Although research on palliative care in hematological malignancies has increased, research examining quality of death (QOD) and quality of care (QOC) in this population remains limited. This study compared QOD and QOC between patients with hematological malignancies and those with solid tumors. The authors conducted a secondary analysis of a nationwide mortality follow-up survey of bereaved family members in Japan (2017-2018). The study included 3575 decedents with hematological malignancies and 50,592 with solid tumors. Propensity score matching was performed to adjust for demographic and clinical characteristics. QOD and QOC were assessed using the Good Death Inventory (GDI) and the Care Evaluation Scale 2.0 (CES). Bivariate analyses compared the matched groups. Overall, QOD and QOC were comparable between groups. However, among the GDI subdomains, patients with hematological malignancies had slightly lower scores for "good relationships with family" (mean difference, 0.2; 95% confidence interval [CI], 0.03-0.3) and "preparation for death" (mean difference, 0.2; 95% CI, 0.04-0.3). In addition, patients with hematological malignancies were less likely to die in palliative care units than those with solid tumors (mean difference, 3.9%; 95% CI, 0.4%-7.4%). Although overall quality measures were similar, specific QOD domains related to family relationships and preparation for death were slightly lower among patients with hematological malignancies. These findings may reflect limited opportunities for end-of-life discussions due to the unpredictable and rapidly progressive course of hematological malignancies. Enhancing communication about prognosis and goals of care and early integration of palliative care may improve end-of-life experiences.
Pediatric oncological and hematological diseases remain a significant challenge due to their complexity, the need for personalized treatment, and long-term follow-up. Recent advances in medical technologies, particularly in information technology (IT), telemedicine, mobile health (mHealth), and precision medicine, have opened new possibilities for improving care and supporting clinical decision-making in pediatric patients. This quasi-systematic review examines the current landscape of emerging technologies applied in pediatric oncology and hematology. A structured literature search was conducted in MEDLINE (PubMed), Web of Science, Scopus, and Google Scholar between March and April 2024, covering studies published from January 2018 to February 2024. A total of 157 met the predefined inclusion criteria. A critical analysis was performed regarding the clinical utility, implementation readiness, and limitations of these technologies, with particular attention to developmental variability and pediatric-specific safety requirements. Telehealth and mHealth tools were identified as effective solutions to improve accessibility and continuity of care by enabling remote consultations, real-time monitoring, and enhanced patient and family engagement. Precision medicine approaches demonstrated improved progression-free survival in selected high-risk pediatric populations, while AI-based tools supported diagnostic and prognostic decision-making. Despite these advances, the overall evidence remains heterogeneous, with limited high-quality randomized trials and scarce long-term cost-effectiveness evaluations. Ethical, infrastructural, and economic barriers continue to affect widespread implementation. A multidimensional and system-oriented approach is required to effectively integrate innovative technologies into real-world pediatric oncology and hematooncology settings.
Caregivers of patients with cancer experience many emotional challenges. It is important for caregivers to cope with the difficult emotions they experience and to prepare for the grieving process. Nurses should support caregivers in managing negative experiences, crises, and difficult emotions. This study was conducted to determine the experiences of caregivers of individuals with hematological diagnoses. The study was designed using an Interpretive Phenomenological Analysis approach. Eighteen informal caregivers were recruited through purposive sampling. In-depth interviews were conducted using a semistructured interview form. According to the content analysis, 3 themes (Barbed wire, Dead end, Stairway to endurance) and 7 subthemes (Infection focus, Cage, Life in the shadow of care, Mask, Positive suggestion, Solidarity, Reliance on God) emerged. The themes reflect the development of empowerment and the challenges experienced by caregivers of individuals diagnosed with hematological cancer. Caregivers of patients with hematological cancer need support in navigating the emotional, physical, and social dimensions of their role. Oncology nurses play a crucial role in effective communication and process management between patients and caregivers.
