{"title":"Incidence, Risk Factors, and Outcomes of Viral Reactivations in Alternative Donor Hematopoietic Stem Cell Transplants.","authors":"Anant Gokarn, Vinodhini Murugaiyan, Sachin Punatar, Sumeet Mirgh, Akanksha Chichra, Nishant Jindal, Avinash Bonda, Lingaraj Nayak, Bhausaheb Bagal, Gaurav Bain, Vivek Bhat, Sanjay Biswas, Sadhana Kannan, Rachana Tripathi, Shesheer Kumar, Navin Khattry","doi":"10.31547/bct-2025-011","DOIUrl":"10.31547/bct-2025-011","url":null,"abstract":"<p><strong>Background: </strong>Viral reactivations frequently complicate unrelated donor (UD) and haploidentical (HI) stem cell transplants (SCTs). We analyzed incidence, risk factors, and outcomes of viral reactivations in alternative donor transplants at our center.</p><p><strong>Methods: </strong>This retrospective study included all cases of UD or HI transplants performed between January 1, 2009 and February 29, 2020. We identified 196 viral reactivations in 87 patients in this cohort.</p><p><strong>Results: </strong>The incidence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) reactivation was 80.5, 36.7, and 26%, respectively. CMV colitis was observed in six patients (8.5%). Acute graft-versus-host disease (GVHD) was a significant risk factor for CMV reactivation. Four patients (5%) developed ADV disease requiring treatment with cidofovir. Anti-thymocyte globulin use and acute GVHD were significant risk factors for ADV reactivation. Mild hemorrhagic cystitis due to BK virus was observed in 32% patients. However, significant cystitis requiring intervention was seen in only four patients. Two patients developed EBV-related lymphoproliferative disorder and one patient experienced human herpes virus 6-related graft failure. Viral reactivations had no impact on overall survival.</p><p><strong>Conclusions: </strong>The incidence of CMV reactivation in alternative donor HSCTs is high (80%) in the Indian population. Acute GVHD is a significant risk factor for CMV, ADV, or EBV reactivation. The rates of ADV, BK virus, and EBV reactivation requiring intervention are low. Better prophylactic strategies are required to prevent CMV reactivation in alternative donor transplants.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 4","pages":"290-300"},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reduced-versus Standard-dose Melphalan as Single-agent Conditioning Regimen in Auto HSCT for Multiple Myeloma: A Systematic Review and Meta-Analysis.","authors":"Rowel David D Yap, Deonne Thaddeus Gauiran","doi":"10.31547/bct-2025-008","DOIUrl":"10.31547/bct-2025-008","url":null,"abstract":"<p><strong>Background: </strong>The optimal conditioning dose of melphalan for autologous hematopoietic stem cell transplantation (AHSCT) in multiple myeloma remains a subject of debate. While prior studies have presented conflicting evidence on whether standard-dose melphalan (SDM, 200 mg/m<sup>2</sup>) provides a statistically significant survival advantage over reduced-dose melphalan (RDM, 140 mg/m<sup>2</sup>), further investigation is necessary to clarify this.</p><p><strong>Aim: </strong>This systematic review and meta-analysis aimed to consolidate existing studies and assess whether standard-dose melphalan confers a significant benefit in terms of overall survival (OS) and progression-free survival (PFS) compared to reduced-dose melphalan, while also evaluating secondary outcomes non-relapse mortality (NRM), transplant-related mortality (TRM), and engraftment time (ET).</p><p><strong>Methods: </strong>A comprehensive literature search across four electronic databases (i.e., The Cochrane, ClinicalTrials.gov, PubMed, Google Scholar) identified six eligible studies published in the last 10 years, with a pooled sample size of 3,721 patients. The meta-analysis was conducted for the primary outcomes (OS and PFS) using hazard ratios (HRs) and their 95% confidence intervals (CIs), with effect sizes calculated based on reported <i>p</i>-values, population sizes, and Cohen's framework for effect size estimation. A fixed-effects model was employed, assuming relative homogeneity of effect sizes across studies.