Leukemia Research Reports最新文献

{"title":"T cell dysfunction associated with repeated CAR-T cell manufacturing failure following prolonged bispecific antibody exposure: a case report","authors":"Skylar J.W. Henry,&nbsp;Kirsten Pfeffer,&nbsp;Kevin G. Shim,&nbsp;Erin W. Meermeier,&nbsp;Fan Feng,&nbsp;Julia E. Wiedmeier,&nbsp;Saurabh Chhabra,&nbsp;P. Leif Bergsagel,&nbsp;Rafael Fonseca,&nbsp;Alex M. Wonnaparhown,&nbsp;Michael P. Gustafson","doi":"10.1016/j.lrr.2026.100611","DOIUrl":"10.1016/j.lrr.2026.100611","url":null,"abstract":"<div><h3>Overview</h3><div>We describe a patient with two consecutive manufacturing failures after prolonged bispecific antibody treatment in which longitudinal immune phenotyping and functional assays were performed to investigate potential mechanisms.</div></div><div><h3>Background</h3><div>CAR-T cell therapy and bispecific antibodies (BsAb) have significantly improved outcomes in relapsed/refractory multiple myeloma (r/rMM), yet the optimal treatment sequence remains unclear, particularly regarding the impact of prior BsAb exposure on downstream CAR-T manufacturability.</div></div><div><h3>Case Presentation</h3><div>A 72-year-old man with r/rMM had two CAR-T cell manufacturing failure events following multiple therapies including an FcRL5 × CD3 bispecific antibody. Both collections yielded an insufficient CAR-T cell dose. Longitudinal immune phenotyping revealed markers of T cell dysfunction, including loss of CCR7, CD27, and CD28, alongside severely impaired TCR-driven proliferation with preserved interleukin-2 responsiveness.</div></div><div><h3>Conclusion</h3><div>These findings link profound T cell dysfunction with repeated CAR-T cell manufacturing failures and suggest that pre-leukapheresis immune phenotyping may identify patients at risk for manufacturing failure.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"26 ","pages":"Article 100611"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged, transplant-free remission with tagraxofusp in combination with venetoclax for transplant-ineligible blastic plasmacytoid dendritic cell neoplasm","authors":"Tia Cheunkarndee,&nbsp;Claire Schumann,&nbsp;Naveen Pemmaraju,&nbsp;Gabriel Mannis","doi":"10.1016/j.lrr.2026.100614","DOIUrl":"10.1016/j.lrr.2026.100614","url":null,"abstract":"<div><div>Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy predominantly affecting older adults. While the CD123-directed agent tagraxofusp has improved outcomes, durable long-term survival is typically limited to patients eligible for transplant, leaving effective transplant-free treatment strategies as an urgent unmet need. Here, we report the case of an 84-year-old woman with concurrent Rai stage 0 chronic lymphocytic leukemia (CLL) who presented with skin-limited BPDCN and was treated with tagraxofusp and venetoclax combination therapy. The patient achieved a clinical complete remission exceeding four years, with only mild capillary leak syndrome during cycle one of tagraxofusp as well as intermittent grade 1 neutropenia as toxicities. To our knowledge, this represents the longest reported duration of tagraxofusp-based therapy in BPDCN. This outcome aligns with emerging evidence supporting synergy between CD123-targeted therapies and BCL2 inhibition, including recent data from a tagraxofusp-azacitidine-venetoclax triplet regimen demonstrating improved outcomes compared to tagraxofusp monotherapy. This case suggests that combination therapy strategies may enable prolonged, transplant-free remission in BPDCN, a finding of particular significance given the older, often transplant-ineligible population disproportionately affected by this disease.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"26 ","pages":"Article 100614"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149153587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized comparison of CPX-351 and FLAG-Ida in high-risk myelodysplastic syndrome: A subgroup analysis of UK NCRI AML19","authors":"Priyanka Mehta,&nbsp;Tomas Skacel,&nbsp;Stefan Faderl,&nbsp;Roderick Murphy,&nbsp;Saemi Park,&nbsp;Abin Thomas,&nbsp;Sean Johnson,&nbsp;Alex Legg","doi":"10.1016/j.lrr.2026.100609","DOIUrl":"10.1016/j.lrr.2026.100609","url":null,"abstract":"<div><div>CPX-351 improves outcomes for patients with secondary acute myeloid leukemia, but evidence of its use in high-risk myelodysplastic syndromes (MDS) is limited. This exploratory subgroup analysis of the randomized, controlled, open-label, phase 3 study—UK NCRI