Annals of Hematology最新文献

{"title":"Chidamide plus venetoclax as effective and safe maintenance therapy in high-risk acute myeloid leukemia and myelodysplastic syndrome post-transplantation","authors":"Cuicui Lyu,&nbsp;Haotian Meng,&nbsp;Yedi Pu,&nbsp;Xianshuang Luan,&nbsp;Hairong Lyu,&nbsp;Xia Xiao,&nbsp;Mingfeng Zhao","doi":"10.1007/s00277-026-07221-8","DOIUrl":"10.1007/s00277-026-07221-8","url":null,"abstract":"<div><p>Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the leading cause of treatment failure in high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), yet effective maintenance strategies are currently lacking. The combination of chidamide (CHI) and venetoclax (VEN) represents a novel approach. However, real-world data on its use are limited. In this study, eighteen high-risk transplant recipients received maintenance therapy with CHI (5 mg/day on days 1–7 or 1–14) plus VEN (100 mg on day 1, then 200 mg on days 2–7 or 2–14) every 2 months. Endpoints included overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and safety. After a median follow-up of 708 days, the 2-year OS and DFS were 73.9% and 56.6%, respectively. The 2-year CIR was 28.9%, and the 2-year NRM rate was 22.5%. The most common adverse events were hematologic, including neutropenia (13 episodes), thrombocytopenia (7), and anemia (7), all of which were manageable. No treatment-related mortality, tumor lysis syndrome, or severe acute graft-versus-host disease (GVHD) occurred. In conclusion, CHI plus VEN as post-transplant maintenance therapy shows encouraging efficacy and a manageable safety profile in high-risk AML/MDS patients, representing a promising strategy for relapse prevention.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07221-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term follow-up of ruxolitinib pre-approval use in acute and chronic graft-versus-host disease","authors":"Raphael Loisl,&nbsp;Anna Bauhofer,&nbsp;Alexander Nikoloudis,&nbsp;Robert Milanov,&nbsp;Sigrid Machherndl-Spandl,&nbsp;Veronika Buxhofer-Ausch,&nbsp;Michaela Binder,&nbsp;Petra Hasengruber,&nbsp;Emine Kaynak,&nbsp;Dagmar Wipplinger,&nbsp;Irene Strassl,&nbsp;Olga Saini,&nbsp;Christoph Aichinger,&nbsp;Andreas Petzer,&nbsp;Hildegard Greinix,&nbsp;Daniel Wolff,&nbsp;Johannes Clausen","doi":"10.1007/s00277-026-07217-4","DOIUrl":"10.1007/s00277-026-07217-4","url":null,"abstract":"<div><p>Steroid-refractory (SR) acute and chronic graft-versus-host disease (aGVHD/cGVHD) are frequent and serious complications after allogeneic hematopoietic stem cell transplantation. Ruxolitinib (RUX) is approved for the treatment of both conditions. Real world evidence may provide valuable complementary information beyond prospective trials because of significant divergences in study populations, endpoints, treatment strategies, and observation time. We report long-term outcomes of 118 patients with acute (n = 61), classic chronic (n = 43) and overlap chronic GVHD (n = 14) who received RUX within a named-patient-program in the pre-approval era as second-line treatment or beyond. In 22 patients, GVHD occurred after donor lymphocyte infusion (DLI). The cohort included heavily pretreated patients, with 26.2% of aGVHD in 3rd -line or beyond, and 29.8% of cGVHD in 4th -line or beyond. Only 22 patients (18.6%) met all in-/exclusion criteria of the respective pivotal phase III studies. The most frequent incompatibilities were unmet SR criteria, excessive pretreatment, previous DLI, overlap chronic GVHD, and medical/hematological criteria. Overall response rate to RUX was 68.9% in aGVHD, and 66.7% in cGVHD. In all three GVHD types, &gt; 50% of patients were able to discontinue systemic steroids. With a survivors’ median follow up of 60.3 months (range, 25.5–99.3) from RUX initiation, 4-year survival probability was 57.4% in aGVHD, 81.1% in classic cGVHD, and 78.6% in overlap cGVHD. Our findings reveal favorable survival probabilities associated with a long-term steroid-sparing/replacing potential of RUX in treatment-refractory aGVHD and cGVHD, including overlap syndrome and DLI-associated GVHD.