Yangmin Zhu

The past decade has witnessed a paradigm shift in the treatment of hematologic malignancies, driven by the emergence of T-cell redirecting immunotherapy. Chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs) have revolutionized the outcomes of patients with relapsed or refractory B-cell lymphomas, leukemias, and multiple myeloma. However, the rapid clinical adoption of these sophisticated modalities has outpaced our ability to definitively compare them, select optimal candidates, and manage their distinctive toxicity profiles. This Research Topic assembles original research, systematic reviews, and clinical case reports that collectively illuminate the current state of these therapies and chart a course for their optimal integration into clinical practice.The comparative effectiveness of CAR-T and BsAbs represents a central clinical question. He et al. provided the largest meta-analysis addressing this in relapsed/refractory follicular lymphoma, demonstrating superior complete response rates (82% vs. 65%) and progression-free survival with CAR-T therapy, although at the cost of increased neurotoxicity. Multivariate analysis revealed that CAR-T was not an independent predictor of response after adjusting for confounders, suggesting that patient-and disease-specific factors, including tumor burden, prior treatment refractoriness, and disease stage, significantly influenced outcomes. This nuanced finding challenges the notion of universal superiority and emphasizes the importance Diagnostic precision is equally important to therapeutic efficacy. Ibraheem and Dalby addressed the critical need to distinguish cytokine release syndrome from sepsis, a clinical dilemma that frequently complicates CAR-T management. The DRACARYS study protocol proposes the IL-6/procalcitonin ratio as a bedside biomarker to guide appropriate interventions. This study exemplifies the evolution from efficacy-focused clinical trials to supportive care optimization, recognizing that toxicity management is integral to therapeutic success and that accurate diagnosis prevents both unnecessary immunosuppression and inappropriate antibiotic exposure.A comprehensive review by Arimokhtari and Lutfi synthesizes the pivotal trials that led to FDA approvals for hematologic malignancies while examining resistance mechanisms and next-generation constructs. The long-term follow-up from CARTITUDE-1, demonstrating that one-third of multiple myeloma patients remain progression-free at five years, provides compelling evidence that CAR-T may offer curative potential in this previously incurable disease. The review also critically examines novel approaches-armored CAR-T, in vivo CAR-T, allogeneic CAR-T, and dual-targeting strategies-that aim to overcome current limitations, including Tcell exhaustion, antigen escape, and logistical barriers.Collectively, this Research Topic establishes that CAR-T and BsAbs are not competing therapies but rather complementary tools within an evolving therapeutic armamentarium. The optimal strategy requires an individualized risk-benefit assessment considering patient fitness, disease kinetics, treatment urgency, and prior therapy exposure. CAR-T offers superior efficacy at the cost of greater toxicity and logistical complexity, whereas BsAbs provide accessible, off-the-shelf options with favorable safety profiles but potentially less durable responses. Future research should prioritize head-to-head randomized trials with biomarker stratification, optimized sequencing strategies, and toxicity mitigation in high-risk populations. As these immunotherapies expand beyond hematology into solid tumors and autoimmune diseases, the lessons learned from this collection will inform broader applications, ultimately improving outcomes across the spectrum of immune-mediated diseases.The integration of these powerful modalities into thoughtful and personalized treatment pathways represents the next frontier in cancer immunotherapy.

Background Treatment-free remission (TFR) is a new long-term goal for treating selected patients with chronic myeloid leukemia in the chronic phase (CML-CP). Still, the appropriate group in which TFR can be attempted and the factors influencing it have not yet been identified. This meta-analysis aimed to explore TFR in CML-CP patients who achieved a deep molecular response (DMR) before Tyrosine kinase inhibitors (TKIs) discontinuation and to explore possible factors influencing TFR and the safety of discontinuation. Methods We performed a systematic review and single-arm meta-analysis with a systematic search of published literature up to September 2023 in PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases. The assessment was performed using the MINORS scale. Random-effects models were used to calculate outcome metrics, including overall mean TFR rates at 12 and 24 months and subgroup differences. Data synthesis and analysis were done by Stata17.0 software. Results A total of 19 single-arm trials involving 2336 patients were included in this meta-analysis, with an overall mean TFR rate of 59% [95CI:0.56–0.63] at 12 months and 55% [95CI:0.52–0.59] at 24 months, and no CML-related deteriorations or deaths reported during the TFR period. Our subgroup analysis showed that better TFR was associated with prior interferon therapy (P = 0.003), and molecular response depth MR5.0 (P = 0.020). Conclusion Our study demonstrated that prior interferon therapy and attainment of a molecular response depth of MR5.0 or greater were associated with higher TFR rates, with patients who attained MR5.0 or greater achieving a TFR rate of up to 62% in the second year after TKI discontinuation. Considering the high heterogeneity of the included trials, the above influences still require further validation and more detailed subgroup analysis in future discontinuation trials. Systematic review registration: https://www.crd.york.ac.uk/prospero/ (Registration No. CRD42023471334).

