Annals of Hematology最新文献

{"title":"Evaluation of non-opioid therapies for pain management of sickle cell disease: a literature-based review","authors":"Kayla Riley,&nbsp;Rolake Neba,&nbsp;Adenike Atanda","doi":"10.1007/s00277-026-07165-z","DOIUrl":"10.1007/s00277-026-07165-z","url":null,"abstract":"<div><p>Pain is a debilitating complication of sickle cell disease (SCD), driven by recurrent vaso-occlusive crises and chronic pain syndromes involving central sensitization and neuropathic mechanisms. Although opioid medications remain first-line therapy for acute pain, there are limitations that highlight the need for effective adjunctive approaches. Available data support non-opioid pharmacologic therapies including acetaminophen and nonsteroidal anti-inflammatory drugs as components of multimodal analgesia, with emerging evidence for therapies targeting neuropathic and centralized pain. Non-pharmacologic interventions such as cognitive behavioral therapy have also demonstrated potential benefits as adjunctive strategies in SCD pain management. This literature review examines evidence supporting non-opioid pharmacologic and non-pharmacologic therapies for pain management in SCD and is based on structured searches of PubMed, MEDLINE, and Cochrane databases.</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/s00277-026-07165-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418135","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":"Sea-blue histiocytosis and thrombocytopenia successfully treated with an mTORC1 inhibitor: a case report","authors":"Hongmin Li,&nbsp;Jie Ma,&nbsp;Yu Hu,&nbsp;Jingyao Ma,&nbsp;Guoqing Liu,&nbsp;Yunyun Wei,&nbsp;Chao Yang,&nbsp;Runhui Wu","doi":"10.1007/s00277-026-07157-z","DOIUrl":"10.1007/s00277-026-07157-z","url":null,"abstract":"<div><p>This report describes a pediatric patient with acquired sea-blue histiocytosis (SBH) and refractory immune thrombocytopenia (ITP) who harbors a heterozygous variant in <i>TSC2</i> (p.Arg1713His). The child failed to respond to conventional first-line therapies for ITP but achieved rapid platelet normalization within 1 months of sirolimus initiation. Regression of SBH was observed at 3 months post-treatment. The identification of the TSC2 variant, along with the dramatic resolution of both SBH and thrombocytopenia upon sirolimus therapy, suggests a possible association between TSC2-related mTOR pathway dysregulation, sea-blue histiocytosis, and thrombocytopenia.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410042","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":"Severe hypereosinophilia and eosinophilic myocarditis during secondary plasma cell leukemia: evidence of a paraneoplastic manifestation of aggressive myeloma evolution","authors":"Maria Elisabetta Catini,&nbsp;Matteo Garibotto,&nbsp;Margherita Castiglione Morelli,&nbsp;Alberto Tagliafico,&nbsp;Soncini Debora,&nbsp;Fabio Guolo,&nbsp;Roberto Massimo Lemoli,&nbsp;Antonia Cagnetta,&nbsp;Michele Cea","doi":"10.1007/s00277-026-07172-0","DOIUrl":"10.1007/s00277-026-07172-0","url":null,"abstract":"<div><p>Secondary plasma cell leukemia (sPCL) represents one of the most aggressive forms of Multiple Myeloma (MM) progression and remains associated with poor outcomes despite the availability of novel immunotherapeutic approaches. Severe hypereosinophilia is exceptionally rare in plasma cell neoplasms and may occasionally occur as a paraneoplastic manifestation of aggressive disease biology. In selected cases, eosinophilic infiltration can result in life-threatening organ damage, particularly involving the cardiovascular system. We report the case of a 40-year-old woman with IgG lambda MM who achieved complete remission following daratumumab-based induction therapy, autologous stem cell transplantation, and lenalidomide