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing venetoclax duration with hypomethylating agents for newly diagnosed acute myeloid leukemia: impact on response and survival","authors":"Anush A. Ginosyan,&nbsp;Karam Ashouri,&nbsp;Justin Cheng,&nbsp;Lauren Ford,&nbsp;Mihir Baya,&nbsp;Lucas Humayun,&nbsp;Danielle Hong,&nbsp;Elaine Huang,&nbsp;Grace Kim,&nbsp;Brandon Tang,&nbsp;Brian Hom,&nbsp;Robert Ireland,&nbsp;Imran Siddiqi,&nbsp;Amir Ali,&nbsp;Karrune Woan,&nbsp;Eric Leon Tam,&nbsp;George Yaghmour","doi":"10.1007/s00277-026-07219-2","DOIUrl":"10.1007/s00277-026-07219-2","url":null,"abstract":"<div><p>The addition of venetoclax to hypomethylating agents (HMAs) is standard for older adults with newly diagnosed acute myeloid leukemia (AML). However, prolonged venetoclax (VEN) exposure can cause cytopenias and infections, raising questions about optimal duration. We conducted a single‑center retrospective study of 102 patients treated between 2018 and 2025 with azacitidine or decitabine plus VEN administered for 14 (<i>n</i> = 22), 21 (<i>n</i> = 48), or 28 (<i>n</i> = 32) days per 28‑day cycle. Baseline cytogenetic and molecular profiling, responses by 2022/2024 ELN criteria, measurable residual disease (MRD), cumulative incidence of relapse (CIR), disease‑free survival (DFS), and overall survival (OS) were analyzed using competing‑risks regression and Cox models. Median age was 68 years and patients received a median of 4 cycles. Composite remission (CR/CRi/CRh/MLFS) was 66.7%, with MRD negativity in 75.0% of responders. Remission and MRD negativity rates did not differ significantly across VEN‑duration cohorts. Median OS and DFS were 17.3 and 12.3 months, respectively, with no significant differences in OS, DFS, and CIR between 14‑, 21‑, and 28‑day cohorts. Grade ≥ 3 cytopenias and transfusion independence rates also did not differ significantly. In this cohort, shortening VEN exposure to 14 or 21 days did not show a significant difference in response, survival, relapse risk, and toxicity profiles relative to a 28‑day schedule in our cohort. These findings support further prospective evaluation of reduced VEN durations in this population.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mortality model for relapsed or refractory multiple myeloma: emulation of subjective life expectancy criteria from a clinical trial in real-world data","authors":"Alexander Breskin,&nbsp;Mostafa Shokoohi,&nbsp;Beatrice Suero,&nbsp;Di Wang,&nbsp;Paul Spin,&nbsp;Qiufei Ma,&nbsp;Glenn S. Kroog,&nbsp;Christian Hampp","doi":"10.1007/s00277-026-07200-z","DOIUrl":"10.1007/s00277-026-07200-z","url":null,"abstract":"<div><p>Patients with limited life expectancy (LE) are often excluded from oncology trials based on subjective judgment, posing a challenge when contextualizing trial findings with real-world data (RWD). This study evaluated the feasibility of modeling mortality in RWD for relapsed/refractory multiple myeloma (RRMM) to replicate patient exclusion (LE &lt; 6 months) for application in an external control arm study.</p><p>A targeted literature review (TLR, January 2016–March 2022) was performed to identify mortality prediction models in RRMM. Because no suitable model was found, a de novo mortality model was developed using the COTA database.</p><p>Twenty-one prognostic factors identified via literature review and clinical experts were included in the models. Cox proportional hazards models with bootstrap validation to correct for optimism were used to identify the best-performing model. A threshold of ≥50% predicted mortality probability within 6 months of the start of the line of therapy (LOT) was used for sensitivity and specificity estimates.