Annals of Hematology最新文献

{"title":"Acute myeloid leukemia and gut microbiome: bidirectional effects and opportunities for intervention","authors":"Kirti Arora,&nbsp;Rishi Chowdhary,&nbsp;Aditi Shenoy,&nbsp;Chitresh Kapadia,&nbsp;FNU Paras,&nbsp;Nancy Vora,&nbsp;Aditi Arora,&nbsp;Rahul Chowdhary,&nbsp;Aryan Arora,&nbsp;Manjeet Goyal,&nbsp;Laurie Matt-Amaral","doi":"10.1007/s00277-026-07176-w","DOIUrl":"10.1007/s00277-026-07176-w","url":null,"abstract":"<div><p>Acute myeloid leukaemia (AML) is characterized by substantial treatment-related morbidity that is not fully explained by cytogenetic or molecular risk stratification alone. Emerging evidence implicates the gut microbiome as a critical, modifiable determinant of AML pathogenesis, therapeutic response, and treatment-related complications. Patients with AML exhibit profound gut microbiome disruption at diagnosis, marked by reduced microbial diversity and depletion of short-chain fatty acid–producing commensals, which is further exacerbated by intensive chemotherapy, antibiotic exposure, and hematopoietic stem cell transplantation (HSCT). These perturbations impair intestinal barrier integrity, amplify systemic inflammation, and promote domination by opportunistic and multidrug-resistant organisms, thereby increasing the risks of mucositis, bloodstream infections, graft-versus-host disease, and mortality. Beyond complications, microbiome-derived metabolites modulate immune signalling, hematopoietic homeostasis, and inflammatory pathways relevant to clonal haematopoiesis and leukemogenesis, suggesting bidirectional interactions between the microbiome and AML biology. Observational and translational studies demonstrate that preserved microbial diversity and enrichment of specific taxa are associated with improved survival following HSCT, while dysbiosis correlates with inferior outcomes. Interventions aimed at microbiome preservation and restoration—including antibiotic stewardship, dietary modulation, autologous or donor fecal microbiota transplantation, and emerging postbiotic strategies—have shown feasibility and biologic efficacy, although definitive clinical benefit remains to be established. This review synthesizes current mechanistic, clinical, and translational evidence linking gut microbiome dysregulation with AML outcomes, highlights emerging therapeutic strategies, and outlines key challenges and future directions. Integrating microbiome-focused supportive care into AML management represents a promising avenue to reduce treatment toxicity and improve patient outcomes.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07176-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444087","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":"Prophylaxis and management of thromboembolism in pnh patients: an italian survey","authors":"Anna Paola Iori,&nbsp;Rosario Notaro,&nbsp;Martina Salvatori,&nbsp;Camilla Frieri,&nbsp;Eros Di Bona,&nbsp;Antonio De Vivo,&nbsp;Simona Sica,&nbsp;Andrea Patriarca,&nbsp;Francesco Lanza,&nbsp;Alessandra Ricco,&nbsp;Fabio Giglio,&nbsp;Antonella Sau,&nbsp;Eloise Beggiato,&nbsp;Simona Raso,&nbsp;Alessandro Costa,&nbsp;Amalia Figuera,&nbsp;Maria Bruna Greve,&nbsp;Filippo Achille Brioschi,&nbsp;Marica Laurino,&nbsp;Giulio Giordano,&nbsp;Elisabetta Metafuni,&nbsp;Francesca D’adamo,&nbsp;Teresa Maria Santeramo,&nbsp;Angela Amendola,&nbsp;Giorgia Mancini,&nbsp;Bruno Fattizzo","doi":"10.1007/s00277-026-07045-6","DOIUrl":"10.1007/s00277-026-07045-6","url":null,"abstract":"<div><p>Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disorder characterized by uncontrolled complement-mediated intravascular hemolysis and a disproportionately high thromboembolic risk. Although terminal complement inhibition (CIT) has substantially modified the disease course, reducing thromboembolic events (TE), the residual risk remains elevated and evidence-based anticoagulation guidelines are lacking. To characterize real- world practice, we conducted a nationwide, cross-sectional survey involving 24 Italian Centers caring for 291 patients, evaluating strategies for primary antithrombotic prophylaxis (PAP), secondary prophylaxis (SAP), and management of breakthrough hemolysis (BTH). Marked heterogeneity emerged. PAP prior to CIT was routinely employed in only one-third of Centers, whereas an equal proportion did not use it; the remainder adopted risk-based approaches integrating thrombophilia traits or clone size. SAP was universally administered after TE, with 75% of Centers maintaining indefinite anticoagulation regardless of CIT response. Anticoagulation during BTH was likewise variable, with LMWH as the preferred agent and duration largely dictated by biochemical resolution. These findings demonstrate substantial inter-center variability, underscoring the lack of harmonized national frameworks. The results highlight the need for structured expert consensus and standardized clinical algorithms to optimize thrombosis prevention and management in PNH in the era of complement inhibition.