Targeted therapy for acute myeloid leukemia (AML) is an effective strategy, but currently, there are very limited therapeutic targets for AML treatment. Ferroptosis is strongly related to drug resistance and carcinogenesis. However, there are few reports about ferroptosis in AML. This article explores the relationship between ferroptosis-related gene (FRG) expression and prognosis in AML patients from the FerrDb and the Cancer Genome Atlas (TCGA) databases. The ferroptosis-related gene ARNTL was observed to have high expression and poor prognosis in AML. Receiver operating characteristic curve (ROC) analysis revealed the predictive accuracy of the signature. The area under the time-dependent ROC curve (AUC) was 0.533 at one year, 0.619 at two years, and 0.622 at three years within the training cohort. Moreover, we found that the ARNTL expression is closely associated with tumor-infiltrating immune cells like the macrophages and NK cells. Inhibiting the ARNTL expression suppressed colony formation and induced ferroptosis in AML cells. Overall, the survival prediction model constructed based on ARNTL accurately predicted the survival in AML patients, which could be a potential candidate for diagnosing and treating AML.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is most frequently used to treat acute myeloid leukemia (AML). Whether patients should routinely receive consolidation chemotherapy before proceeding to transplant after achieving first complete remission (CR1) has been a subject of debate. We performed a systematic review and meta-analysis of studies examining the impact of post-remission chemotherapy before allo-HSCT in patients with AML in CR1. Six studies including 1659 patients were included in the meta-analysis. The pooled hazard ratio (HR) for overall survival was 0.9 (95% confidence interval [CI] 0.77–1.05, P = 0.182), and the pooled HR for leukemia-free survival was 0.87 (95% CI 0.75–1.0, P = 0.07). No survival advantage was observed for post-remission chemotherapy before reduced-intensity conditioning or myeloablative conditioning (MAC) allo-HSCT for AML in CR1. The pooled relative risk for relapse incidence (RI) was 1.02 (95% CI 0.82–1.28, P = 0.834). Post-remission chemotherapy before allo-HSCT did not significantly affect the RI in patients with AML in CR1. The analyses revealed no significant benefit of post-remission consolidation chemotherapy in patients who received allo-HSCT. We recommend proceeding to allo-HSCT as soon as CR1 is attained.

We report two cases of rituximab (RTX)-induced interstitial pneumonia in two lymphoma patients receiving RTX treatment. Interstitial pneumonia was successfully managed in these two cases after a one-week-long intervention with corresponding treatments without affecting further treatment of the primary disease. RTX-induced interstitial pneumonia is characterized by a latent onset with an unclear pathological mechanism and absence of typical symptoms. High-resolution CT scan can provide valuable evidence for early diagnosis of RTX-induced interstitial pneumonia, which might be attributed partially to an increased susceptibility to P. jirovecii and fungal infection due to prolonged RTX treatment.

To investigate the clinical characteristics, outcomes and prognostic factors of primary bone lymphoma (PBL). We retrospectively analyzed 31 consecutive patients with the diagnosis of PBL initially treated at our hospital between 1992 and 2010. Kaplan-Meier method was used for survival analysis and Cox regression model used for analyzing the prognostic factors. The median age of the patients was 46 years. The most common sites of involvement were the femur (29%) and the spine (29%). Sixteen (52%) patients underwent chemoradiotherapy, and the other 15 (48%) received chemotherapy. With a median follow-up of 49 months, the patients showed an overall response rate of 94% (including a complete response rate of 68% and a partial response rate of 26%). The median overall survival (OS) of the patients was 71 months (95% CI: 36-106 months) with a median progression-free survival (PFS) of 47 months (95% CI: 30-64 months). Univariate analysis identified the use of rituximab, radiotherapy, and an international prognostic index (IPI) score of 0-2 as the favorable prognostic factors for OS and PFS. Multivariate analysis showed that the use of rituximab and IPI score were independent prognostic factors of the OS and PFS, and radiotherapy was the predicting factor for PFS but not for OS. The use of rituximab can improve the OS or PFS of patients with PBL, and radiotherapy offers additional benefits for PFS but not for OS.