maintenance. Approximately one year after transplantation, she developed rapidly progressive relapse characterized by constitutional symptoms, circulating clonal plasma cells, extensive bone marrow involvement, severe hypereosinophilia, and marked cardiac biomarker elevation. Comprehensive infectious, autoimmune, and molecular investigations excluded alternative causes of eosinophilia. Cardiac magnetic resonance imaging revealed diffuse myocardial edema, increased myocardial wall thickness, extensive subendocardial late gadolinium enhancement, regional wall motion abnormalities, and left ventricular mural thrombosis, findings highly suggestive of eosinophilic myocarditis with endomyocardial involvement consistent with Loeffler syndrome. Urgent cytoreductive therapy with cyclophosphamide and dexamethasone resulted in rapid normalization of eosinophil counts, substantial clinical improvement, and reduction of cardiac symptoms, strongly supporting a pathogenetic relationship between eosinophilia and plasma cell disease burden. Despite subsequent salvage therapies, including isatuximab-based treatment and the BCMA-directed bispecific antibody elranatamab, disease control remained transient and the patient ultimately died from refractory sPCL. This case highlights severe hypereosinophilia as a rare paraneoplastic manifestation of aggressive clonal evolution in MM and emphasizes the importance of prompt recognition of eosinophilic cardiac involvement. The close correlation between eosinophil kinetics and disease activity further suggests that hypereosinophilia may represent a potential clinical indicator of aggressive plasma cell disease evolution and warrants further investigation.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07172-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418128","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":"Baseline immunonutritional status drives CAR T-cell efficacy, survival, and safety in R/R lymphoma: validation of a pre-lymphodepletion PNI threshold","authors":"Na Zhang,&nbsp;Fan Yang,&nbsp;Rui Liu,&nbsp;Zhonghua Fu,&nbsp;Danyang Li,&nbsp;Yuelu Guo,&nbsp;Lixia Ma,&nbsp;Miaomiao Cao,&nbsp;Biping Deng,&nbsp;Shilin Gan,&nbsp;Chen Chen,&nbsp;Xiaoyan Ke,&nbsp;Kai Hu","doi":"10.1007/s00277-026-07171-1","DOIUrl":"10.1007/s00277-026-07171-1","url":null,"abstract":"<div><p>Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape for relapsed/refractory (R/R) lymphoma. However, heterogeneous responses and treatment-related toxicities remain significant challenges. The prognostic nutritional index (PNI), reflecting both nutritional status and systemic immune competence, has emerged as a potential biomarker in various malignancies. This study aimed to evaluate the predictive value of the PNI assessed specifically prior to lymphodepletion in patients with R/R lymphoma receiving CAR T-cell therapy. We retrospectively analyzed 449 patients with R/R lymphoma treated with CAR T cells. The PNI was calculated using serum albumin levels and absolute lymphocyte counts measured before administering lymphodepleting chemotherapy. The optimal PNI cutoff for predicting survival was determined to be 39.2 using maximally selected rank statistics. The patients were stratified into high-PNI (&gt; 39.2, <i>n</i> = 363) and low-PNI (≤ 39.2, <i>n</i> = 86) groups on the basis of the PNI cutoff value. The median age of the patients was 52 years. All patients had R/R aggressive B-cell lymphoma and were treated with CAR T cells. Compared with patients in the low-PNI group, patients in the high-PNI group achieved significantly superior clinical responses, with higher overall response rates (ORRs: 65.5% vs. 44.2%, <i>P</i> &lt; 0.001) and complete response rates (CRRs: 52.2% vs. 27.9%, <i>P</i> &lt; 0.001). The median follow-up period was 33.12 months, and