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07045-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444063","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":"Clinical utility of copeptin in histiocytosis-associated arginine vasopressin deficiency: a report of three cases","authors":"Luca Malatesta,&nbsp;Giuliana Marongiu,&nbsp;Francesco Pegoraro,&nbsp;Stefano Stagi,&nbsp;Marzia Mortilla,&nbsp;Marco Allinovi,&nbsp;Anna M. Buccoliero,&nbsp;Elena Sieni,&nbsp;Augusto Vaglio","doi":"10.1007/s00277-026-07179-7","DOIUrl":"10.1007/s00277-026-07179-7","url":null,"abstract":"<div><p>Arginine vasopressin deficiency (AVP-D) is a frequent complication of histiocytosis and may precede the systemic manifestations of the disease of several years. Currently, no reliable biomarkers allow the diagnosis of AVP-D in the setting of histiocytosis. Traditional diagnostic methods, such as the water deprivation test, are often impractical. Copeptin, a new surrogate marker for arginine vasopressin, has been used for the diagnosis of AVP-D in other conditions, such as trauma and malignancies. We herein report three clinical cases of systemic histiocytosis (one Erdheim-Chester disease, one Rosai-Dorfman-Destombes disease, and one Langerhans cell histiocytosis) where plasma copeptin was utilized to identify AVP-D. The three cases differed not only because of the underlying diagnosis, but also in terms of clinical characteristics and rapidity of onset of AVP-D. We propose an early integration of copeptin into the diagnostic workup of systemic histiocytosis.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454400","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":"Successful eradication of de novo HLA antibodies with daratumumab in immune-mediated cytopenias after allogeneic stem cell transplantation: a case report","authors":"Xianfu Sheng,&nbsp;Tonglin Hu,&nbsp;Hangping Ge,&nbsp;Huijin Hu,&nbsp;Linlin Huang,&nbsp;Baodong Ye,&nbsp;Yu Zhang","doi":"10.1007/s00277-026-07150-6","DOIUrl":"10.1007/s00277-026-07150-6","url":null,"abstract":"<div><p>Refractory immune-mediated cytopenias (IMCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are a challenging complication with limited therapeutic options. Although preexisting human leukocyte antigen (HLA) antibodies, particularly donor-specific antibodies (DSAs), are well-established risk factors for graft failure, the clinical significance and mechanistic role of de novo HLA antibodies emerging after transplantation remain poorly defined. Whether such antibodies are associated with posttransplant IMCs has not been systematically explored. We report two patients with severe aplastic anemia who developed refractory IMCs after allo-HSCT in association with high-titer de novo HLA antibodies and preserved full donor chimerism. In case 1, combined HLA class I and II antibodies were detected in association with trilineage cytopenia. Rituximab, corticosteroids and plasma exchange reduced HLA class II antibodies (including DSAs), whereas persistent HLA class I antibodies were linked to ongoing pancytopenia despite multi-agent treatment. In case 2, isolated high-titer de novo HLA class II antibodies were detected in association with late-onset thrombocytopenia, refractory to corticosteroids and rituximab. In both patients, plasma cell–directed therapy with daratumumab led to definitive clearance of de novo HLA antibodies and was followed by rapid and sustained hematologic recovery, including coordinated trilineage recovery in case 1 and selective platelet recovery in case 2. These cases provide initial hypothesis-generating observations that de novo HLA antibodies are associated with and may contribute to refractory IMCs after allo-HSCT. The concordance across antibody class, lineage-specific or multilineage hematopoietic injury, and lineage-matched recovery after antibody clearance suggests a functional immunophenotype–hematopoietic phenotype coupling that warrants further investigation.