</p><p><strong>Results: </strong>For overall survival, no significant difference was seen between standard-dose and reduced-dose melphalan (95% CI: -0.025 to 0.217, <i>p</i>=0.119). Similarly, no significant difference in PFS was observed (95% CI: -0.021 to 0.088, <i>p</i>=0.353). The effect sizes for OS (0.0962) and PFS (0.0337) were small, indicating little clinical relevance despite trends to advantages in OS (16.9 months) and PFS (2.3 months) for the standard-dose group. The systematic review of secondary outcomes (NRM, TRM, and ET) demonstrated no significant differences between the two dose groups. Heterogeneity for primary outcomes was low (OS: I<sup>2</sup> = 27.36%, <i>p</i>=0.316; PFS: I<sup>2</sup> = 0.03%, <i>p</i>=0.567).</p><p><strong>Conclusions: </strong>Although standard-dose melphalan shows better survival trends, statistical analysis shows no significant difference in overall or progression-free survival. The small effect sizes also suggest these differences are not clinically meaningful. Due to lack of clear survival benefit between SDM and RDM, choice should be based on other important patient factors like risk of side effects and ability to tolerate treatment.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 4","pages":"301-310"},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood cell therapyPub Date : 2025-11-07eCollection Date: 2025-11-25DOI: 10.31547/bct-2025-006
Kumar Nikhil M, Nathany Shrinidhi, Swaminathan Anusha, Yadav Chitresh, Panda Rastogi Neha, Dua Vikas, Bhargava Rahul
{"title":"Response to Cyclosporine & Eltrombopag in Primary Graft Failure after Autologous transplant in Myeloma.","authors":"Kumar Nikhil M, Nathany Shrinidhi, Swaminathan Anusha, Yadav Chitresh, Panda Rastogi Neha, Dua Vikas, Bhargava Rahul","doi":"10.31547/bct-2025-006","DOIUrl":"10.31547/bct-2025-006","url":null,"abstract":"<p><p>Primary graft failure is an uncommon but serious complication that occurs when the hematopoietic engraftment fails to occur within the expected timeframe. Here, we report the case of a 63-year-old female with multiple myeloma who developed primary graft failure after Autologous stem cell transplant (ASCT). Despite initial concerns regarding his poor prognosis, the patient was successfully treated with cyclosporine as a novel rescue therapy. This condition necessitates prolonged hospitalization, frequent transfusions, and poses a high risk of life-threatening infections due to persistent cytopenias. The incidence of primary graft failure in myeloma patients undergoing ASCT has been reported to be less than 1% in recent studies. Despite its low occurrence, the clinical consequences of this complication are profound, contributing significantly to morbidity and mortality in this patient population. Cyclosporine has emerged as a promising therapeutic agent for the management of primary graft failure. The mechanism of action is believed to involve immunosuppression. This case underscores the potential utility of cyclosporine as a therapeutic option in patients with primary graft failure following ASCT, offering an alternative to the more invasive and risky strategy of allogeneic stem cell transplant.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 4","pages":"286-289"},"PeriodicalIF":0.0,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bone marrow transplantation for leukocyte adhesion deficiency type III: immunosuppressant dosage adjustments against severe T-cell mixed chimerism.","authors":"Takashi Koike, Eri Shigematsu, Keisuke Otsubo, Shigeki Ochiai, Yoshifumi Fukuda, Hidefumi Hiramatsu, Hiromasa Yabe","doi":"10.31547/bct-2025-003","DOIUrl":"10.31547/bct-2025-003","url":null,"abstract":"<p><p>Allogeneic stem cell transplantation from an HLA-mismatched unrelated donor was performed for a patient with