Blood ResearchPub Date : 2026-04-22DOI: 10.1007/s44313-026-00137-2
Jeong Suk Koh, Wonhyoung Seo, Sora Kang, Myung-Won Lee, Hyewon Ryu, Seung-Woo Baek, Ik-Chan Song, Hyo-Jin Lee, Deog-Yeon Jo
{"title":"Monitoring of JAK2V617F allele burden in patients with essential thrombocythemia.","authors":"Jeong Suk Koh, Wonhyoung Seo, Sora Kang, Myung-Won Lee, Hyewon Ryu, Seung-Woo Baek, Ik-Chan Song, Hyo-Jin Lee, Deog-Yeon Jo","doi":"10.1007/s44313-026-00137-2","DOIUrl":"10.1007/s44313-026-00137-2","url":null,"abstract":"<p><strong>Background/aim: </strong>This study retrospectively examined the clinical implications of monitoring JAK2V617F, with a particular focus on disease transformation, in a Korean population of patients with essential thrombocythemia (ET).</p><p><strong>Methods: </strong>Medical records of patients diagnosed with ET between January 1996 and December 2021 at Chungnam National University Hospital, Daejeon, Korea, were reviewed. Both episodic changes (increase or decrease) and longitudinal patterns of change (stable, gradual increase, or gradual decrease) in JAK2V617F variant allele frequency (VAF), measured at 1-year intervals, were analyzed.</p><p><strong>Results: </strong>Among the 87 patients who had JAK2V617F VAF measured at least three times, 23 (26.4%), 21 (24.1%), and 16 (18.4%) experienced increases of ≥ 25%, ≥ 50%, and ≥ 100%, respectively, while 27 (42.5%), 26 (29.9%), and 2 (2.3%) experienced decreases of ≥ 25%, ≥ 50%, and 100%, respectively. Patients with VAF increases had significantly poorer transformation-free survival than those without increases (15-year survival for ≥ 50% increase: 79.2% vs. 97.5%; p = 0.007). Regarding the longitudinal patterns, 62 (71.3%), 13 (14.9%), and 12 (13.8%) patients were classified as having stable, gradual increase, and gradual decrease patterns, respectively. Transformation-free survival was worse in patients with a gradual increase and better in those with a gradual decrease than in those with a stable pattern (20-year survival: 100% vs. 88.8% vs. 31.3%; p = 0.026).</p><p><strong>Conclusions: </strong>An increasing JAK2V617F allele burden over time is associated with disease transformation in ET, supporting the need for the ongoing monitoring of JAK2V617F VAF in these patients.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147785115","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 ResearchPub Date : 2026-04-22DOI: 10.1007/s44313-026-00136-3
Alfadil Haroon, Hazzaa Alzahrani, Mostafa F Mohammed Saleh, Ali Aalahmari, Shaykhah Alotaibi, Tusneem Elhassan, Feras Alfraih, Fahad Alsharif, Syed O Ahmed, Fahad Almohareb, Riad El Fakih, Mahmoud Aljurf
{"title":"Prognostic significance of PNH clones in aplastic anemia treated with immunosuppression or allogeneic HSCT: a 20-year single-center experience.","authors":"Alfadil Haroon, Hazzaa Alzahrani, Mostafa F Mohammed Saleh, Ali Aalahmari, Shaykhah Alotaibi, Tusneem Elhassan, Feras Alfraih, Fahad Alsharif, Syed O Ahmed, Fahad Almohareb, Riad El Fakih, Mahmoud Aljurf","doi":"10.1007/s44313-026-00136-3","DOIUrl":"10.1007/s44313-026-00136-3","url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal nocturnal hemoglobinuria (PNH) clones are detected in up to 60% of patients with aplastic anemia (AA); however, their prognostic impact remains incompletely defined, particularly in the context of frontline immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (HSCT).</p><p><strong>Methods: </strong>We retrospectively analyzed 207 patients with AA treated between 2004 and 2024 at a single institution. PNH clones were identified at diagnosis in 64 patients (30.9%). Treatment modalities included IST (n = 104) and HSCT (n = 103). Clinical outcomes, including overall survival (OS), event-free survival, graft-versus-host disease (GVHD), relapse, and non-relapse mortality, were compared between the PNH-positive and PNH-negative cohorts.</p><p><strong>Results: </strong>At 5 years, PNH-positive patients treated with IST had significantly improved OS compared with PNH-negative patients (100% vs. 72.4%, p = 0.004). In the HSCT group, OS was 100% in PNH-positive patients versus 90% in PNH-negative patients (p = 0.09). The incidence of chronic GVHD after HSCT was significantly lower in the PNH-positive group (4% vs. 27%, p = 0.01), whereas the rates of acute GVHD, graft failure, and relapse were comparable. Clone size (small vs. large) did not affect survival or GVHD outcomes.