To investigate the effects of deep hyperthermia on hematological parameters and tumor markers in patients with malignant tumors and to evaluate its potential adjuvant therapeutic value in improving hematopoietic and immune function. A retrospective analysis was conducted on 182 tumor patients who underwent deep hyperthermia at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine. A detailed deep hyperthermia treatment protocol, including tumor localization, temperature monitoring, treatment parameters and quality assurance, was strictly implemented. Hematological parameters and tumor markers were monitored dynamically during treatment. The Friedman test and a linear mixed-effects model were used for comparison and trend prediction. After deep hyperthermia treatment, the Neutrophil, White blood cell count, Red blood cell count, Lymphocyte, Hemoglobin, and Platelet count were significantly increased over time (p < 0.01). At Day 56, hemoglobin increased by 12.21% and lymphocytes increased by 27.48% compared to baseline. The levels of CA153, CA724, CA242, CA50 and SCCA decreased significantly (p < 0.01). In contrast, there was no significant change in CEA, CA125 and CA199 (p > 0.05). A linear mixed-effects model predicted continued improvement in hematological parameters until Day 70. Deep hyperthermia is associated with significantly improves hematological parameters and reduces specific tumor markers in cancer patients, with a favorable safety profile. It suggests potential benefits in enhancing immune function, correcting anemia, and reducing bleeding risk, and can serve as an effective adjuvant therapy for malignant tumors.
Data of various infections in febrile neutropenia (FN) in pediatric oncology patients in era of high burden of antimicrobial resistance (AMR) is lacking. This was a prospective observational study conducted in a pediatric oncology unit of a tertiary level dedicated oncology center from March 2025 to September 2025. We recruited patients with FN and studied antibiotic prescription patterns, microbiological data with relation to patient outcomes. Among the 122 FN episodes assessed, FN without microbiologically documented infection (MDI) or clinically documented infection (CDI) was observed in 66 cases (54.1%). FN with a CDI occurred in 35 cases (28.7%), while FN with a MDI was identified in 21 cases (17.2%). In our study 67% of FN episodes responded while on 1st line antibiotics and antibiotic escalation was required in 33% of episodes, out of which 1/3rd was targeted (i.e. based on culture) and in only 28 out of 122 (23%) episode was antibiotics escalated due to clinical reasons (hemodynamic compromise, new localization or persistent fever for >4 days). In 8 episodes (6.5%) hemodynamic instability was seen requiring intensive care unit (ICU) care and death occurred in 3 episodes. Prevalence of microbiology proven infection is low in FN in pediatric oncology settings and also that majority of the patients can be managed with 1st line antibiotics with only few requiring escalation to carbapenem and even fewer requiring escalation to last resort antibiotics.
Most novel anti-cancer therapies involve combining multiple immuno-oncology and/or targeted drugs. The historical paradigm of exploring combination regimens only after approval of the individual drugs is changing rapidly leading to clinical development of 'novel-novel' combination therapies consisting of at least two investigational agents. Initiating those combination efforts early in development is an important strategy to accelerate evolution of the standard of care for high unmet need cancer indications. However, there are specific challenges associated with such development programs, with additional complexity if more than one company is involved. Representing a consortium of major oncology drug developers, we critically discuss those challenges and suggest potential solutions to encourage the development of novel multi-company combination therapies for solid and hematological tumors. The areas covered include trial strategies for early and late clinical development, including dose/regimen optimization, statistical considerations, optimizing safety profiles, dose modification approaches, contribution of components, choice of standard of care backbone and comparator regimens as well as regulatory strategies.