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07150-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444118","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":"Simultaneous onset of familial hemophagocytic lymphohistiocytosis and T-cell large granular lymphocytic leukemia in an adult","authors":"Friederike Dierks,&nbsp;Finn-Ole Paulsen,&nbsp;Kai Lehmberg,&nbsp;Andreas Rosenwald,&nbsp;Carsten Bokemeyer,&nbsp;Katja Weisel,&nbsp;Christoph Seidel","doi":"10.1007/s00277-026-07177-9","DOIUrl":"10.1007/s00277-026-07177-9","url":null,"abstract":"<div><p>Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome. The familial form (fHL), associated with specific genetic alterations, typically manifests in childhood, while secondary forms arise due to triggers such as malignancies or infections. We present the rare case of adult-onset fHL in a 30-year-old female concurrent with T-cell large granular lymphocytic leukemia (T-LGL). After presenting with symptoms of HLH, a bone marrow biopsy revealed T-cell lymphoma, leading to CHOEP treatment. This diagnosis was later revised to T-LGL, prompting a switch to methotrexate for T-LGL treatment. Further genetic testing uncovered an unexpected homozygous missense mutation in <i>UNC13D</i> (p.R414C), associated with fHL type 3. A detailed family history revealed a consanguineous marriage between her parents, which likely increased the risk of the homozygous mutation. Additionally, it was discovered that the patient’s sister had undergone allogeneic stem cell transplantation during childhood for an unspecified lymphoproliferative disorder, with the patient herself serving as the donor. This case highlights the rare occurrence of adult-onset fHL, triggered by the evolution of T-LGL as a possible contributing factor. It underscores the importance of early diagnosis and illustrates how familial history and persistent symptoms can necessitate genetic testing.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07177-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444052","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":"Peripheral blood CD8 + T-cell count at diagnosis predicts prognosis in R-CHOP-treated diffuse large B-cell lymphoma patients","authors":"Fang Chen,&nbsp;Ping Liu,&nbsp;Jiajia Zhao,&nbsp;Demin Wang,&nbsp;Haifeng Zhen,&nbsp;Juan Jin,&nbsp;Zhi Chao,&nbsp;Dan Zhou,&nbsp;Lu Zhang,&nbsp;Wei Chen,&nbsp;Zimian Luo,&nbsp;Zhongjun Huo","doi":"10.1007/s00277-026-07135-5","DOIUrl":"10.1007/s00277-026-07135-5","url":null,"abstract":"<div><p>While the prognostic significance of peripheral blood (PB) lymphocyte counts in diffuse large B-cell lymphoma (DLBCL) patients treated with Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine Sulfate, and Prednisone (R-CHOP) is established, the specific role of CD8+ T-cell counts (CD8c) remains unclear. Methods: This retrospective study analyzed 315 newly diagnosed DLBCL patients treated at Central Hospital of Xiangtan from January 2018 to September 2023. We evaluated the prognostic significance of initial CD8c and other clinical parameters using univariate and multivariate survival analyses to identify independent predictors of outcome. An optimal CD8c cut-off value of 264.5×10⁶/L was identified. Low CD8c correlated with significantly improved 5-year progression-free survival (PFS) (88.78% vs 49.18%, <i>p</i>&lt;0.001) and overall survival (OS) (84.02% vs 31.25%, <i>p</i>&lt;0.001). Multivariate analysis confirmed CD8c as an independent prognostic factor for both PFS and OS. CD8c demonstrated significant interactions with lactate dehydrogenase levels. Notably, low CD8c groups consistently exhibited superior survival outcomes, even in the presence of other poor prognostic factors. Initial PB CD8c serves as an independent predictor for R-CHOP-treated DLBCL patients. These findings suggest CD8c may be a candidate for enhancing existing prognostic models, particularly when combined with established risk factors, underscoring the potential importance of host immune status in DLBCL prognosis and treatment outcomes. Independent validation in external cohorts is needed.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454366","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":"UGT1A1 polymorphisms and gallbladder-related outcomes in sickle cell disease in Brazil","authors":"Fernando Ferreira Costa,&nbsp;Kleber Yotsumoto Fertrin","doi":"10.1007/s00277-026-07149-z","DOIUrl":"10.1007/s00277-026-07149-z","url":null,"abstract":"<div><p>Gallbladder complications represent a significant source of morbidity in sickle cell disease, with <i>UGT1A1</i> promoter polymorphisms associated with a higher frequency of hyperbilirubinemia and cholelithiasis in affected patients and the first publications regarding this issue appeared in the literature in early 2000. There are at least three published papers providing evidence that supports this association in the Brazilian population published in 2003, 2017 and 2021. Belisário et al., very recently published a paper in <i>Annals of Hematology</i> (“Laboratory and genetic characteristics associated with gallbladder-related outcomes in sickle cell disease in Brazil: results from the REDS-III multicenter cohort study.” <i>Annals of Hematology.