</p><p><strong>Conclusions: </strong>The presence of a PNH clone in AA was associated with superior survival following IST and a lower incidence of chronic GVHD following HSCT. These findings suggest that PNH positivity may serve as a prognostic and immunomodulatory biomarker in AA and support its integration into therapeutic decision-making and risk stratification algorithms.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147785222","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":"Targeting the HERV-K102 envelope elicits pyroptosis and represents a novel therapeutic strategy for acute myeloid leukemia.","authors":"Lihong Zong, Qian Luo, Jingru Zhao, Huyi Lei, Hui Liu, Mengyuan Li, Yiyuan Chen, Minghuan Zhang, Rongzhen Xu, Wenbin Qian","doi":"10.1007/s44313-026-00134-5","DOIUrl":"10.1007/s44313-026-00134-5","url":null,"abstract":"<p><strong>Objective: </strong>Several recent studies have focused on human endogenous retroviruses (HERVs). HERVs entered the human genome millions of years ago and are associated with various diseases including cancer and immune regulation. Among these, the HERV-K family exhibits the highest transcriptional activity. However, little is known about the expression of HERVs in acute myeloid leukemia (AML) and their potential as biomarkers or therapeutic targets. This study primarily investigated the role of HERV-K102 in AML development and explored the underlying mechanisms.</p><p><strong>Methods: </strong>The expression profiles of HERV K102 in AML and normal samples were analyzed using The Cancer Genome Atlas (TCGA) database and AML cell lines. Knockout models were generated using CRISPR-Cas9-mediated deletion of the HERV-K102 envelope (K-Env). Cell viability and pyroptosis rates were measured using the MTT assay and flow cytometry, respectively. Transcriptome analysis was performed to identify differentially expressed genes and related pathways. Pyroptosis markers were detected using qRT-PCR and western blotting. The role of HERV-K102 in AML was validated using an inducible knockout xenograft tumor model.</p><p><strong>Results: </strong>HERV-K102 was aberrantly activated and highly expressed in AML cells. K-Env depletion inhibited AML cell proliferation and promoted apoptosis. Furthermore, K-Env knockout induced pyroptosis, as indicated by increased lactate dehydrogenase (LDH) release and enhanced cleavage of caspase-1 and gasdermin D (GSDMD). Transcriptomic and functional analyses demonstrated that this process is mediated by S100A9 upregulation and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome pathway.</p><p><strong>Conclusion: </strong>Our findings suggest that HERV-K102 Env may play an important role in AML pathogenesis and represents a novel diagnostic and therapeutic target.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677640","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":"Autologous bone marrow transplantation in non-Hodgkin lymphoma patients following different conditioning regimens: an 11-year single-center quasi-experimental study.","authors":"Sahar Tavakoli Shiraji, Mohammad Biglari, Soroush Rad, Maryam Barkhordar, Hossein Kamranzadeh Foumani, Ghasem Janbabaei, Seied Asadollah Mousavi, Mohammad Vaezi, Kamran Mohammadi, Ardeshir Ghavamzadeh","doi":"10.1007/s44313-026-00131-8","DOIUrl":"10.1007/s44313-026-00131-8","url":null,"abstract":"<p><strong>Purpose: </strong>Non-Hodgkin lymphoma (NHL) constitutes 90% of all lymphomas and accounts for 2.8% of new cancer cases and 2.6% of cancer-related deaths in 2020. Hematopoietic stem cell transplantation remains the standard treatment for refractory or relapsed NHL. Due to the shortage of carmustine, this study aimed to compare the outcomes of patients undergoing autologous stem cell transplantation (ASCT) with conditioning regimens that either include or exclude this drug over an 11-year period.