leukocyte adhesion deficiency type III with a myeloablative regimen including full-dose busulfan. Mixed chimerism with donor-derived T cells at less than 10% was observed within 4 weeks after transplantation. Repeated cycles of discontinuation and resumption of tacrolimus early after transplantation were performed with the aim of reversing the recipient-dominant T-cell chimerism. Specifically, tacrolimus was quickly tapered on day 15 and discontinued on day 20 when the recipient's chimerism increased, and resumed upon the observation of early signs of acute graft-versus-host disease, such as fever and skin rash, on day 24. This process was repeated from day 30 to day 44. All subsets, including granulocytes, T cells, and natural killer cells, attained donor chimerism of more than 90% on day 42 after transplantation and 100% at day 82 and beyond. Immunosuppressant dosage adjustments may be a treatment option for mixed chimerism after stem cell transplantation.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 4","pages":"281-285"},"PeriodicalIF":0.0,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adult-Onset Epstein-Barr Virus-Associated T-Cell Lymphoproliferative Disease with Central Nervous System Involvement.","authors":"Atsushi Wada, Hiro Tatetsu, Shinya Endo, Taichi Hirano, Nao Nishimura, Kenji Tokunaga, Takafumi Shichijo, Yusuke Higuchi, Takahisa Nakamura, Mikiko Izaki, Kenichiro Eto, Yumi Honda, Ken-Ichi Iyama, Kisato Nosaka, Kennosuke Karube, Yoshiki Mikami, Jun-Ichirou Yasunaga","doi":"10.31547/bct-2025-009","DOIUrl":"10.31547/bct-2025-009","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disease (EBV+ T-cell LPD), including chronic active Epstein-Barr virus (CAEBV) disease, can affect the central nervous system (CNS) in children, albeit rarely reported in adults. We report a case of an adult with EBV+ T-cell LPD and CNS involvement treated with haploidentical stem cell transplantation (haplo-SCT) and post-transplant cyclophosphamide (PTCy). A 59-year-old woman developed a high fever and elevated lactate dehydrogenase (LDH) levels. Based on the clinical course, high serum EBV-DNA levels, and the presence of EBV-infected T cells in her bone marrow, she was diagnosed with EBV+ T-cell LPD. The patient initially responded to cooling therapy and chemotherapy, leading to a marked decrease in EBV-DNA levels. Subsequently, she experienced a relapse in the CNS, as evidenced by elevated EBV-DNA levels in the cerebrospinal fluid. After chemotherapy and whole-brain irradiation, the patient underwent haplo-SCT with PTCy, following reduced-intensity conditioning. The EBV-DNA load was undetectable 27 days after haplo-SCT, and MRI findings showed no apparent residual disease. This case highlights the importance of considering CNS relapse despite apparent virologic response in adult-onset EBV+ T-cell LPD. To our knowledge, this is among the few reported adult cases with clinically diagnosed CNS involvement successfully treated with allogeneic SCT.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 4","pages":"274-280"},"PeriodicalIF":0.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Successful Neutrophil Engraftment with Continued Ruxolitinib in Cord Blood Transplantation.","authors":"Tomohiro Nagano, Takumi Kondo, Ryuichiro Hiyama, Daisuke Ikeda, Kenta Hayashino, Yusuke Inoue, Masaya Ueno, Yayoi Ueda, Saya Kubota, Hiroki Kobayashi, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda","doi":"10.31547/bct-2025-012","DOIUrl":"10.31547/bct-2025-012","url":null,"abstract":"<p><p>The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is crucial for immune function and hematopoiesis, which partly explains why cytopenia is a major adverse effect of ruxolitinib, a selective JAK1/2 inhibitor. Hematologic toxicity restricts the use of ruxolitinib during the pre-engraftment phase of allogeneic hematopoietic stem cell transplantation for myelofibrosis and graft-versus-host disease (GVHD) prophylaxis. While