Annals of Hematology最新文献

{"title":"Advances in epigenetic therapies for B-cell non-hodgkin lymphoma","authors":"Weiwen Hu,&nbsp;Lanlan Zang,&nbsp;Xiaoxi Feng,&nbsp;Shuhui Zhuang,&nbsp;Liudi Chang,&nbsp;Yongjing Liu,&nbsp;Jinyan Huang,&nbsp;Yuanyuan Zhang","doi":"10.1007/s00277-024-06131-x","DOIUrl":"10.1007/s00277-024-06131-x","url":null,"abstract":"<div><p>B-cell non-Hodgkin lymphomas (B-NHLs) constitute a varied group of cancers originating from B lymphocytes. B-NHLs can occur at any stage of normal B-cell development, with most arising from germinal centres (e.g. diffuse large B-cell lymphoma, DLBCL and follicular lymphoma, FL). The standard initial treatment usually involves the chemoimmunotherapy regimen. Although there is a high initial response rate, 30–40% of high-risk patients often face relapsed or refractory lymphoma due to drug resistance. Recent research has uncovered a significant link between the development of B-NHLs and various epigenetic processes, such as DNA methylation, histone modification, regulation by non-coding RNAs, and chromatin remodeling. Therapies targeting these epigenetic changes have demonstrated considerable potential in clinical studies. This article examines the influence of epigenetic regulation on the onset and progression of B-NHLs. It discusses the current therapeutic targets and agents linked to these epigenetic mechanisms, with the goal of offering new perspectives and approaches for targeted therapies and combination chemotherapy in treating B-NHLs.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"103 12","pages":"5085 - 5101"},"PeriodicalIF":3.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational heterogeneity in large B-cell lymphoma: insights from paired biopsies.","authors":"Ditte Stampe Hersby, Lone Schejbel, Marie Fredslund Breinholt, Estrid Høgdall, Peter Nørgaard, Torsten Holm Nielsen, Lars Møller Pedersen, Anne Ortved Gang","doi":"10.1007/s00277-024-06108-w","DOIUrl":"https://doi.org/10.1007/s00277-024-06108-w","url":null,"abstract":"<p><strong>Introduction: </strong>Large B-cell lymphoma (LBCL) exhibits striking clinical and molecular heterogeneity. New approaches have emerged to explore tumor heterogeneity and classify LBCL into biological categories. Consequently, the informational requirements from diagnostic samples to provide the necessary information have increased, but the adequacy of single-site biopsies to provide such information is largely unknown. Here we describe spatial and temporal intra-patient variations in the mutational landscape of paired biopsies.</p><p><strong>Methods: </strong>Paired biopsies from 30 patients with LBCL were obtained from spatially distinct sites at the time of primary diagnosis before treatment and/or at a subsequent relapse. The samples were sequenced using a custom designed 59-gene next generation sequencing (NGS) lymphoma panel.</p><p><strong>Results: </strong>Differences in detected mutations of pathogenic or likely pathogenic significance were frequent both when comparing paired diagnostic biopsies, 2/6 (33%), and when comparing paired biopsies at primary diagnosis and relapse, 8/16 (50%). Mutational heterogeneity tended to increase with longer time interval between biopsies. Analysis of paired diagnostic and relapse biopsies revealed that certain clones present at diagnosis disappeared, while new clones emerged at relapse. Notably, TP53 mutations were detected in six out of seven patients in an extranodal location. In two cases, TP53 mutation was only detected in the relapse biopsy. Several of the mutations identified in this study are used or under investigation as targets for cancer treatments.</p><p><strong>Conclusion: </strong>Multi-site biopsies revealed spatial and temporal mutational heterogeneity in patients with LBCL. Our findings indicate that mutational differences between biopsy pairs can occur at all timepoints examined. This underscores the necessity of performing repeat biopsies with each relapse to capture the full spectrum of genetic aberrations.