</p><p><strong>Methods: </strong>This retrospective study included a cohort of 240 patients with NHL who underwent ASCT with an EAM conditioning regimen, both with and without carboplatin. Following informed consent, clinical data from patients who underwent transplantation between March 2006 and May 2017 were collected. Patients were followed to assess overall survival (OS) and disease-free survival (DFS) as primary endpoints.</p><p><strong>Results: </strong>No significant differences were observed between the survival outcomes of the two groups with differing conditioning regimens (P = 0.27 for OS; P = 0.49 for DFS). The 3-year and 5-year OS rates were 81% and 74.8%, respectively, with a median follow-up of 74 months. The 3-year and 5-year DFS rates were 66.6% and 62.1%, respectively. OS and DFS were significantly higher in patients with B-cell lymphomas compared to those with T-cell lymphoma (P < 0.01).</p><p><strong>Conclusion: </strong>Our real-world data indicate that the addition of carboplatin to the EAM conditioning regimen does not significantly affect survival outcomes for patients with NHL undergoing ASCT.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639939","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 ResearchPub Date : 2026-04-06DOI: 10.1007/s44313-026-00132-7
Yehyun Kang, Hyeonah Lee, Yu Jin Park, Seung-Tae Lee, Jong Rak Choi, Saeam Shin
{"title":"Comparative evaluation of two NGS-based assays for somatic hypermutation analysis of IGHV genes in chronic lymphocytic leukemia.","authors":"Yehyun Kang, Hyeonah Lee, Yu Jin Park, Seung-Tae Lee, Jong Rak Choi, Saeam Shin","doi":"10.1007/s44313-026-00132-7","DOIUrl":"10.1007/s44313-026-00132-7","url":null,"abstract":"<p><strong>Purpose: </strong>Somatic hypermutation (SHM) of the immunoglobulin heavy chain variable (IGHV) region is a key prognostic marker in chronic lymphocytic leukemia (CLL). Traditionally, SHM status has been determined using Sanger sequencing (SS); however, next-generation sequencing (NGS) provides an alternative method for assessing both SHM status and clonal rearrangements. This study aimed to compare the performance of two commercially available NGS assays for evaluating IGH clonality and SHM status in CLL.</p><p><strong>Methods: </strong>In this retrospective study, 42 samples from patients diagnosed with CLL were analyzed. Genomic DNA extracted from peripheral blood or bone marrow aspirates was analyzed using two commercial NGS assays: the LymphoTrack® IGHV Leader (Leader) and IGH FR1 (FR1) assays (Invivoscribe, CA, USA). SS was performed as the reference method for SHM assessment.</p><p><strong>Results: </strong>The Leader assay identified clonality in 95.2% of cases, whereas the FR1 assay detected clonality in 88.1%. Conclusive SHM status was determined in 90.5% of samples using the Leader assay and in 76.2% using the FR1 assay; when results from both assays were combined, the rate increased to 92.9%. Among samples with conclusive results by both SS and each NGS assay, the Leader assay demonstrated higher concordance with SS (97.1%, 34/35) than the FR1 assay (86.2%, 25/29). Greater variability in clonal detection was observed with the FR1 assay.</p><p><strong>Conclusion: </strong>These findings indicate that the Leader assay provides a more reliable assessment of SHM status, with higher concordance with SS. Although the FR1 assay may offer additional information regarding clonal patterns, its results should be interpreted cautiously. Given the limited sample size, further studies are warranted to validate these findings. Overall, the Leader assay appears to be more suitable as a primary tool for SHM evaluation, with FR1 results serving a complementary role when interpreted in clinical context.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13057106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624126","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":"Letermovir for cytomegalovirus prophylaxis in pediatric allogeneic hematopoietic stem cell transplantation: a single-center experience.","authors":"Pai-Lin Tsai, Meng-Yao Lu, Hsiu-Hao Chang, Yung-Li Yang, Chia-Jui Du, Chang-Hsueh Wu, Shiann-Tarng Jou, Shu-Wei Chou","doi":"10.1007/s44313-026-00133-6","DOIUrl":"10.1007/s44313-026-00133-6","url":null,"abstract":"<p><strong>Purpose: </strong>Letermovir prophylaxis results in a significantly lower risk of clinically significant cytomegalovirus (CMV) infection in adult hematopoietic stem cell transplant recipients. However, studies supporting its efficacy in pediatric patients are limited.