long-term survival markedly improved among patients in the high-PNI group; the 5-year overall survival (OS) rates were 59.02% vs. 21.88% (<i>P</i> &lt; 0.001), and the 5-year progression-free survival (PFS) rates were 42.69% vs. 13.29% (<i>P</i> &lt; 0.001) for patients in the high- and low-PNI groups, respectively. In terms of safety, multivariate analysis confirmed that a high PNI independently reduced the risk of any-grade CRS (<i>P</i> = 0.047), but was not significantly associated with grade ≥ 3 CRS (<i>P</i> = 0.121). No significant association was observed between a high PNI and the occurrence or severity of ICANS (all <i>P</i> &gt; 0.05). Multivariate analysis revealed that a PNI &gt; 39.2 remained an independent predictor of both OS (HR = 0.425, <i>P</i> &lt; 0.001) and PFS (HR = 0.542, <i>P</i> &lt; 0.001). The pre-lymphodepletion PNI is a simple, noninvasive, and robust tool for predicting therapeutic efficacy, long-term survival, and treatment-related toxicity in patients with R/R lymphoma receiving CAR T-cell therapy. A PNI threshold of 39.2 provides a valuable reference for risk stratification and clinical management.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409995","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":"Single low-dose daratumumab enhances rituximab efficacy for sustained remission in treatment-refractory autoimmune cytopenias","authors":"Xiao Long,&nbsp;Xinyi Qin,&nbsp;Hui Ke,&nbsp;Li Tang,&nbsp;Yanfang Zhang,&nbsp;Hanqing Zeng,&nbsp;Jianchuan Deng,&nbsp;Yun Luo,&nbsp;Chun Cao","doi":"10.1007/s00277-026-07159-x","DOIUrl":"10.1007/s00277-026-07159-x","url":null,"abstract":"<div><p>Treatment-refractory autoimmune cytopenias (AIC) including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and Evans syndrome (ES) lack therapies providing durable remission. We conducted a retrospective cohort study of 22 adults with refractory primary AIC who received single low-dose daratumumab (100 mg, day 0) combined with rituximab (100 mg weekly ×4 doses) and glucocorticoids. Primary endpoints were overall response rate (ORR), complete response rate (CRR), relapse-free survival (RFS), and safety. Among participants (median age 63.0 years; 81.8% female), 95.5% achieved initial response (CRR 27.3%; partial response rate 68.2%) with median time-to-response 7 days. At median follow-up 322 days, sustained ORR was 81.8% with CRR 59.1%. with disease-specific rates: CRR/ORR of 60.0%/80.0% (AIHA), 60.0%/70.0% (ITP), and 57.1%/100.0% (ES). Cumulative CRR by subtype were 75% (AIHA), 80% (ITP), and 65.7% (ES) (<i>P</i> = 0.031). The median RFS was not reached during the follow-up period. Averse events occurred in 36.4% of patients, primarily infections (27.8%; herpesvirus, urinary/respiratory tract) and rash (9.1%); all resolved with intervention. In conclusion, this dual-pathway targeting regimen induced rapid, durable hematologic responses in refractory AIC with manageable toxicity. The single low-dose daratumumab approach demonstrates significant clinical feasibility, potentially redefining therapeutic paradigms for antibody-mediated autoimmune disorders.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403340","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":"Development and validation of a radiomics nomogram for predicting outcomes following combined radiotherapy and modern chemotherapy in early-stage extranodal nasal-type NK/T-cell lymphoma: a multicenter study","authors":"Jie Gong,&nbsp;Yongchun Zhou,&nbsp;Shan Gao,&nbsp;Qiufang Liu,&nbsp;JingYi Liu,&nbsp;Yanchun Wei,&nbsp;Yanqun Zhang,&nbsp;Changhao Liu,&nbsp;Bingxin Hou,&nbsp;Lei Zhang,&nbsp;Xiaolong Li,&nbsp;Hongjuan Dong,&nbsp;Juan Feng,&nbsp;Jingjing Ren,&nbsp;Ning Su,&nbsp;Mai Zhang,&nbsp;Lina Zhao,&nbsp;Mei Shi,&nbsp;Jian