This study aimed to analyze the clinical characteristics and rate of transfusion related adverse reactions (TRARs) in pediatric patients with malignant solid and hematological tumors. A retrospective analysis was conducted on 34,195 blood transfusions (RBC: 41.0%; PLT: 40.7%; FFP: 16.0%; cryoprecipitate: 2.3%) among 9,129 pediatric patients. TRARs were classified and severity graded according to the Chinese Haemovigilance Network criteria. Statistical comparisons were made between serious (n = 37) and non-serious (n = 194) TRAR cases. The overall TRAR rate was 680/100,000 (231/34,195), with PLT-associated TRARs being most frequent (1,250/100,000, 174/13,915). Allergic transfusion reactions (ATRs) dominated (95.7%, 221/231), followed by febrile non-hemolytic reactions (FNHTRs, 3.5%, 8/231). Serious TRARs (16.0%, 37/231) primarily involved ATRs (91.9%, 34/37), presenting with respiratory/gastrointestinal symptoms (41.2%) or anaphylactic shock (14.7%). After adjustment for multiple comparisons using the Bonferroni correction, prophylactic premedication was significantly associated with the occurrence of serious TRARs (p < 0.001). Pediatric patients with malignant solid and hematological tumors exhibit a high TRAR incidence, particularly with PLT transfusions. ATRs constitute the majority, underscoring the need for vigilant monitoring and evidence-based prophylaxis. The inefficacy of routine premedication raises important questions about tailored transfusion strategies. Further research is warranted to optimize platelet product selection and TRAR management protocols in this vulnerable population.
Chimeric antigen receptor (CAR) T-cell therapy has been investigated in neurological diseases, encompassing both central nervous system malignancies and autoimmune disorders, thereby extending its application beyond hematological cancers. This scoping review evaluates CAR T-cell therapy applications in neurological conditions, assessing therapeutic efficacy, safety profiles, and neurotoxicity management strategies. A literature search across four databases (January 2020-December 2025) identified 33 studies meeting the inclusion criteria, encompassing original and secondary research from international centers. CAR T-cell therapy demonstrated promising efficacy across diverse neurological conditions. In glioblastoma trials, 44% of patients (n = 128) achieved partial or complete clinical/radiographic responses with favorable safety profiles. Moreover, compelling results emerged from neuromyelitis optica spectrum disorder studies, in which 92% of patients (11/12) achieved sustained relapse-free remission over a median follow-up of 5.5 months. Multiple sclerosis, myasthenia gravis, and stiff-person syndrome cases exhibited excellent treatment tolerance without significant immune effector cell-associated neurotoxicity syndrome (ICANS), which is a major concern affecting 27% of patients with hematological malignancies. Overall, CAR T-cell therapy emerges as a novel therapeutic strategy in neurology, encompassing both oncological and autoimmune conditions. Toxicity profiles in neurological CAR T-cell applications differ substantially from those observed in hematologic malignancies, underscoring the need for condition-specific risk assessment frameworks and customized management approaches. Future research should prioritize larger multicenter trials with extended follow-up to establish definitive efficacy and safety profiles in neurological indications.
This study introduces a novel method for evaluating red blood cell (RBC) deformability using a microfluidic platform equipped with constriction channels that mimic capillary vessels. The normalized transit velocity of RBCs at 50% compression ratio (V^ε = 0.5) is proposed as a quantitative index of RBC deformability. Experimental validation is conducted in two key phases. First, to validate the proposed index, a controlled reduction in RBC deformability is induced using varying concentrations of diamide. V^ε = 0.5 progressively decrease as the diamide concentration increased, confirming that the index tracks changes in RBC deformability. Second, to demonstrate the ability of the platform to detect disease-specific properties, RBCs from patients with iron deficiency anemia (IDA), thalassemia (Thal), and hereditary spherocytosis (HS) are analyzed. The results reveal elevated deformability from IDA and Thal patients, and reduced deformability from HS patients. High V^ε = 0.5 values consistently correlate with RBC characteristics known to enhance deformability-such as thin, elliptical morphology, a high surface-area-to-volume ratio, and low internal viscosity-whereas lower values are associated with characteristics that impair deformability. These findings highlight the impact of RBC characteristics on deformability and the importance of our microfluidic platform as a robust tool for investigating hematological diseases.