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Livedoid vasculopathy in hemoglobinopathy-associated chronic leg ulcers","authors":"Harish Eswaran,&nbsp;Samuel Wilson,&nbsp;Jane Little,&nbsp;Stephan Moll","doi":"10.1007/s00277-024-06112-0","DOIUrl":"10.1007/s00277-024-06112-0","url":null,"abstract":"<div><p>Chronic leg ulceration is a debilitating manifestation of hemoglobinopathies, and best management is uncertain. Livedoid vasculopathy (LV) is a cutaneous non-inflammatory thrombotic vasculopathy treated with anticoagulation that has been identified in hemoglobinopathy-associated chronic leg ulceration. However, most patients with hemoglobinopathy-associated ulcers do not undergo workup for secondary causes, and the prevalence and relevance of LV is unclear. Outcomes of secondary workup were examined retrospectively in this study. 108 patients with hemoglobinopathy-associated chronic leg ulcers were identified. 15% of patients underwent skin biopsy, and 97% of biopsies showed non-specific findings. Two patients had LV and neither responded to anticoagulants. Livedoid vasculopathy is a rare cause of ulceration in hemoglobin gene disorders and the benefit of anticoagulation in these cases is unclear.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"103 12","pages":"5235 - 5239"},"PeriodicalIF":3.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-reported outcome domains in multiple myeloma randomized controlled trials and association with survival outcomes.","authors":"Darshi Shah, Francesco Sparano, Catherine Luo, Daniela Krepper, Johannes M Giesinger, Thomas Baldi, Eilidh Duncan, Madeline Pe, Rajshekhar Chakraborty, Fabio Efficace","doi":"10.1007/s00277-024-06129-5","DOIUrl":"https://doi.org/10.1007/s00277-024-06129-5","url":null,"abstract":"<p><p>Patient-reported outcomes (PROs) are crucial endpoints in multiple myeloma (MM) randomized controlled trials (RCTs), yet there is significant variability in their methodology and reporting. Our study aimed to (a) identify the most commonly pre-specified PRO domains in MM RCTs and those most responsive to modern therapies, and (b) examine the association between PROs and progression-free survival (PFS)/overall survival (OS). We performed a systematic review of MM RCTs that used EORTC QLQ-C30 and published between 01/2014-06/2023. The association between PFS/OS and PRO was explored using Fisher's exact test or Pearson's Chi-squared test. Thirty-five RCTs were identified, with PROs as secondary or exploratory endpoints in all studies. About one-third of RCTs (n=11, 31.4%) pre-specified at least one EORTC QLQ-C30 domain, with the most common domains being Global health status/Quality of life (GHS/QoL) (n = 10, 90.9%), Physical Functioning (n = 6, 54.5%), Fatigue (n = 6, 54.5%), and Pain (n = 6, 54.5%). A statistically significant and/or clinically meaningful difference in at least one EORTC QLQ-C30 domain between arms was seen in 23/35 trials (65.7%), with the most common domains showing improvement being GHS/QoL (12/23 trials), Pain (11/23 trials), Fatigue (9/23 trials), and Physical Functioning (9/23 trials). PRO was noted to be concordant with PFS in 19/33 (57.6%) trials (p = 0.398), and with OS in 22/31 (71%) trials (p = 0.018). Our study identified key PRO domains that can be potentially used as primary endpoint in MM RCTs. Additionally, significant association between PROs and OS highlight the importance of integrating PROs to better capture treatment efficacy.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival impact of hypoxia-inducible factor-1 alpha (HIF-1α) in Nucleophosmin1 mutated acute myeloid leukemia","authors":"Chantiya Chanswangphuwana,&nbsp;Narittee Sukswai,&nbsp;Nichthida Tangnuntachai,&nbsp;Ponlapat Rojnuckarin","doi":"10.1007/s00277-024-06124-w","DOIUrl":"10.1007/s00277-024-06124-w","url":null,"abstract":"<div><p><i>Nucleophosmin1</i> (<i>NPM1</i>) mutated acute myeloid leukemia (AML) without <i>FLT3</i>-ITD mutation is classified as a favorable risk AML which responds well to cytarabine therapy. Hypoxia-inducible factor-1 alpha (HIF-1α) promotes leukemic cell survival and maintains leukemic