Zang","doi":"10.1007/s00277-026-07170-2","DOIUrl":"10.1007/s00277-026-07170-2","url":null,"abstract":"<div><p>Compared with existing clinical prognostic indicators, the prognostic efficacy of radiomics in predicting outcomes for early-stage extranodal nasal-type NK/T-cell lymphoma(ENKTCL) patients who received combined radiotherapy and non-anthracycline-based chemotherapy is still unclear. This study aims to construct and validate a hybrid radiomics nomogram based on multicenter data. A total of 196 patients from Xijing Hospital were enrolled and were randomly divided into the training set (<i>n</i> = 147) and internal validation set (<i>n</i> = 49) at a ratio of 3:1, and 57 patients from the other three hospitals were used as the independent external validation set. Important radiomic features selected from 1316 features extracted from contrast-enhanced CT-based tumors were used to calculate radscore as the radiomic signature. The optimal clinical index was selected from four common models: International Prognostic Index(IPI), Korean Prognostic Index(KPI), prognostic index for NK/T-cell lymphomas(PINK), and nomogram-revised risk index(NRI), which was combined with radscore to construct a hybrid nomogram for predicting overall survival(OS). Twelve radiomic features that were most useful to predict OS were ultimately selected to calculate radscore. Compared with PINK, IPI, and KPI, NRI demonstrated superior prognostic performance. Furthermore, the radscore model outperformed NRI. A hybrid nomogram, named RadNRI, was constructed by integrating NRI and radscore. The RadNRI model demonstrated the highest performance with C-index of 0.815, 0.823 and 0.765 in the training, internal and external validation sets, respectively. A hybrid radiomics nomogram was constructed and validated in multicenter data, which demonstrates significant potential in forecasting prognosis of early-stage ENKTCL patients.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403315","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":"Prognostic impact of KMT2A-PTD in acute myeloid leukemia in the NGS era: a multicenter retrospective study","authors":"Taichiro Tokura,&nbsp;Satoshi Wakita,&nbsp;Keiko Fukunaga,&nbsp;Yasunobu Nagata,&nbsp;Shunsuke Yui,&nbsp;Atsushi Marumo,&nbsp;Tomoaki Kitano,&nbsp;Mayumi Yogosawa,&nbsp;Daisuke Minakata,&nbsp;Shinichi Kako,&nbsp;Shinya Kimura,&nbsp;Sho Okamoto,&nbsp;Taku Tsukamoto,&nbsp;Junya Kanda,&nbsp;Atsushi Satake,&nbsp;Haruko Tashiro,&nbsp;Masao Ogata,&nbsp;Kuniko Takano,&nbsp;Jun Ando,&nbsp;Taro Edahiro,&nbsp;Tatsuo Ichinohe,&nbsp;Yuri Kamitsuji,&nbsp;Nobuhiko Uoshima,&nbsp;Eri Kawata,&nbsp;Hitoji Uchiyama,&nbsp;Keiichi Moriya,&nbsp;Noriko Doki,&nbsp;Yuho Najima,&nbsp;Kazutaka Nakayama,&nbsp;Toshimitsu Ueki,&nbsp;Katsuhiro Shono,&nbsp;Shinichiro Mori,&nbsp;Masao Hagihara,&nbsp;Akiko Hashimoto,&nbsp;Hideharu Muto,&nbsp;Daichi Nishiyama,&nbsp;Sayuri Motomura,&nbsp;Yoshinobu Kanda,&nbsp;Hiroki Yamaguchi","doi":"10.1007/s00277-026-07158-y","DOIUrl":"10.1007/s00277-026-07158-y","url":null,"abstract":"<div><p>The <i>KMT2A</i> gene is frequently altered in acute myeloid leukemia (AML). <i>KMT2A</i> abnormalities include partial tandem duplication (PTD), single-nucleotide variants (SNVs), and chromosomal rearrangements such as t(9;11)(p21.3;q23.3) and t(v;11q23.3). However, with the widespread adoption of next-generation sequencing (NGS), PTD has been assessed less frequently. We evaluated the clinical features and prognostic impact of PTD and other <i>KMT2A</i> abnormalities. We analyzed the <i>KMT2A</i> abnormalities and coexisting genetic alterations in 585 patients with de novo AML diagnosed across 25 institutions (1991–2020). Using bone marrow and/or peripheral blood samples, we identified PTD by targeted polymerase chain reaction-based assay, chromosomal rearrangements by karyotyping, and