AML19—compared outcomes with CPX-351 versus FLAG-Ida in patients with high-risk MDS, to provide insights into the potential role of CPX-351 in this population. A total of 57 patients were included (CPX-351, n = 34; FLAG-Ida, n = 23). Compared with FLAG-Ida, CPX-351 prolonged median overall survival (OS; 17.8 vs 10.8 months) and median relapse-free survival (19.1 vs 7 months). Hematopoietic cell transplantation (HCT) rate was 59% and 52% for CPX-351 and FLAG-Ida, respectively. Median OS post-HCT was longer with CPX-351 than FLAG-Ida (22.3 vs 11.6 months). CPX-351 had a lower rate of serious adverse events than FLAG-Ida (9%vs 61%). These findings suggest that CPX-351 may be a promising frontline treatment option for high-risk MDS, and warrant confirmation in prospective studies.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"26 ","pages":"Article 100609"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149153589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD20 antibody–based combination therapy may reduces the adverse prognostic impact of M-protein positivity in marginal zone lymphoma","authors":"Yajun Zhang,&nbsp;Wanqian Hu,&nbsp;Ying Fang,&nbsp;Bo Zheng,&nbsp;Yi Zhang,&nbsp;Wenda Chen,&nbsp;Rong Li","doi":"10.1016/j.lrr.2026.100616","DOIUrl":"10.1016/j.lrr.2026.100616","url":null,"abstract":"<div><h3>Background</h3><div>Monoclonal M-protein is frequently detected in marginal zone lymphoma (MZL) and has been historically associated with adverse clinical features. Its prognostic value in the era of modern immunotherapy remains unclear.</div></div><div><h3>Patients and methods</h3><div>We retrospectively analyzed 43 patients with MZL, comparing clinical characteristics, treatments, and outcomes between patients with and without M-protein. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier analysis, and prognostic factors were evaluated by Cox regression.</div></div><div><h3>Results</h3><div>M-protein was detected in 39.5% of patients and was associated with higher tumor burden, worse performance status, and elevated inflammatory and biochemical markers. However, no significant differences in PFS or OS were observed between groups, and M-protein was not an independent prognostic factor. Most patients received contemporary CD20 antibody–based combination therapies.</div></div><div><h3>Conclusion</h3><div>In the setting of modern treatments, M-protein positivity may not confer an adverse prognostic impact in MZL.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"26 ","pages":"Article 100616"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149199165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning models in predictive factors for megaloblastic character of macrocytic anemia","authors":"Melek Kechida ,&nbsp;Mohamed Kenani ,&nbsp;Nader Slama ,&nbsp;Manel Mili ,&nbsp;Aminetou Salem ,&nbsp;Wassim Krit ,&nbsp;Ines Khochtali ,&nbsp;Sarra Boukhris ,&nbsp;Asma Ben Abdallah ,&nbsp;Mohamed Hedi Bedoui","doi":"10.1016/j.lrr.2026.100568","DOIUrl":"10.1016/j.lrr.2026.100568","url":null,"abstract":"<div><h3>Background</h3><div>Differentiating megaloblastic from non-megaloblastic macrocytic anemia usually relies on vitamin B12 and/or B9 assessment and bone marrow examination. In resource-limited regions, these diagnostic tools are not readily available. This study aims to develop a machine learning model to distinguish between these two forms of macrocytic anemia using commonly accessible clinical and laboratory parameters.</div></div><div><h3>Methods</h3><div>A logistic regression model was developed using a dataset containing clinical features and routine laboratory data. Key predictive variables were identified through the SequentialFeatureSelector. The model was optimized using GridSearchCV and validated through stratified 5-fold cross-validation to ensure robust performance.</div></div><div><h3>Results</h3><div>ESR, glossitis, and MCHC were the most influential variables in predicting non-megaloblastic anemia, with respective importance percentages of 23.11 %, 22.07 %, and 13.87 %. Other variables such as LDH (13.77 %), aregenerative status (13.42 %), and limb paresthesia (11.78 %) also contributed significantly to the model, while MCV had a comparatively lower importance (1.98 %). The model demonstrated a high discriminatory ability, with an area under the ROC curve (AUC) of 0.92 and an overall accuracy of 94 %. Learning curve analysis confirmed its stability and consistent performance across varying data sizes.