Chimeric antigen receptor T-cell (or CAR-T) therapy and bispecific antibodies (BsAbs) have revolutionized the treatment of hematologic malignancies, offering new options for relapsed or refractory cases. However, these therapies carry risks of early complications, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and delayed issues like graft-versus-host disease (GVHD), infections, and secondary cancers. Effective management requires early diagnosis using advanced biomarkers and imaging, along with prompt interventions involving immunosuppressants, corticosteroids, and cytokine inhibitors. A multidisciplinary approach is essential, integrating hematologists, oncologists, and infectious disease specialists, with emerging strategies like targeted biologics and personalized medicine showing promise in balancing efficacy with toxicity management. Ongoing research is critical to refine diagnostics and treatments, ensuring that these therapies not only extend survival but also improve patients’ quality of life. This review provides critical insights for healthcare professionals to quickly recognize and treat complications of CAR-T and BsAbs therapies. By focusing on early detection through biomarkers and imaging and outlining timely therapeutic interventions, it aims to equip the multidisciplinary care team with the knowledge necessary to manage the challenges of these advanced treatments effectively, ultimately optimizing patient outcomes.

Adoptive cell therapies have transformed the treatment landscape for hematologic malignancies. Yet, translation to solid tumors remains constrained by antigen heterogeneity, an immunosuppressive tumor microenvironment (TME), and poor persistence of conventional CAR-T cells. In response, innate immune cell platforms, particularly chimeric antigen receptor–engineered natural killer (CAR-NK) cells and chimeric antigen receptor–macrophages (CAR-MΦ), have emerged as promising alternatives. This review summarizes recent advances in the design and application of CAR-NK and CAR-MΦ therapies for solid tumors. We highlight key innovations, including the use of lineage-specific intracellular signaling domains (e.g., DAP12, 2B4, FcRγ), novel effector constructs (e.g., NKG7-overexpressing CARs, TME-responsive CARs), and scalable induced pluripotent stem cell (iPSC)-derived platforms. Preclinical data support enhanced antitumor activity through mechanisms such as major histocompatibility complex (MHC)-unrestricted cytotoxicity, phagocytosis, trogocytosis, cytokine secretion, and cross-talk with adaptive immunity. Early-phase clinical studies (e.g., CT-0508) demonstrate feasibility and TME remodeling with CAR-MΦ. However, persistent challenges remain, including transient in vivo survival, manufacturing complexity, and risks of off-target inflammation. Emerging combinatorial strategies, such as dual-effector regimens (CAR-NK⁺ CAR-MΦ), cytokine-modulated cross-support, and bispecific or logic-gated CARs, may overcome these barriers and provide more durable, tumor-selective responses. Taken together, CAR-NK and CAR-MΦ platforms are poised to expand the reach of engineered cell therapy into the solid tumor domain.

The gut microbiota plays a critical role in maintaining gastrointestinal homeostasis, immune regulation, and metabolic processes. Recent evidence has highlighted its significant influence on gastric carcinogenesis. Helicobacter pylori, a well-established class I carcinogen, remains the most prominent microbial risk factor for gastric cancer. However, emerging studies indicate that alterations in the broader gastric and intestinal microbial communities, referred to as dysbiosis, may also contribute to tumor initiation, progression, and immune evasion. These microbial shifts can lead to chronic inflammation, genotoxic metabolite production, and modulation of signaling pathways such as NF-κB and Wnt/β-catenin. This review explores the current understanding of the gut microbiome’s contribution to gastric cancer pathogenesis, including microbial signatures associated with precancerous lesions and the tumor microenvironment. Furthermore, the potential of microbiota-based biomarkers and therapeutic interventions, including probiotics, prebiotics, and fecal microbiota transplantation, is discussed as part of emerging precision medicine strategies.

Background: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Methods: Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. Results: In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. Conclusion: Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.

Graft-versus-host disease (GVHD) remains a significant barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), contributing to long-term morbidity and non-relapse mortality in both pediatric and adult populations. Central to GVHD pathophysiology is the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, where JAK2 mediates key pro-inflammatory cytokines, including IL-6, IFN-γ, and GM-CSF. These cytokines promote donor T cell activation, effector differentiation, and target organ damage. The introduction of ruxolitinib, a selective JAK1/2 inhibitor, has transformed the treatment landscape for steroid-refractory acute and chronic GVHD, leading to improved response rates and durable symptom control. However, its limitations—such as cytopenias, infectious complications, and incomplete responses—have catalyzed the development of next-generation agents. In 2024, the FDA approved axatilimab, a CSF-1R inhibitor that targets monocyte-derived macrophages in fibrotic chronic GVHD, and remestemcel-L, an allogeneic mesenchymal stromal cell therapy, for pediatric steroid-refractory acute GVHD. Both agents offer mechanistically distinct and clinically meaningful additions to the therapeutic armamentarium. In parallel, emerging combination strategies involving JAK2 inhibitors and novel biologics show promise in enhancing immune tolerance while preserving graft-versus-leukemia (GvL) effects. Recent advances in biomarker development, such as the MAGIC Algorithm Probability (MAP), are enabling early risk stratification and response prediction. The integration of these tools with organ-specific and personalized approaches marks a shift toward more precise, durable, and tolerable GVHD therapy. This review highlights the current state and future direction of JAK2 inhibition and complementary therapies in the evolving GVHD treatment paradigm.

Hematologic malignancies, including acute myeloid leukemia, myelodysplastic syndromes, lymphoma, and multiple myeloma, are characterized by profound biological heterogeneity and highly dynamic treatment trajectories that conventional, static prognostic systems incompletely capture. Cellular therapies, such as chimeric antigen receptor T-cell therapy and hematopoietic stem cell transplantation, offer potentially curative options for relapsed or refractory disease, yet outcomes remain highly variable, and management decisions regarding conditioning intensity, lymphodepletion, immunosuppression, and toxicity surveillance continue to be largely protocol-driven rather than individually adapted. Artificial intelligence (AI) and machine learning (ML) have demonstrated substantial promise in diagnostic support, prognostic stratification, and multimodal data integration across hematologic malignancies, but existing models remain predominantly static and related to pre-treatment in orientation, limiting their utility for real-time clinical guidance. This review summarizes current AI applications in hematologic oncology; critically compares the strengths, limitations, and clinical applicability of major AI model classes, including traditional machine learning, deep learning, multimodal integrative frameworks, reinforcement learning, digital twins, and emerging foundation models and large language models; and proposes an adaptive, multimodal paradigm. We examine key enabling technologies and address the clinical, regulatory, ethical, and implementation challenges that must be resolved before these systems can be deployed at the bedside. We argue that the central challenge facing the field is no longer whether AI can predict outcomes, but whether it can actively guide real-time therapeutic decisions, and that achieving this transition will require interdisciplinary collaboration, prospective validation, and governance frameworks capable of ensuring interpretability, equity, and clinical trustworthiness.