SNVs and other genetic alterations by targeted NGS. <i>KMT2A</i> abnormalities were detected in 18.3% of de novo AML, comprising PTD in 6.7%, SNVs in 5.1%, t(9;11)(p21.3;q23.3) in 2.2%, and t(v;11q23.3) in 4.8%; 0.5% had concurrent <i>KMT2A</i> abnormalities. Patients with PTD, t(9;11)(p21.3;q23.3), or t(v;11q23.3) had significantly shorter relapse-free survival (RFS) than the <i>KMT2A</i> wild-type group (hazard ratio [HR] 1.99, <i>p</i> = 0.048; HR 3.13, <i>p</i> = 0.009; HR 2.41, <i>p</i> = 0.006, respectively). Patients with PTD, t(9;11)(p21.3;q23.3), or t(v;11q23.3) had significantly shorter overall survival (OS) than the <i>KMT2A</i> wild-type group (HR 3.92, <i>p</i> &lt; 0.001; HR 4.58, <i>p</i> &lt; 0.001; HR 3.73, <i>p</i> &lt; 0.001, respectively). Within the PTD group, older age (<i>p</i> = 0.030) and higher lactate dehydrogenase (<i>p</i> = 0.005) remained independent adverse prognostic factors. <i>KMT2A</i>-PTD is associated with inferior RFS and OS in de novo AML. Our findings support routine PTD testing at diagnosis and the incorporation of <i>KMT2A</i>-PTD into prognostic risk stratification and clinical decision-making.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395786","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":"Clonal evolution of mycosis fungoides into peripheral T-cell lymphoma: evidence from next-generation sequencing in two cases","authors":"Olga Novosad,&nbsp;Alberto Schena,&nbsp;Maria Cristina Pirosa,&nbsp;Helmut Beltraminelli,&nbsp;Luca Mazzucchelli,&nbsp;Emanuele Zucca","doi":"10.1007/s00277-026-07155-1","DOIUrl":"10.1007/s00277-026-07155-1","url":null,"abstract":"<div><p>Cutaneous T-cell lymphomas (CTCL) are characterized by marked clinical and molecular heterogeneity. Mycosis fungoides (MF), the most common subtype, usually follows an indolent course but may rarely progress into more aggressive lymphoid neoplasms. Distinguishing between clonal evolution and the development of a second, unrelated lymphoma remains a diagnostic challenge, particularly when conventional T-cell receptor (TCR) gene rearrangement analysis is inconclusive. We report two patients with long-standing, clinically stable MF who subsequently developed rapidly progressive systemic disease with histologically confirmed peripheral T-cell lymphoma (PTCL). In both cases, TCR-gamma PCR analysis suggested distinct clonal populations across different biopsy sites. However, next-generation sequencing (NGS) using a comprehensive lymphoma-targeted gene panel revealed overlapping mutational profiles between skin and lymph node samples, supporting a shared clonal origin. These findings highlight the limitations of PCR-based clonality assessment and demonstrate the added value of NGS in defining clonal relationships and disease evolution in CTCL. Improved molecular characterization may have important implications for diagnosis, classification, and therapeutic decision-making in patients with T-cell lymphomas.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395744","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":"Delayed-onset parkinsonism possibly associated with elranatamab treatment for relapsed/refractory multiple myeloma: a case report of a poorly characterized neurological event","authors":"Asuka Kono,&nbsp;Yoshihiro Umezawa,&nbsp;Kensuke Oshima,&nbsp;Keisuke Tanaka,&nbsp;Yuki Kobayashi,&nbsp;Takehiko Mori,&nbsp;Masahide Yamamoto","doi":"10.1007/s00277-026-07163-1","DOIUrl":"10.1007/s00277-026-07163-1","url":null,"abstract":"<div><p>T cell–redirecting therapies directed against B-cell maturation antigen (BCMA) have revolutionized the treatment of relapsed or refractory multiple myeloma (MM). BCMA-directed CAR-T cell therapy has been reported to cause a parkinsonism-predominant neurotoxicity referred to as movement and neurocognitive