</div></div><div><h3>Conclusions</h3><div>By reducing dependence on specialized diagnostic tests and invasive procedures, this approach is particularly suited for resource-constrained healthcare settings.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100568"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147395027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival predictors in Vietnamese elderly AML patients treated with decitabine: Real-world evidence from a low- and middle-income country","authors":"Ha Thanh Nguyen ,&nbsp;Quoc Khanh Bach ,&nbsp;Quoc Nhat Nguyen ,&nbsp;Van Nam Nguyen ,&nbsp;Thi Van Anh Nguyen ,&nbsp;Hai Pham-The","doi":"10.1016/j.lrr.2026.100565","DOIUrl":"10.1016/j.lrr.2026.100565","url":null,"abstract":"<div><h3>Background</h3><div>Hypomethylating agents such as decitabine represent a key treatment option for elderly acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. However, real-world evidence from low- and middle-income countries (LMICs), including Vietnam, remains scarce. This study aimed to identify baseline clinical and laboratory predictors of 1-year overall survival (OS) in elderly Vietnamese AML patients treated with decitabine.</div></div><div><h3>Methods</h3><div>This prospective, single-center, observational study was conducted at the National Institute of Hematology and Blood Transfusion, Vietnam, from April 2023 to June 2025. Seventy newly diagnosed AML patients aged ≥ 60 years received decitabine. The primary outcome was 1-year OS. Baseline demographic, clinical, hematologic, and immunophenotypic variables were analyzed using univariate and multivariate Cox regression. Treatment response was descriptively evaluated in patients completing ≥4 cycles.</div></div><div><h3>Results</h3><div>The 1-year OS rate was 38.6 %, with a median survival of 276.0 days. Elevated bone marrow cell count (HR: 1.003, <em>p</em> = 0.002), fibrinogen (HR: 1.22, <em>p</em> = 0.044), and urea (HR: 1.23, <em>p</em> = 0.001) were independently associated with increased mortality. CD64 positivity (HR: 0.29, <em>p</em> = 0.029) and urban residence (HR: 0.43, <em>p</em> = 0.014) were protective. Among 39 patients completing ≥4 cycles, 48.7 % achieved a complete response. No significant survival difference was observed between responders and non-responders.</div></div><div><h3>Conclusion</h3><div>This first prospective real-world study in Vietnam identified accessible predictors of survival in elderly AML patients receiving decitabine. The findings may aid early risk stratification using simple baseline parameters in LMIC settings, where access to molecular diagnostics may be limited, and warrant multicenter validation.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100565"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatitis induced by Peg-aspargase in children: a real-world pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS)","authors":"Wenwen Zhang ,&nbsp;Bin Luo ,&nbsp;Zhuo Liu ,&nbsp;Jie Mi ,&nbsp;Yanping Yang ,&nbsp;Yuan Li","doi":"10.1016/j.lrr.2026.100562","DOIUrl":"10.1016/j.lrr.2026.100562","url":null,"abstract":"<div><div>This study analyzed FAERS data to evaluate pegaspargase safety in pediatric acute lymphoblastic leukemia treatment. Among 21,161,817 reports, 847 identified pegaspargase as the primary suspect drug, revealing adverse events (AEs) across 26 organ systems. Disproportionality analysis identified four previously unlisted AEs. Critically, pegaspargase-associated pancreatitis incidence showed significant age-dependence (χ²=8.219, <em>p</em> &lt; 0.05). These findings address the knowledge gap in real-world, long-term pediatric safety profiles and provide crucial clinical references for safer medication use in children.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100562"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bruton tyrosine kinase inhibitors in combination with chemoimmunotherapy is an effective treatment for patients with Richter’s syndrome","authors":"Tristan Meier ,&nbsp;Giovann Huynh ,&nbsp;Ernesto Ayala ,&nbsp;Han W. Tun ,&nbsp;Madiha Iqbal","doi":"10.1016/j.lrr.2026.100564","DOIUrl":"10.1016/j.lrr.2026.100564","url":null,"abstract":"<div><div>Richter’s syndrome (RS) is characterized by transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into an aggressive lymphoma. While significant treatment advances have been made in the management of CLL/SLL, current front-line management of RS is consistent with chemoimmunotherapy (CIT), a