</i> 2026; 105(4):115) in which they claim that it is the first study in Brazilian population concerning this issue. In our opinion the previous published papers should be cited in the References, because certainly will provide readers with a more accurate and complete picture of the field´s evaluation in Brazil.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07149-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434838","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":"MRD-driven HDACi-based therapy post-transplant: a real-world study in high-risk acute myeloid leukemia","authors":"Wei Ling,&nbsp;Ping Wu,&nbsp;Suijing Wu,&nbsp;Chengwei Luo,&nbsp;Lisi Huang,&nbsp;Xiaomei Chen,&nbsp;Xiaoling Liang,&nbsp;Zhilun Li,&nbsp;Ruohao Xu,&nbsp;Jiaqi Tan,&nbsp;Jinghua Wang,&nbsp;Peilong Lai,&nbsp;Xin Du,&nbsp;Jianyu Weng","doi":"10.1007/s00277-026-07117-7","DOIUrl":"10.1007/s00277-026-07117-7","url":null,"abstract":"<div><h3>Background</h3><p>Relapse remains a major challenge limiting long-term survival in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Measurable residual disease (MRD) is a critical independent prognostic predictor in high-risk AML. While MRD-driven prophylactic or preemptive interventions hold promise for relapse prevention, optimal therapeutic strategies remain lacking. We investigated the efficacy and safety of chidamide, a selective histone deacetylase (HDAC) inhibitor with dual epigenetic and immunomodulatory properties, within MRD-adapted post-transplant strategies in high-risk AML.</p><h3>Methods</h3><p>This pilot study analyzed 43 consecutive AML patients with high-risk AML, including pre-transplant relapsed/refractory or MRD-positive, or post-transplant MRD-positive who received Chidamide-based therapy after allo-HSCT between December 2020 and July 2023. Patients who were MRD-negative post-transplant (n=17) received prophylactic therapy, while those who were MRD-positive or relapsed post-transplant (n=26) underwent preemptive intervention. Primary endpoints included relapse-free survival (RFS) and overall survival (OS). Secondary endpoints included MRD negativity rates, toxicity (CTCAE v5.0), and changes in peripheral blood lymphocyte subsets. Statistical analyses employed Kaplan-Meier methods and Log-rank tests for survival, Chi-square/Fisher's exact tests for categorical variables, and paired t-tests for lymphocytes subsets.</p><h3>Results</h3><p>At a median follow-up of 742 days, the overall sustained remission rate was 60.4%. In the preemptive group, Chidamide-based therapy achieved an 88.5% MRD conversion rate from positive to negative (median time to conversion: 50 days), with 65% maintaining sustained negativity. The prophylactic group demonstrated a 58.8% sustained MRD-negative rate. The 6-month and 1-year RFS and OS rates for the entire cohort were 79%, 69.8% and 100%, 72.1%, respectively. No statistically significant difference in RFS or OS was observed between the preemptive and prophylactic groups (P&gt;0.05 for both). Grade 3/4 hematologic toxicities occurred in 32.6% (neutropenia) and 20.9% (thrombocytopenia) of patients, with no GVHD exacerbation observed. Chidamide treatment significantly increased peripheral blood CD8+ T cells (P=0.033) while reducing CD4+ T cells (P=0.007), suggesting enhanced cytotoxic potential.</p><h3>Conclusion</h3><p>Chidamide-based MRD-driven therapy demonstrates promising durable MRD eradication and clinically relevant survival rates in high-risk AML patients post transplant, potentially mediated by its dual epigenetic and immunomodulatory effects, including T-cell modulation. While limited by its retrospective nature and single-center design, these real-world findings support further investigation of HDAC inhibitor-based MRD-directed algorithms in prospective studies (NCT06066905).