toxicity (MNT). MNT is considered distinct from immune effector cell-associated neurotoxicity syndrome (ICANS) in terms of its clinical features and time to onset. However, MNT-like delayed-onset parkinsonism has not been well documented after BCMA-directed bispecific antibody (BsAb) therapy. We report the case of a woman with relapsed/refractory MM who developed parkinsonism following elranatamab. She experienced neither cytokine release syndrome nor ICANS. Beginning the day after the Week 7 dose, she developed bradykinesia, repeated falls, gait disturbance, and cognitive decline. Neurological examination revealed hypomimia, bradykinesia, upper extremity rigidity, postural instability, and a shuffling gait, consistent with parkinsonism. Brain MRI and dopamine transporter single-photon emission computed tomography findings showed no findings suggestive of degenerative Parkinson’s disease. Her symptoms gradually improved after discontinuation of elranatamab. This case highlights the possibility of delayed-onset parkinsonism with neurocognitive symptoms following treatment with a BCMA-directed BsAb. Clinicians should recognize the potential for delayed-onset parkinsonism and ensure close neurological monitoring in patients receiving these agents.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395782","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":"Pedigree analysis of cerebral venous sinus thrombosis associated with compound heterozygous hereditary protein S deficiency","authors":"Xuanyu Chen,&nbsp;Beilei Hu,&nbsp;Buyu Ke,&nbsp;Chenyu Dai,&nbsp;Xinying Li,&nbsp;Chuyi Wu,&nbsp;Ming Zou","doi":"10.1007/s00277-026-07153-3","DOIUrl":"10.1007/s00277-026-07153-3","url":null,"abstract":"<div><p>This study investigates the relationship between hereditary protein S deficiency (PSD) and cerebral venous sinus thrombosis (CVST) through phenotypic and genetic analyses in a proband and family members with compound heterozygous <i>PROS1</i> mutations. A retrospective analysis was conducted on the clinical data of one patient diagnosed with CVST treated in The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University in July 2025. Peripheral venous blood samples were collected from the proband and 14 individuals from three generations, and relevant coagulation parameters and thrombin generation and inhibition assays were performed. Plasma protein S activity (PS: A), total protein S antigen (TPS: Ag), and free protein S antigen (FPS: Ag) were quantified. All exons and flanking regions of PROS1 were amplified by polymerase chain reaction (PCR) and analyzed by Sanger sequencing. Bioinformatics tools were used to evaluate mutation conservation, predict pathogenicity, and analyze structural effects on the protein. Thrombin generation and inhibition assays indicated defective anticoagulant function in the proband. The proband was diagnosed with CVST and type Ⅰ PSD (PS: A 39%, TPS: Ag 53 mg/L, FPS: Ag 42 mg/L). Genetic analysis identified a heterozygous missense variant c.1544G &gt; A (p.Arg515His) and a heterozygous synonymous mutation c.2001 A &gt; G (p.Pro667Pro) in the PROS1 gene. Arg515 was highly conserved across nine homologous species. The p.Arg515His mutation was predicted to be pathogenic and associated with reduced protein stability and abnormal folding. Compound heterozygous variants c.1544G &gt; A and c.2001 A &gt; G in the PROS1 gene may be associated with reduced protein S levels in this pedigree. The occurrence of CVST in the proband with PSD patients may also be related to these compound heterozygous variants.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"105 9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-026-07153-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389856","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}