some reports have described its use in peripheral blood and bone marrow transplantation, its application in cord blood transplantation (CBT) remains unknown. Herein, we report two cases of CBT in which ruxolitinib was administered to treat GVHD after prior allogeneic transplantation. In Case 1, a patient underwent a third transplant for acute myeloid leukemia, and in Case 2, a patient received CBT for post-transplant lymphoproliferative disorder following transplantation for classic Hodgkin lymphoma. Neutrophil engraftment was achieved in both cases, and Case 2 developed a pre-engraftment immune reaction. Platelet and red blood cell engraftment did not occur in either case, likely due to underlying comorbidities or limited survival, rather than the effects of ruxolitinib. This is the first report documenting successful neutrophil engraftment in CBT with concurrent ruxolitinib administration, suggesting its potential feasibility during the pre-engraftment phase. Further studies are warranted to evaluate its effects on multilineage hematopoietic recovery, infections, GVHD, and relapse risk.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 4","pages":"268-273"},"PeriodicalIF":0.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Feasibility of early tacrolimus initiation in haploidentical-PBSCT with post-transplant cyclophosphamide after melphalan-based conditioning regimen.","authors":"Wataru Kitamura, Toshiki Terao, Ken-Ichi Matsuoka, Takumi Kondo, Keisuke Seike, Keiko Fujii, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Nobuharu Fujii, Yoshinobu Maeda","doi":"10.31547/bct-2025-013","DOIUrl":"10.31547/bct-2025-013","url":null,"abstract":"<p><p>In haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide (PTCy-haplo), early initiation of calcineurin inhibitors may affect transplant outcome by inducing CD8<sup>+</sup> transient exhaustion-like T cells which are important for chronic graft-versus-host disease and graft-versus-leukemia/lymphoma effects based on a murine model. However, to our best knowledge, there has been no report about modification of fludarabine (Flu)/melphalan (Mel)-based PTCy-haplo in a real-world setting. To evaluate the impact of early tacrolimus (TAC) initiation on outcomes, we retrospectively analyzed 19 patients at our institution between April 2017 and March 2024. The incidence and grade of cytokine release syndrome (CRS) were low (31.6% and all grades ≤ 2). In addition, despite the poor baseline characteristics including older age (median, 59 years [range, 25-72]), active diseases at the time of PTCy-haplo (n=8), and short interval between the first and second allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n=8; median, 12.4 months [range, 3.9-32.9]; all patients received Flu/busulfan (Bu)-based conditioning regimen for their first allo-HSCT), only two patients (10.5%) developed sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD). With a median follow-up of 30.2 months (range, 1.0-53.1), overall survival and disease-free at 2 years were 56.8 and 51.5%, respectively. These findings suggested that early TAC initiation using Flu/Mel-based PTCy-haplo may be potentially useful for older patients with low tolerance to CRS, high risk of SOS/VOD or recurrence, or for those who are unlikely to receive Bu-based conditioning regimen due to early relapse after allo-HSCT with Bu-based conditioning regimen.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 4","pages":"262-267"},"PeriodicalIF":0.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood cell therapyPub Date : 2025-10-03eCollection Date: 2025-11-25DOI: 10.31547/bct-2025-005
Abeer Yaseen, Anas Zayed, Mona Ribie, Albatol Alamoush, Yazan Talab, Lina Marie, Waleed Da'na, Omar Shahin, Khalid Halahleh, Kamal Al-Rabie, Mohammad Ma'koseh, Zaid H Abdel Rahman