</p><p>Patients (<i>N</i> = 1,112) contributed 2,626 LOTs. A model with the top 20 prognostic factors maximized concordance and accuracy while achieving pre-specified performance thresholds, except for the F1 score. The predicted and observed 6-month mortality probability were both 26%.</p><p>Mortality prediction for RRMM remains challenging with RWD. The de novo model exhibited strong discrimination performance but low F1 score, suggesting it may be useful to identify patients at highest risk who may be least likely to meet trial LE criteria.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"30 years in service, 1996–2026: Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)","authors":"Oliver A. Cornely,&nbsp;Georg Maschmeyer,&nbsp;Wolfgang Hiddemann,&nbsp;Nico Bekaan,&nbsp;Nicola Giesen,&nbsp;Cornelia Lass-Flörl,&nbsp;Sibylle C. Mellinghoff,&nbsp;Verena Petzer,&nbsp;Jon Salmanton-García,&nbsp;Michael Sandherr,&nbsp;Enrico Schalk,&nbsp;Xaver Schiel,&nbsp;Martin Schmidt-Hieber,&nbsp;Danila Seidel,&nbsp;Jannik Stemler,&nbsp;Daniel Teschner,&nbsp;Laura N. Walti,&nbsp;Christina T. Rieger","doi":"10.1007/s00277-026-07194-8","DOIUrl":"10.1007/s00277-026-07194-8","url":null,"abstract":"<div><p>The Infectious Diseases Working Party (AGIHO) was established in 1996 as one of the subgroups of the German Society of Hematology and Medical Oncology (DGHO). Marking its 30th anniversary this year, the AGIHO reflects on a period of significant achievement and growth. Beyond its core mission of developing evidence-based clinical practice guidelines for the prevention, diagnosis, and management of infections in patients with cancer, the AGIHO has evolved into a vital platform for clinical trials, collaborative research, and postgraduate medical education. To ensure long-term sustainability and foster emerging talent, “Young AGIHO” was launched in 2023. This initiative aims to strengthen networking among early career physicians specializing in hematology and oncology with a strong focus on infectious diseases. The working party has also expanded its geographical footprint by integrating colleagues from Austria and Switzerland, thereby enhancing its international presence. Through the publication of guidelines in high-ranking international journals, AGIHO visibility has increased significantly. Representatives of the working party now serve as experts for scientific and health policy committees both nationally and internationally. As one of the DGHO's largest and most active subgroups, the AGIHO is ideally positioned to address future challenges in the field.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous regression of B-cell acute lymphoblastic leukemia with PAX5 alterations at relapse: a case report","authors":"Vadim Lesan,&nbsp;Joerg Bittenbring,&nbsp;Sarah Altmeyer","doi":"10.1007/s00277-026-06825-4","DOIUrl":"10.1007/s00277-026-06825-4","url":null,"abstract":"<div><p>Acute lymphoblastic leukemia is the most common pediatric hematological disease representing less than 1% of hematological diseases in adults. The prognosis of ALL improved significantly in the last decades. Almost all patients require a therapy at the time of diagnosis. Rare cases of spontaneous remission of ALL have been described. We report a case of B-ALL that underwent spontaneous remission after an episode of infection and describe the cytogenetic changes associated with this uncommon clinical presentation of B-ALL.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-06825-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between proton pump inhibitor co-medication and treatment switching in dasatinib-treated patients with chronic myeloid leukemia: a German real-world evidence study","authors":"Sabrina Mueller,&nbsp;Chen-Chia Pan,&nbsp;Jan Bosák,&nbsp;Jiří Hofmann,&nbsp;Florian O. Losch,&nbsp;Thomas Wilke,&nbsp;Barthold Deiters,&nbsp;Daniela Žáčková","doi":"10.1007/s00277-026-07211-w","DOIUrl":"10.1007/s00277-026-07211-w","url":null,"abstract":"<div><p>Dasatinib absorption is pH-dependent, and concomitant use of Proton Pump Inhibitors (PPIs) can substantially reduce dasatinib