate the role of Nrf2 in ATL associated with HTLV-1. HTLV-1-infected T-cell lines exhibited nuclear accumulation of Nrf2. Nrf2 knockdown along with the inhibition of its activity using ML385, decreased cell proliferation and survival. Furthermore, ML385-induced G1 arrest by enhancing γH2AX and p53 expression while downregulating CDK4/6, cyclin D2/E, and c-Myc. Additionally, ML385 triggered caspase-mediated apoptosis by downregulating the expression of anti-apoptotic proteins while upregulating pro-apoptotic proteins. The compound also induced necroptosis, promoted JNK phosphorylation, and inhibited the NF-κB, AP-1, and STAT3/5 signaling. Moreover, ML385 was found to reduce the expression of LDHA, glucose uptake, and the levels of lactate derived from glycolysis. Overall, these results suggest that Nrf2 functions as an oncogene in ATL and may represent a promising therapeutic target.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":" ","pages":"721-732"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846998","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}