stem cell quiescence possibly contributing to cytarabine resistance. This study evaluated HIF-1α expression using immunohistochemistry in bone marrow of 29 newly diagnosed <i>NPM1</i>^<b>+</b><i>FLT3</i>-ITD^<b>−</b> normal karyotype AML patients and analyzed its correlation with survival. All patients achieved complete remission after standard induction chemotherapy and proceeded to cytarabine consolidations. Positive HIF-1α staining with golgi body pattern and strong cytoplasmic HIF-1α expression was identified in 34.5% and 58.6% of patients, respectively. The expression of golgi body or strong cytoplasmic HIF-1α expression was related to increased relapse (<i>p</i> = 0.048) with significantly inferior relapse-free survival (RFS, <i>p</i> = 0.042). Using multivariate analysis, extramedullary disease at diagnosis was revealed as an independent prognostic factor for adverse RFS (hazard ratio [HR] 3.82; 95% confidence interval [CI] 1.26–11.55, <i>p</i> = 0.018), while golgi body or strong cytoplasmic HIF-1α expression showed a trend toward poor RFS (HR 3.56; 95% CI 1.00–12.69, <i>p</i> = 0.050). In summary, high HIF-1α expression is potentially a baseline prognostic biomarker for poor RFS and cytarabine resistance in <i>NPM1</i>^<b>+</b><i>FLT3</i>-ITD^<b>−</b> AML. Further studies with the large number of patients are warranted.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"103 12","pages":"5417 - 5423"},"PeriodicalIF":3.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-024-06124-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765359","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 girl with a novel nonsense mutation in Chediak-Higashi syndrome was relieved successfully by treatment with HCST and UCBT: a case report.","authors":"CanLiu, Aijun Zou, Xianyu Wang, Qiang Yu","doi":"10.1007/s00277-024-06039-6","DOIUrl":"10.1007/s00277-024-06039-6","url":null,"abstract":"<p><p>Chediak-Higashi syndrome (CHS) is a life-threatening autosomal recessive immunodeficiency disease presenting with recurrent infections, hypopigmentation, progressive neurodegeneration, and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated stage. Two-thirds of patients experience a fatal accelerated phase. CHS is caused by lysosomal transport regulator (LYST) gene mutations. We report the case of CHS, who was born with pale skin and silver hair. Bone marrow aspirate revealed large inclusions in granulocytes, monocytes, and lymphocytes. Genetic analysis revealed a new nonsense mutation in the LYST gene: c.8186G > A (W2729Ter). The child presented with fever, hepatosplenomegaly, and lymphadenectasis. Laboratory tests showed pancytopenia, hypofibrinogenemia, and high serum ferritin, indicating an accelerated phase of CHS. She underwent allogeneic hematopoietic stem cell transplantation (HCST) combined with umbilical cord blood transplantation (UCBT) after HLH-related chemotherapy. The patient has been alive for nine months without recurrence. We have identified a novel nonsense mutation in the LYST gene that correlates with a severe phenotype, and HSCT combined with UCBT is an effective treatment.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"5957-5961"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A brisk peripheral T-cell reaction following rituximab treatment for follicular lymphoma.","authors":"Cristina Frusteri, Isacco Ferrarini","doi":"10.1007/s00277-024-05931-5","DOIUrl":"10.1007/s00277-024-05931-5","url":null,"abstract":"<p><p>Bone marrow reactive T-cell infiltrates have been frequently observed in patients affected by follicular lymphoma after rituximab treatment. In some studies, bone-marrow T-cell expansion has been associated with an effective anti-tumor response and favorable prognosis. In this manuscript, we report on a particularly brisk CD4⁺ T-cell reaction occurring after rituximab treatment for follicular lymphoma and involving the peripheral blood in addition to the bone marrow. Peripheral blood T-cell reaction was mainly composed of effector-memory CD4⁺ T cells and may reflect the expansion of an effective anti-tumor immunity.