</p><p><strong>Methods: </strong>We retrospectively reviewed the outcomes of ten patients who underwent allogeneic hematopoietic stem cell transplantation and received letermovir prophylaxis between November 2021 and October 2024 at our institution.</p><p><strong>Results: </strong>Among the ten patients, six donors were CMV-seropositive, whereas nine recipients were CMV-seropositive. Six patients (60%) underwent transplantation from mismatched unrelated donors, and two (20%) from haploidentical donors. Five patients (50%) developed acute graft-versus-host disease (GvHD) > grade 2. Ten patients received letermovir prophylaxis for a median of 101.5 days (range, 26-279). The median daily letermovir dose was 4.6 mg/kg (range, 3.5-11.1 mg/kg), with concomitant use of cyclosporin in nine patients. Eight patients (80%) received letermovir as primary prophylaxis, and two (20%) received it as secondary prophylaxis. None of the patients treated with letermovir as primary prophylaxis had CMV reactivation even after discontinuation (median follow-up, 154 days after transplantation, range 37-850). Both patients who received letermovir as secondary prophylaxis showed CMV reactivation. None of the patients developed CMV infection. No significant adverse effects resulting from the letermovir treatment were observed.</p><p><strong>Conclusion: </strong>Our data support the feasibility of letermovir prophylaxis in pediatric patients. The optimal dose of letermovir in pediatric patients has not been established. Letermovir, used as secondary prophylaxis in pediatric patients, was well tolerated.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13047026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595351","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 ResearchPub Date : 2026-03-07DOI: 10.1007/s44313-026-00127-4
Hee Young Ju
{"title":"Epstein-Barr virus-associated lymphoma: current understanding and treatment strategies.","authors":"Hee Young Ju","doi":"10.1007/s44313-026-00127-4","DOIUrl":"10.1007/s44313-026-00127-4","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) infection is well-known for its high prevalence rate, association with several diseases including cancer and autoimmune conditions, and a wide variety of symptoms and prognosis. When acquired at a young age, primary infections are often asymptomatic; however, in adolescence and young adulthood, symptomatic infections develop, such as in infectious mononucleosis. A special feature of EBV infection is its ability to establish a latent infection in B cells which can lead to long-term infection. Subsequent cellular transformation and viral protein expression can result to EBV-mediated carcinogenesis. Latent proteins expressed by EBV play a role in the pathogenesis of EBV infection and carcinogenesis. These proteins are responsible for a diverse range of functions including cell transformation, cell reprogramming, immune evasion, immune suppression, angiogenesis, cell cycle regulation, and B-cell receptor mimicry.EBV infection is associated with diffuse large B-cell lymphoma, Hodgkin lymphoma, NK/T cell lymphoma, Burkitt lymphoma, post-transplant lymphoproliferative disorders, and primary CNS lymphoma. The clinical presentation varies depending on the specific disease and EBV status, with EBV-positive lymphomas generally associated with poorer prognosis than EBV-negative cases.This review aimed to examine the current understanding of the pathogenesis of EBV-associated lymphoma and to evaluate emerging and accepted therapeutic strategies.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373332","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 ResearchPub Date : 2026-03-06DOI: 10.1007/s44313-026-00126-5
Kyoung Il Min, Gi-June Min, Ki-Seong Eom, Seok-Goo Cho