{"title":"Therapy-related Myeloid Neoplasms After Autologous Stem Cell Transplantation for Lymphoma: A Single-Center Experience.","authors":"Abeer Yaseen, Anas Zayed, Mona Ribie, Albatol Alamoush, Yazan Talab, Lina Marie, Waleed Da'na, Omar Shahin, Khalid Halahleh, Kamal Al-Rabie, Mohammad Ma'koseh, Zaid H Abdel Rahman","doi":"10.31547/bct-2025-005","DOIUrl":"10.31547/bct-2025-005","url":null,"abstract":"<p><p>Despite advances in lymphoma treatment, autologous hematopoietic stem cell transplantation (auto-HCT) remains essential in regions with limited access to novel therapies. Improved survival post-auto-HCT has led to an increased incidence of therapy-related myeloid neoplasms (t-MN). We conducted a retrospective analysis of adult patients (≥18 years) who underwent auto-HCT for lymphoma at King Hussein Cancer Center in Jordan between 2003 and 2020 with the goal of evaluating characteristics and outcomes of patients developing t-MN post-auto-HCT. We identified 407 patients with a median follow-up of 5.8 years. The median age at auto-HCT was 34.6 years, 54.9% were males, 65.3% had Hodgkin lymphoma, and 41.1% were refractory to first-line treatment. dexamethasone, ara-C, cisplatin (DHAP) was the most common salvage regimen (47.8%). At the time of auto-HCT, 39.7% were in complete remission. BCNU, etoposide, ara-C, melphalan (BEAM) was the most common conditioning regimen 91.9%. The 5-year overall survival (OS) was 64.4%. Thirteen patients (3.2%) developed t-MN (5 acute myeloid leukemia, 8 myelodysplastic syndrome) with a median onset of 3.25 years post-auto-HCT. The median OS post t-MN diagnosis was 6 months. Patients with t-MN were older (<i>p</i> < 0.001), more likely to have non-Hodgkin lymphoma (<i>p</i>=0.023) and had more comorbidities (<i>p</i>=0.02). The most common cytogenetic abnormality was del (7) (46%), and <i>TP53</i> was the most common molecular abnormality (15%). Age at transplant was the only significant predictor of t-MN (Hazard Ratio=1.162, <i>p</i> < 0.001) on multivariate analysis. t-MM accounted for 18.8% of non-relapse mortality (NRM). t-MN significantly contributes to NRM post-auto-HCT. Age at transplant is the primary risk factor, highlighting the need for vigilant monitoring and risk mitigation strategies.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 4","pages":"252-261"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effective and safe administration of Epcoritamab in relapsed CD19-CD5+ DLBCL following CAR-T therapy.","authors":"Takashi Shimakawa, Noriaki Kawano, Yuichiro Semba, Yasuo Mori, Ken Takigawa, Takuji Yamauchi, Kohta Miyawaki, Fumiaki Jinnouchi, Teppei Sakoda, Kyohei Mori, Masatoshi Shimo, Masahiro Otsu, Riichiro Ikeda, Shunya Shiraishi, Takashi Nakaike, Kiyoshi Yamashita, Koichi Mashiba, Ikuo Kikuchi, Kousuke Marutsuka, Koichi Ohshima, Sawako Matsuzaki, Kennosuke Karube, Koji Kato, Takahiro Maeda, Koichi Akashi","doi":"10.31547/bct-2024-037","DOIUrl":"10.31547/bct-2024-037","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment landscape for relapsed or refractory non-Hodgkin lymphoma, achieving a 5-year overall survival rate of 40-50%. However, relapse remains a major challenge, especially due to CD19-negative clones. Epcoritamab, a bispecific antibody targeting CD20 and CD3, offers a potential solution for post-CAR-T relapse; however, clinical data in this setting remain limited, particularly in Japan.</p><p><strong>The case: </strong>A 68-year-old woman with CD5-positive diffuse large B-cell lymphoma (DLBCL) relapsed multiple times following various treatments, including CAR-T therapy. Genetic profiling revealed a <i>MYD88/CD79B</i>-mutated (MCD) subtype with CD19-negative clones resistant to CAR-T cells. Given her high tumor burden, she received debulking therapy followed by epcoritamab treatment. Despite concerns about tumor lysis syndrome, cytokine release syndrome, and neurotoxicity, no significant adverse events occurred. The patient achieved a complete remission, demonstrating the efficacy and safety of this approach.