exposure. Whether this interaction has clinical relevance and affects treatment outcomes in patients with chronic myeloid leukemia (CML) remains unclear. This retrospective cohort study used German statutory health insurance claims data (2010 − 2024). Adults with CML who initiated dasatinib treatment were selected. Patients were classified according to concomitant PPI use around dasatinib initiation. The primary endpoint was time to switch to another systemic CML therapy. Two analytical cohorts were evaluated (incident and prevalent cohorts). Propensity score matching and Cox proportional hazards models were used to compare patients with and without PPI co-medication. Sensitivity analyses censored follow-up at severe adverse events and restricted the population to users of the originator dasatinib formulation. Among 297 dasatinib patients in the incident and 372 in the prevalent cohort, PPI co-medication was observed in approximately 19–21% of patients. After matching, concomitant PPI use was consistently associated with earlier treatment switching. This association reached statistical significance in the prevalent cohort (hazard ratio: 1.87, 95% CI 1.18–2.95; p = .008) and was directionally consistent in the incident cohort. Sensitivity analyses yielded directionally consistent findings. In this large real-world analysis, concomitant PPI use was associated with earlier treatment switching in dasatinib-treated patients with CML. While causality cannot be established, these findings are consistent with the known pH-dependent interaction and reinforce existing recommendations to avoid PPI co-medication during dasatinib therapy whenever feasible.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07211-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and treatment of familial hemophagocytic lymphohistiocytosis with isolated central nervous system involvement: A case report","authors":"Hongli Hu,&nbsp;Yubo Pi,&nbsp;Jingshi Wang,&nbsp;Zhao Wang","doi":"10.1007/s00277-026-07208-5","DOIUrl":"10.1007/s00277-026-07208-5","url":null,"abstract":"<div><p>Familial hemophagocytic lymphohistiocytosis (FHL) is the prototypical genetic form of hemophagocytic lymphohistiocytosis (HLH), a potentially fatal hyperinflammatory condition. Limited awareness of HLH with isolated central nervous system (CNS) involvement often leads to underdiagnosis or diagnostic delay. Here, we report a 13-year-old girl with FHL type 3 (FHL3) presenting with isolated CNS involvement who subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT). This case expands the clinical spectrum of FHL3 and highlights that isolated neurological symptoms may be the initial or sole manifestation of FHL, even without systemic signs. Allogeneic HSCT remains the only definitive therapy for FHL. The patient received a conditioning regimen comprising thiotepa, etoposide, busulfan, cyclophosphamide, and antithymocyte globulin (TT/VP16/BU/CY/ATG). The graft consisted of 20.4 × 10⁸/kg mononuclear cells and 4.71 × 10⁶/kg CD34 + cells. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A (CsA), mycophenolate mofetil (MMF), and methotrexate (MTX). Neutrophil engraftment (absolute neutrophil count ≥ 0.5 × 10⁹/L) occurred on day + 13, and platelet engraftment (≥ 20 × 10⁹/L) on day + 19. The patient did not develop GVHD and achieved full, stable donor chimerism with successful engraftment and minimal toxicity. Neurological remission was observed following transplantation. At the last follow-up on day 679, the patient remained alive without neurological relapse or systemic HLH. In conclusion, this patient achieved long-term CNS remission and correction of the underlying molecular defect following allogeneic HSCT with a TT/VP16/BU/CY/ATG conditioning regimen.