{"title":"Rapidly progressive varicella zoster virus vasculopathy in a chemotherapy- and steroid-immunosuppressed patient with refractory diffuse large B-cell lymphoma: diagnostic and therapeutic challenges.","authors":"Kyoung Il Min, Gi-June Min, Ki-Seong Eom, Seok-Goo Cho","doi":"10.1007/s44313-026-00126-5","DOIUrl":"10.1007/s44313-026-00126-5","url":null,"abstract":"<p><p>Varicella zoster virus (VZV) vasculopathy is a rare but severe neurological complication that frequently results in a reversible cerebral vasoconstriction syndrome (RCVS). Diagnosis is often delayed because early manifestations are nonspecific and radiologic findings often overlap with those of other cerebrovascular disorders. We describe the fatal case of a heavily pretreated 60-year-old man with refractory diffuse large B-cell lymphoma undergoing evaluation for chimeric antigen receptor (CAR) T-cell therapy. The patient developed multifocal intracranial arterial stenosis and an acute infarction during chemotherapy-induced immunosuppression. The initial radiological features suggested RCVS; however, cerebrospinal fluid (CSF) analysis using polymerase chain reaction (PCR) and anti-IgG antibodies confirmed the presence of VZV. Despite intravenous acyclovir and high-dose corticosteroids, the vasculopathy progressed rapidly, resulting in recurrent infarctions, seizures, and death. This case highlights the diagnostic complexity of VZV vasculopathy in immunocompromised patients and underscores the importance of early CSF evaluation, heightened clinical vigilance for opportunistic viral complications, and the potential diagnostic value of vessel wall magnetic resonance imaging (MRI) in differentiating VZV vasculopathy from mimicking conditions such as RCVS.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365915","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":"Discordance between immunofixation and free light chain assays in multiple myeloma: a retrospective analysis and evaluation of the heavy/light chain assay for disease monitoring.","authors":"Oytip Nathalang, Yupapin Onthong, Chonlada Laoruangroj, Dollapak Apipongrat","doi":"10.1007/s44313-026-00130-9","DOIUrl":"10.1007/s44313-026-00130-9","url":null,"abstract":"<p><strong>Background: </strong>Accurate detection and monitoring of monoclonal proteins in multiple myeloma (MM) are critical for diagnosis and treatment guidance. Conventional assays such as serum protein electrophoresis (SPEP), immunofixation electrophoresis (SIFE), and serum-free light chain (SFLC) testing can yield discordant or inconclusive results, particularly in patients with low M-protein levels.</p><p><strong>Objectives: </strong>To evaluate the concordance and discordance between SIFE and SFLC assays in MM and to assess the clinical utility of the heavy/light chain (HLC) assay as a complementary quantitative tool.</p><p><strong>Methods: </strong>We retrospectively analyzed 1,310 MM patient samples. The concordance and discordance between SIFE and SFLC were assessed, and the analytical performance of HLC measurements was evaluated relative to conventional assays.</p><p><strong>Results: </strong>The overall discordance rate between SIFE and SFLC was 26.9%, with SIFE-/SFLC + most frequent in light chain MM and SIFE + /SFLC- observed in patients who achieved a very good partial response (VGPR). HLC strongly correlated with total immunoglobulins (combined immunoglobulin G [IgG]/immunoglobulin A [IgA], R<sup>2</sup> = 0.99) and SPEP (R<sup>2</sup> = 0.94). HLC ratios demonstrated excellent concordance with SIFE (κ = 0.83, 95% confidence interval [CI] 0.72-0.93) but poor agreement with SFLC ratios (κ = 0.01, 95% CI - 0.18-0.20). Using the HLC response model, 15 patients classified as having VGPR by the International Myeloma Working Group (IMWG) criteria were reclassified as having a partial response due to a dHLC reduction of < 90%.</p><p><strong>Conclusions: </strong>This large retrospective study provides a comprehensive evaluation of SIFE and SFLC discordance in MM, offering real-world evidence of their complementary diagnostic and monitoring roles. These findings support the integration of HLC testing into existing response assessment strategies to enhance the accuracy of treatment evaluation and the interpretation of discordant results.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365967","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}