</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07117-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429686","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":"The clinical relevance of RAS pathway gene mutations in childhood B-cell acute lymphoblastic leukemia","authors":"Xiaoyu Chen,&nbsp;Li Gao,&nbsp;Yongping Zhang,&nbsp;Yixin Hu,&nbsp;Jian Pan,&nbsp;Zhiheng Li,&nbsp;Jun Lu,&nbsp;Yizhen Li,&nbsp;Shaoyan Hu","doi":"10.1007/s00277-026-07164-0","DOIUrl":"10.1007/s00277-026-07164-0","url":null,"abstract":"<div><p>Objective: Notably, FLT3 and RAS pathway gene mutations represent a significant proportion of childhood B-cell acute lymphoblastic leukemia (B-ALL) cases. Our study explores whether these patients have distinct clinical features and prognostic outcomes. Methods: We retrospectively analyzed 488 pediatric B-ALL cases from the CCCG-ALL-2015 cohort using whole transcriptome sequencing to assess the clinical features of FLT3 mutations, RAS pathway alterations, and their cooperative effects. Results: 192 patients (39.3%) carried at least one RAS pathway alterations, while 76 patients (15.6%) had FLT3 mutations. Strikingly, 6 of 11 NF1-mutated patients harbored concurrent FLT3 mutations. A significant correlation was observed between FLT3 and NF1 mutations (Phi coefficient = 0.16, χ² = 13.0, p &lt; 0.001), NRAS and KRAS mutations (Phi coefficient = 0.19, χ² = 17.12, p &lt; 0.0001), NRAS and PTPN11 (Phi coefficient = 0.138, χ² = 9.54, p = 0.0042). FLT3/NF1 co-mutated patients exhibited a higher frequency of abnormal karyotypes and had significantly poorer overall survival (OS) and event-free survival (EFS) (p &lt; 0.05), particularly when compared to those without KMT2A rearrangements (p = 0.004 and p = 0.003, respectively). Collectively, RAS pathway alterations were not significantly associated with inferior OS or EFS. Multivariable Cox regression analysis confirmed that FLT3/NF1 co‑mutations were independently associated with inferior OS (HR = 12.39, 95% CI: 1.40-109.46, p = 0.024), and multivariable logistic regression analysis showed that they were also independently associated with Day 46 MRD ≥ 0.01% (OR = 9.50, 95% CI: 1.65–54.71, p = 0.01). Conclusion: Our findings suggest that FLT3/NF1 co-mutations-rather than other RAS pathway mutations, may be associated with adverse outcomes in pediatric B‑ALL, warranting further validation. Trial registration: The study was conducted with approval from the Institutional Review Board of Children’s Hospital of Soochow University (Approval number: 2019KS006).</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07164-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429643","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":"Favorable outcome in TCF3::HLF-positive pediatric B-cell acute lymphoblastic leukemia without classic metabolic complications: A case report","authors":"Komeil Hadipour,&nbsp;Erfan Abdiaei,&nbsp;Ghasem Miri-Aliabad","doi":"10.1007/s00277-026-07166-y","DOIUrl":"10.1007/s00277-026-07166-y","url":null,"abstract":"<div><p>The t(17;19)(q22;p13) translocation, generating the TCF3::HLF fusion oncogene, occurs in &lt; 1% of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and is associated with extreme chemotherapy resistance, frequent metabolic complications including hypercalcemia and disseminated intravascular coagulation (DIC), both of which have been reported with variable frequencies across published cohorts depending on the underlying TCF3::HLF fusion subtype, together with an extremely poor long-term prognosis. A 3-year-old girl with TCF3::HLF-positive BCP-ALL presented with fever, lethargy, and pancytopenia, but notably lacked hypercalcemia and overt disseminated intravascular coagulation (DIC). Cytogenetic analysis additionally revealed a high hyperdiploid karyotype (52–58 chromosomes) and duplication of 1q. She was treated with a high-risk Children’s Oncology Group (COG) protocol (prednisone, vincristine, daunorubicin, PEG-asparaginase), achieving a day-8 blast count &lt; 1000/µL and complete remission with an exceptionally low flow-cytometric MRD of less than 0.01%. She underwent myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related donor and remains in complete remission(CR) more than 2 years post-transplantation. This case suggests that TCF3::HLF-positive ALL encompasses a clinical spectrum rather than a uniformly fatal disease. The absence of classic metabolic complications and the co-occurrence of high hyperdiploidy might delineate a subgroup with a better response to intensive chemotherapy and early HSCT. Larger studies integrating detailed molecular characterization are required to substantiate this hypothesis and guide risk-adapted therapy.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07166-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418108","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}