</p><p><strong>Conclusion: </strong>This case highlights the potential of epcoritamab combined with debulking therapy for treating CAR-T-refractory CD19-negative DLBCL. This is the first validated case in Japan showing that epcoritamab is a viable and safe treatment option for post-CAR-T relapse, addressing a critical unmet need in the current therapeutic landscape.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 3","pages":"244-249"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Composite Measurable Residual Disease Assessment with PET-CT and flow cytometry in Multiple Myeloma patients undergoing Autologous Transplant.","authors":"Rudra Narayan Swain, Arihant Jain, Sarthak Wadhera, Aditya Jandial, Charanpreet Singh, Deepesh Lad, Gaurav Prakash, Alka Khadwal, Sreejesh Sreedharuni, Man Updesh Singh Sachdeva, Rajendra Kumar Basher, Reena Das, Pankaj Malhotra","doi":"10.31547/bct-2025-002","DOIUrl":"10.31547/bct-2025-002","url":null,"abstract":"<p><strong>Background: </strong>Bone marrow (BM) Measurable Residual Disease (MRD) assessments underestimate disease burden in multiple myeloma, as focal lesions can exist outside the marrow. Functional imaging, like positron emission tomography-computed tomography (PET-CT), offers valuable insights into residual disease beyond the marrow. Combining marrow flow cytometry (FCM) with PET-CT for a composite MRD (cMRD) assessment before and after autologous stem cell transplant (ASCT) is expected to provide prognostic information, particularly in settings where patients receive extended duration of anti-myeloma therapy prior to ASCT.</p><p><strong>Methods: </strong>In this retrospective cohort study, we evaluated the prognostic impact of cMRD in newly diagnosed multiple myeloma (NDMM) patients who underwent triplet/quadruplet-based induction followed by ASCT from January 2017 to June 2023. cMRD was assessed before ASCT and again around day 100 post-transplant. cMRD negativity was defined as undetectable residual clonal plasma cells (sensitivity 1×10<sup>-5</sup>) on multi coloured FCM and PET-CT negativity per The International Myeloma Working Group criteria.</p><p><strong>Results: </strong>Among 106 patients undergoing ASCT, 82 had cMRD assessments before and on day 100 post-ASCT. Median pre-ASCT treatment duration was 11 months (interquartile range [IQR]: 4-18). At the pre-ASCT time point, sixty seven percent patients were bone marrow MRD negative (BM-MRD<sup>PRE-</sup>), while 38% were PET-CT negative (PET<sup>PRE-</sup>). Post-ASCT, these rates were 74% (BM-MRD<sup>POST-</sup>) and 49% (PET-CT<sup>POST-</sup>) respectively. At a median follow-up of 35 months (IQR: 23.5-58), median time to next treatment (TTNT) and overall survival (OS) were not reached. At three years, TTNT was significantly higher in patients who were cMRD-negative before ASCT compared to those who were cMRD-positive [91% (confidence interval (CI): 77-100) versus 67% (CI: 52-80); <i>p</i>=0.027]. BM-MRD<sup>PRE-</sup> and PET<sup>PRE-</sup> were both independently associated with improved TTNT on univariate analysis [Hazard Ratio: 0.32 (0.14-0.74) and 0.45 (0.23-0.94) respectively]. Post-ASCT cMRD status did not significantly impact TTNT [82% (CI: 68-96) versus 65% (CI: 51-69); <i>p</i>=0.116]. Three-year TTNT rates were similar among patients with and without baseline high-risk cytogenetic abnormalities (HRCA) if they maintained sequential cMRD negativity. In multivariate analysis, the absence of HRCA, complete response before ASCT, cMRD<sup>PRE-</sup>, and sustained cMRD negativity at both time points were independent predictors of longer TTNT.</p><p><strong>Conclusions: </strong>Pre-ASCT cMRD assessment using both PET-CT and bone marrow FCM provides prognostic value in NDMM. This approach is particularly relevant in real-world settings where patients often receive prolonged induction therapy before ASCT.</p>","PeriodicalId":72423,"journal":{"name":"Blood cell therapy","volume":"8 3","pages":"234-243"},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}