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"6035-6037"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roxadustat combined with immunosuppressants for treatment of pure red cell aplasia with kidney injury.","authors":"Lulu Fan, Lujia Cao, Yangyan Luo, Fang Gao","doi":"10.1007/s00277-024-06053-8","DOIUrl":"10.1007/s00277-024-06053-8","url":null,"abstract":"<p><p>Pure red cell aplasia is a rare condition that may be congenital or associated with an underlying disease.Immunosuppressants are a commonly employed therapeutic option for the treatment of pure red cell aplasia;however, they are associated with considerable adverse effects, including nephrotoxicity. This case report describesa 74-year-old patient with pure red cell aplasia who developed long-term kidney injury following cyclosporinetherapy. Renal anemia is a common complication after chronic kidney injury and contributes to the poor outcome ofanemia treatment. Following a series of medication adjustments, the final treatment with roxarestat combined withsirolimus proved effective in delaying the impairment of this patient's kidney function, with the hemoglobin levelremaining above 100 g/L throughout. This case report demonstrates the efficacy of roxarestat in conjunction with animmunosuppressive agent in the treatment of pure red cell aplasia combined with kidney injury, with a dual effect ofalleviating the anemia and reducing serum creatinine levels.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"5925-5927"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study.","authors":"Naokazu Nakamura, Nobuyoshi Arima, Teruhito Takakuwa, Satoshi Yoshioka, Kazunori Imada, Kentaro Fukushima, Masaaki Hotta, Shin-Ichi Fuchida, Junya Kanda, Nobuhiko Uoshima, Yuji Shimura, Hirokazu Tanaka, Kensuke Ohta, Satoru Kosugi, Hideo Yagi, Satoshi Yoshihara, Ryosuke Yamamura, Yoko Adachi, Hitoshi Hanamoto, Hirohiko Shibayama, Naoki Hosen, Tomoki Ito, Chihiro Shimazaki, Akifumi Takaori-Kondo, Junya Kuroda, Itaru Matsumura, Masayuki Hino","doi":"10.1007/s00277-024-05705-z","DOIUrl":"10.1007/s00277-024-05705-z","url":null,"abstract":"<p><p>Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"5681-5690"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plerixafor in association with R-DHAP and G-CSF to mobilize a large number of CD34 + cells in patients with relapsed-refractory diffuse large B-cell lymphomas.","authors":"Francesco Gaudio, Anna Mele, Eleonora Prete, Filomena Emanuela Laddaga, Alessandro Maggi, Nicola Di Renzo, Giuseppe Milone, Angelo Ostuni, Vincenzo Pavone","doi":"10.1007/s00277-024-06103-1","DOIUrl":"10.1007/s00277-024-06103-1","url":null,"abstract":"<p><p>Lymphoma and plasma cell disorders are the most common indications for autologous hematopoietic stem cell (HSC) transplantation. We conducted a prospective multicenter study with the aim of testing the feasibility of plerixafor (PLX) in combination with R-DHAP and G-CSF in 37 patients with relapsed refractory diffuse large B-cell lymphoma (R/R DLBCL) in order to collect a large number of HSC with a goal of transplantation. After R-DHAP, daily monitoring of peripheral blood CD34 + cells by flow cytometry was performed starting on day + 13. If, on day + 14, peripheral blood CD34 + cells were > 20 × 10e6/L apheresis was started, if they were < 20 × 10e6/L and WBC > 4.0 × 10e9/L, PLX was administered. Results: The median CD34 + cell count collected was 10.5 × 10e6/kg (range 0-51). 81% of patients achieved the minimum CD34 + target cell count of 6 × 10e6/kg. 66% of patients required only one apheresis to achieve collection goals. The rate of engraftment was 10 days for neutrophils > 0.5 × 10e9/L and 13 days for platelets > 20 × 10e9/L. In conclusion, the addition of PLX to salvage therapy in patients with R/R DLBCL is effective and may be routinely used in the future to increase the number of CD34 + cells collected and minimize the risk of poor mobilization.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"5799-5805"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}