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07208-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reinterpreting the matched-sibling relapse penalty in ATG-based allogeneic transplantation for myelodysplastic neoplasms: a question of dose, not donor","authors":"Naif I. AlJohani","doi":"10.1007/s00277-026-07209-4","DOIUrl":"10.1007/s00277-026-07209-4","url":null,"abstract":"<div><p>Park and colleagues recently reported, in a single-centre Korean cohort of 391 adult patients with myelodysplastic neoplasms (MDS) receiving fludarabine–busulfan conditioning and antithymocyte globulin (ATG)-based prophylaxis, that matched sibling donor (MSD) recipients experienced a substantially higher 5-year cumulative incidence of relapse (34.3%) than recipients of unrelated (UD; 16.4%) or haploidentical (HID; 16.8%) donors, with reduced acute and chronic graft-versus-host disease (GVHD) in the MSD arm. The authors conclude that under ATG-based prophylaxis, MSD may no longer be the optimal donor choice in MDS. We respectfully argue that this conclusion is constrained by two structural features of the cohort. First, ATG dose is severely confounded with donor type: 61.3% of MSD recipients received 10 mg/kg ATG versus 0% of HID recipients, a dose pattern that inverts standard clinical practice and overlaps a range in which independent evidence indicates impaired disease control without offsetting GVHD benefit. Second, the GVHD- non-relapse mortality pattern in the cohort is more consistent with a cumulative immunosuppression-intensity hypothesis than with a primary donor-source effect. We propose that the most clinically actionable inference is to re-examine ATG dosing in MSD transplants for MDS, rather than to displace MSD as a preferred donor.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07209-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary central nervous system lymphoma in the molecular era: genomic drivers, liquid biopsy, and targeted therapeutic strategies","authors":"Feng Yan,&nbsp;Yongzhi Shan,&nbsp;Xiaotong Fan,&nbsp;Yaming Wang,&nbsp;Penghu Wei,&nbsp;Yongrui Zhao,&nbsp;Yixian Guo","doi":"10.1007/s00277-026-07216-5","DOIUrl":"10.1007/s00277-026-07216-5","url":null,"abstract":"<div><p>Primary central nervous system lymphoma (PCNSL) is an uncommon and aggressive extranodal non-Hodgkin lymphoma confined to the central nervous system, including the brain, leptomeninges, spinal cord, and eyes. Although high-dose methotrexate-based induction remains the backbone of first-line therapy, long-term disease control remains challenging, particularly in older or frail patients and in those with relapsed or refractory disease. Recent genomic and multi-omics studies have reshaped the biological understanding of PCNSL by identifying recurrent alterations in <i>MYD88</i>, <i>CD79B</i>, <i>PIM1</i>, <i>PRDM1</i>, <i>CDKN2A/B</i>, HLA-related genes, <i>B2M</i>, <i>CIITA</i>, and immune checkpoint loci, which converge on B-cell receptor/Toll-like receptor signaling, NF-κB activation, immune evasion, and microenvironmental adaptation. These molecular insights have accelerated minimally invasive diagnostics, including targeted mutation assays, multigene circulating tumor DNA profiling, methylation-based approaches, and cytokine analysis in cerebrospinal fluid, vitreous humor, and aqueous humor. Targeted and immune-based therapies, including Bruton tyrosine kinase inhibitors, immunomodulatory agents, immune checkpoint inhibitors, mTOR inhibitors, and CD19-directed chimeric antigen receptor T-cell therapy, have shown variable degrees of clinical activity, particularly in relapsed or refractory disease. However, most evidence remains derived from early-phase trials, single-arm studies, retrospective cohorts, or small series, and treatment selection is not yet routinely biomarker-defined. This review summarizes current advances in molecular taxonomy, pathogenesis, diagnostic work-up, liquid biopsy, prognostic stratification, and therapeutic management of PCNSL, emphasizing how molecular and longitudinal biomarker data may inform individualized treatment and future clinical trial design.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}