therapeutic approach adopted from the management of de-novo diffuse large B-cell lymphoma (DLBCL). In de-novo DLBCL, CIT alone can potentially cure a significant percentage of patients; however in RS, outcomes with CIT alone are particularly poor. Therefore there is a significant unmet need to improve the current standard of care for the management of RS. We present a case of a patient with newly diagnosed RS who was treated with a novel upfront combination of CIT and a Bruton tyrosine kinase inhibitor, resulting in excellent long-term outcomes. We also present accompanying literature review highlighting other anecdotal cases reported with similar therapeutic approach and discuss emerging treatment strategies in the management of RS.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100564"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gilteritinib-associated hand-foot syndrome: a novel dermatologic reaction in refractory FLT3 Acute myeloid leukemia","authors":"Jack T. Seki ,&nbsp;Jad Sibai ,&nbsp;Maria Agustina Perusini ,&nbsp;Hassan Sibai","doi":"10.1016/j.lrr.2026.100585","DOIUrl":"10.1016/j.lrr.2026.100585","url":null,"abstract":"<div><div>Objective: Second generation tyrosine kinase inhibitors (TKIs) such as gilteritinib, characterized by minimal EGFR and absent VEGFR inhibition, are in theory associated with low dermatologic toxicity. This case report brings to the awareness that the opposite may occur and emphasize the need for attentive pharmacovigilance.</div><div>Methods: An elderly woman presented to us with relapsed/refractory (R/R) FLT3-ITD AML following azacytidine treatment, received single-agent TKI gilteritinib, selected for its greater potency and specificity. Unexpectedly, she developed a severe hand-foot skin lesion requiring treatment interruption.</div><div>Results: After receiving two cycles of gilteritinib 120mg orally daily without therapeutic response, the dose was escalated to 200mg in accordance with RCT guidelines. After one week, the patient developed dry skin and mild erythema of the hands and feet, which progressed to a severe hand-foot syndrome the following week.</div><div>Conclusion: This unprecedented adverse event reporting suggests that the FLT3-specific TKI gilteritinib can induce cutaneous toxicities, through dose-dependent inhibition of proangiogenic pathways.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100585"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147746695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emphasizing the diagnostic and management challenge: Nodular sclerosis Hodgkin lymphoma with pericardial infiltration in an adolescent male - A case report","authors":"Saja I. AbuGhannam ,&nbsp;Celina R. Andonie ,&nbsp;Leen I. Masalmeh ,&nbsp;Akram Karama ,&nbsp;M.Ziad Alresheq ,&nbsp;Aliaa’ khalili","doi":"10.1016/j.lrr.2026.100596","DOIUrl":"10.1016/j.lrr.2026.100596","url":null,"abstract":"<div><div>Hodgkin’s lymphoma is a malignancy of lymphoid tissue with a generally favorable prognosis; however, symptomatic initial presentation with pericardial involvement is rare and presents significant diagnostic and therapeutic challenges. We report the case of a previously healthy 17-year-old male who presented with a four-month history of progressive cough and exertional dyspnea, along with a newly noticed right supraclavicular mass, without systemic B symptoms. Transthoracic echocardiography demonstrated a mild pericardial effusion, and subsequent PET-CT imaging revealed findings consistent with advanced disease. An excisional biopsy of the lymph node confirmed the diagnosis of nodular sclerosis classical Hodgkin lymphoma, and the patient was staged as Stage IV due to both pulmonary and pericardial involvement. Initial cytoreductive treatment with COP (Cyclophosphamide, Vincristine, Prednisone) was administered, followed by standard ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) chemotherapy. This case illustrates the importance of including lymphoproliferative disorders in the differential diagnosis of pericardial effusion. Furthermore, it emphasizes the importance of early imaging, histopathological confirmation, and a multidisciplinary approach in guiding appropriate treatment strategies. As this can help prevent severe complications and enhance the patient's prognosis.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100596"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148183636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}