Chimeric antigen receptor T-cell (CAR-T) therapy has become an established treatment for hematological malignancies. Lymphodepleting (LD) chemotherapy is a preparatory step that facilitates CAR-T cell expansion and persistence. While fludarabine and cyclophosphamide (Flu/Cy) are a standard LD regimen, bendamustine has emerged as a potential alternative. We performed a systematic review and meta-analysis comparing the efficacy and safety of bendamustine versus Flu/Cy as LD regimens. We systematically searched PubMed, Scopus, and the Cochrane Central Register of Controlled Trials from inception to July 2025. Nine retrospective studies comprising 768 patients were included. The bendamustine cohort demonstrated a lower incidence of all-grade cytokine release syndrome (CRS) compared with Flu/Cy (60.2% vs. 71.7%; p = 0.011), whereas no difference was observed in grade ≥ 3 CRS. Overall infections were less frequent with bendamustine (18.3% vs. 53.7%; p < 0.001). There were no significant differences between groups in the incidence of immune effector cell-associated neurotoxicity syndrome, overall response rate, overall survival, and progression-free survival. Bendamustine LD therapy significantly reduced the incidence of all-grade CRS and overall infections without compromising CAR-T efficacy. These findings suggest that bendamustine may serve as a viable alternative LD regimen.
Apilimod is an emerging therapeutic compound whose clinical potential has renewed interest in the PIKfyve signaling pathway, a central regulator of endolysosomal trafficking and cellular homeostasis. This review provides a critical overview of the current state of knowledge on Apilimod, spanning early mechanistic studies, preclinical models, and ongoing phase II clinical trials. Apilimod primarily inhibits PIKfyve, leading to profound alterations in vesicular trafficking and vacuolization. Beyond its canonical role in endosomal dynamics, accumulating evidence implicates PIKfyve in broader biological processes, including immune regulation and metabolic control, thereby expanding the potential therapeutic relevance of its pharmacological targeting. Preclinical and clinical studies have suggested possible applications of Apilimod in inflammatory diseases, hematological malignancies, and solid tumors. However, despite encouraging initial findings, important uncertainties remain regarding its precise mechanisms of action, context-dependent efficacy, and safety profile. In particular, the translatability of preclinical observations to clinical benefit, the identification of predictive biomarkers, and the management of potential adverse effects require further investigation. Finally, we discuss emerging therapeutic strategies, including combination approaches with RAS pathway inhibitors, while highlighting the key challenges that must be addressed to fully exploit the therapeutic potential of Apilimod.
GATA1 and GATA2 are zinc-finger transcription factors essential for normal hematopoiesis. As genetic testing becomes more widely integrated into clinical practice, GATA1/2-related disorders are increasingly recognized, making it important for clinicians to understand their diagnosis and management. This review summarizes the clinical features, disease mechanisms, and management considerations for GATA1- and GATA2-related hematological disorders. We discuss germline GATA1 mutations causing rare X-linked erythroid and megakaryocytic cytopenias, somatic GATA1 mutations driving myeloid leukemia of Down syndrome, and germline GATA2 mutations causing GATA2 deficiency syndrome-a predisposition to immunodeficiency and myeloid malignancies affecting up to 75%-80% of carriers. Evolving genotype-phenotype patterns, the somatic mutational landscape, and current therapeutic strategies, including allogeneic hematopoietic stem cell transplantation (HSCT), are reviewed. Despite growing recognition of GATA1/2-related disorders, many aspects of disease biology and clinical variability remain incompletely understood. Earlier identification and risk stratification of affected patients, along with advances in transplant approaches and novel therapeutics, will be essential for improving outcomes. The authors have confirmed clinical trial registration is not needed for this submission.
This study aimed to develop and validate a novel model for predicting mortality risk in cancer patients with carbapenem-resistant organism (CRO) infections. Cancer patients with CRO infections in Henan Cancer Hospital between January 2022 and March 2024 were included in this retrospective study. LASSO regression was used to construct a novel model for predicting mortality in cancer patients with CRO infections. Receiver operating characteristic (ROC), decision curve analysis (DCA), and clinical impact curves (CIC) were used to assess the predictive ability and clinical utility of the prediction model. A total of 417 cancer patients with CRO infections were included in the study. Fourteen factors were selected, including sample source, radiotherapy, blood culture, exposure to antibiotics after susceptibility testing, lymphocyte-to-monocyte ratio (LMR), lymphocyte-to-monocyte ratio (LMR), total protein (TP), blood urea nitrogen (BUN), calcium (CA), C-reactive protein (CRP), triglyceride (TG), procalcitonin (PCT), prothrombin time (PT), and thrombin time (TT), which were found to be associated with 30-day mortality in cancer patients with CRO infections. The areas under the ROC curve for the prediction model were 0.815 (95% CI: 0.767-0.857) and 0.801 (95% CI: 0.716-0.871) for the primary cohort and validation cohort, respectively. The models demonstrated good predictive accuracy, with p-values 0.479 and 0.786 on the Hosmer-Lemeshow test. DCA and CIC analyses confirmed the clinical utility of the prediction model. Our model could be used as an effective individualized risk prediction tool for clinicians. It would provide personalized risk assessments for cancer patients with CRO infections.
Insulin Receptor Substrate 1 (IRS1) is differentially expressed in hematological neoplasms suggesting a role in hematopoiesis and neoplastic transformation. Irs1 knockout mice represent a tool to investigate IRS1 function. This study compared hematological parameters of wild-type and heterozygous Irs1S57X mice and assessed fetal lethality in homozygous mice. Hematological parameters were analyzed monthly in wild-type and heterozygous mice from 8 to 22 weeks of age. Successive intercrosses failed to yield homozygous knockouts. Fetal lethality was evaluated through timed matings of heterozygous mice, with genotyping performed at various gestational stages (E9.5, E12.5, E15.5 and E18.5). Heterozygous mice showed no significant differences in body weight or hematological parameters compared with wild-type mice (all p-value >0.05). Homozygous Irs1S57X mice exhibited fetal or postnatal lethality as fetuses developed until gestational stage E18.5 but were either aborted or died shortly after birth. The Irs1S57X mutation in heterozygosis does not alter phenotype, whereas homozygosity for Irs1S57X is associated with markedly reduced perinatal survival, precluding adult hematopoiesis studies. Future research should focus on fetal hematopoiesis.
Leptomeningeal metastasis (LM) is common in patients with lung adenocarcinoma, leading to high mortality rates. The predictors of systematic survival in patients with LM and lung adenocarcinoma remain poorly understood. The present study retrospectively analyzed 78 lung adenocarcinoma patients with or without LM treated at Ningbo Medical Center, Lihuili Hospital (Ningbo, China) between November 2016 and August 2024. Clinical characteristics and baseline hematological parameters obtained at LM diagnosis were evaluated for their associations with overall survival (OS). Median OS was 9.0 months (range: 0.2-48.9 months) in patients with LM. Univariate analysis identified age <60 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, receipt of brain radiotherapy after a diagnosis of LM, no extracranial metastasis, epidermal growth factor receptor (EGFR) 19 mutation, receipt of third-generation EGFR tyrosine kinase inhibitor therapy before a diagnosis of LM, neutrophil-to-lymphocyte ratio <7.5755, platelet-to-lymphocyte ratio (PLR) <156.035 and a molecular graded prognostic assessment >1.5 to be significant predictors of superior OS. According to multivariate analysis, extracranial metastasis [hazard ratio (HR)=2.291; 95% CI, 1.074-4.888; P=0.032], PLR <156.035 (HR=0.233; 95% CI, 0.123-0.442; P<0.001) and ECOG PS 0-2 (HR=0.302; 95% CI, 0.152-0.599; P=0.001) remained predictive of OS. In conclusion, extracranial metastasis, PLR and ECOG PS were identified to be prospective independent clinical prognostic indicators of survival in patients with lung adenocarcinoma and LM. Overall, the present study highlighted the potential use of clinical characteristics and hematological variables before treatment to predict the outcomes of patients with lung adenocarcinoma complicated with LM.
Ovarian Cancer (OC), the deadliest gynecological malignancy, poses a major therapeutic challenge in advanced stages owing to its high recurrence rate and metastatic potential. In this regard, it is noteworthy that immunotherapy has recently gained significant attention in OC treatment, a phenomenon attributable to notable advances in over-the-counter Chimeric Antigen Receptor (CAR)-based cell therapy. At the heart of CAR-T Cell (CAR-T) immunotherapy is genetically modified CAR molecules that enable immune cells to target and recognize tumor antigens. Based on such strategies, CAR-T therapies have developed rapidly in hematological oncology and are gradually being extended to solid tumors. Despite their potential in OC treatment, several factors, including off-target effects attributable to the lack of Tumor-Specific Antigens (TSAs), as well as severe side effects such as tumor immune barriers, Cytokine Release Syndrome (CRS), and neurotoxicity, have been established to limit the clinical use of CAR-T therapies. Moreover, compared to CAR-T, CAR-Natural Killer (NK) and CAR-Macrophage (M) therapies have distinct advantages. The killing mechanism of NK cells integrates both CAR-dependent and non-dependent pathways, avoiding severe CRS and neurotoxicity. Furthermore, besides directly phagocytosing tumors due to its strong ability to infiltrate tumors, CAR-M therapy could also effectively improve the Immunosuppressive Microenvironment (IME) via immunomodulatory factor secretion to remodel M2-type Tumor-Associated Macrophages (TAMs) into the M1 phenotype with anti-tumor function. In this review, we systematically describe the research progress in CAR-T therapy for OC and compare the similarities and differences of three types of cellular therapies (CAR-T, CAR-NK, and CAR-M) regarding their mechanisms of action, clinical advantages, and technological bottlenecks. We hope that our findings will provide a theoretical basis for optimizing immunotherapeutic strategies for OC. Trial Registration: ClinicalTrials.gov identifier: NCT03585764.
Pediatric oncological emergencies are acute, life-threatening complications arising from malignancies or their treatment. Prompt recognition and intervention are essential to prevent significant morbidity and mortality. Pediatric oncological emergencies are categorized as metabolic, structural, hematological, or treatment-related. Structural emergencies include superior mediastinal syndrome, spinal cord compression, and raised intracranial pressure. Metabolic complications such as tumor lysis syndrome (TLS) and hypercalcemia are frequent, with TLS most common in leukemias and high-grade lymphomas. Hematological crises, hyperleukocytosis with leukostasis, and severe cytopenias may result in bleeding or infections. Treatment-related complications like febrile neutropenia and neutropenic enterocolitis (NEC) add further challenges. Effective management requires a multidisciplinary approach that combines early diagnosis, vigilant monitoring, supportive measures, and disease-directed therapy. Recent progress in risk stratification, early warning systems, and intensive supportive care has improved the ability to anticipate and mitigate these crises. Novel diagnostic tools, including point-of-care ultrasonography (POCUS) and laboratory markers, allow for faster identification of high-risk patients, while updated management guidelines provide evidence-based strategies for intervention. This review highlights novel insights and recent updates in the recognition and management of pediatric oncological emergencies.
An increasing number of reports showed patients with bulky tumors after lattice radiation therapy (LRT) treatment achieved good local control. However, in these reports, LRT was previously used primarily for palliation. We reported a case that LRT plays a synergistic role in the radical treatment of locally advanced bulky cervical cancer (LABCC) combined with INTERLACE study protocol. The patient was a 54-year-old female with LABCC and treated with LRT combined with the INTERLACE study protocol. She received three fractions of 3 Gy each to the gross tumor volume (GTV) and three fractions of 9 Gy each to the lattice therapy volume (LTV), on an emergent basis, using volumetric modulated arc therapy (VMAT). Subsequently, according to the INTERLACE study protocol, chemotherapy and radiotherapy were carried out and the standard follow-up examinations were conducted. Adverse events (AEs) were assessed according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. The patient initially received LRT, which reduced the tumor burden and controlled bleeding. After this was combined with the INTERLACE study protocol, the complete clinical response (cCR) was achieved and they maintained this status for 13 months after the completion of concurrent chemoradiotherapy (CCRT), with only manageable grade IV hematological toxicity observed after the completion of CCRT. During this period, only manageable grade IV hematological toxicity (platelet count 16 × 109/L, white blood cell count 0.33 × 109/L) was observed. In this case, LRT combined with INTERLACE study protocol appears to be a safe and effective for the treatment of LABCC which improved the patient's quality of life without uncontrolled treatment-related toxicity.
Chimeric antigen receptor T (CAR-T) cell therapy has achieved transformative success in hematological malignancies; however, its translation to solid tumors remains severely limited by tumor heterogeneity, immunosuppressive microenvironments, and safety concerns such as on-target/off-tumor toxicity. A major contributor to these challenges is the lack of preclinical models capable of faithfully recapitulating human tumor architecture and tumor-immune interactions. Conventional two-dimensional cell cultures and animal models frequently fail to predict CAR-T efficacy, resistance, and toxicity observed in patients. Organoid technology, particularly patient-derived organoids (PDOs) and immune-integrated organoid systems, has emerged as a next-generation platform that bridges this translational gap. By preserving patient-specific genetic, phenotypic, and spatial heterogeneity, organoids provide a physiologically relevant and scalable system for interrogating CAR-T cell behavior in human-like tumor contexts. Recent advances in tumor-immune co-culture, vascularized organoids, and microfluidic organoid-on-a-chip platforms have further expanded their utility for dynamic assessment of CAR-T infiltration, cytotoxicity, cytokine release, and adaptive resistance mechanisms. In this review, we comprehensively examine how organoid-based models are reshaping the CAR-T development pipeline, spanning target discovery and validation, functional efficacy assessment, safety profiling, and optimization of combination therapies. We further discuss emerging applications of organoids as patient-specific "avatars" for personalized CAR-T selection and response prediction. Finally, we highlight current technical limitations and future bioengineering directions required to enable clinical translation. Collectively, organoid platforms represent a transformative tool for accelerating precision development of next-generation CAR-T cell therapies and advancing human-relevant immuno-oncology research.
Typ515 (W515) mutations in the protein MPL are one of key driver mutations promoting BCR/ABL-negative myeloproliferative neoplasms (MPNs), but their effects on hematopoietic stem cells (HSCs) and MPN-related hematological abnormalities have not been studied in physiological contexts. Here, we established a MplW514L knock-in mouse model which largely mimics human MPLW515L mutation during hematopoiesis. The mutant mice developed an essential thrombocythemia (ET)-like MPN phenotypes, displaying excess megakaryopoiesis and thrombocytosis and progressive myelofibrosis. Mechanistically we observed that MplW514L-conditioned HSC compartment had a unique disease-initiating capacity however it did not exhibit a obvious advantage of competitive repopulation over wild-type control. Notably, single-cell analysis and flow cytometry profiles support that MplW514L expression led to a significant expansion of megakaryocyte-biased stem cell fate within the HSC pool. Finally, JAK2 inhibitor treatment phenotypically alleviated the ET signs but failed to eliminate the disease-initiating HSCs. These findings underscore the etiology of physiological expression of MPLW515L mutation in HSCs, and also provide a valuable in vivo model to evaluate potential therapeutic options for patients with MPLW515L-positive MPN.