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Purpose: This study aimed to examine the impact of high-risk cytogenetic abnormalities (HRA) on the survival outcomes of multiple myeloma patients with extramedullary disease (EMD) in the era of novel agents, utilizing the largest dataset of extramedullary multiple myeloma patients in China., Methods: This study included a total of 371 patients with EMD, comprising 113 patients with de novo EME and 258 patients with EMB., Results: Patients with one HRA and those with ≥ 2 HRA demonstrated significantly worse overall survival (OS) (P < 0.01) and progression-free survival (PFS) (P < 0.01) compared to patients without HRA. Additionally, 1q21 gain/amplification (1q21 +) remained a predictor of poor prognosis in EMD. CD38 monoclonal antibody-based therapy and single transplantation were less effective in improving survival outcomes for EMD with ≥ 2 HRA. Multivariable analysis identified LDH levels > 250 U/L, creatinine levels > 177 μmol/L, extramedullary extraosseous (EME), 1 HRA, and ≥ 2 HRA as independent adverse prognostic factors in patients with EMD., Conclusion: Patients with EMD who had ≥ 2 HRA experienced an extremely poor prognosis, which could not be improved by single transplantation or CD38 monoclonal antibody-based treatment. The number of HRA could serve as an important factor in guiding treatment choices and predicting prognosis in patients with EMD. Furthermore, 1q21 + remained a significant factor associated with worse survival outcomes in EMD., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by Institutional Ethical Review Board of Sun Yat-Sen university cancer center. Informed consent requirements were also waived by Institutional Ethical Review Board of Sun Yat-Sen university cancer center. The International Conference on Harmonization's Good Clinical Practice standards and the 1964 Helsinki Declaration and its later revisions served as the foundation for the study's methodology. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: The prognosis of extra-nodal NK/T cell lymphoma (ENKTL) is poor, and the optimal therapy remains controversial. This study aims to evaluate the safety and efficacy of a new combined modality therapy., Methods: Phase-2 study of pegaspargase, etoposide and gemcitabine (PEG) combined with involved field radiation therapy (IFRT) in newly-diagnosed patients with early-stage ENKTL. Patients received 4 course of PEG followed by IFRT. The primary endpoints were complete response (CR), partial response (PR), and objective response rate (ORR) after IFRT. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events., Results: 34 consecutive patients with Ann Arbor stage I/II were enrolled. 3 patients progressed on PEG, while the remaining 31 received IFRT. The ORR was 88.2% (30/34), included 28 (82.4%) complete and 2 (5.8%) partial responses. With a median follow-up of 56.0 months (Interquartile Range [IQR], 36.0-66.9 months), the estimated 5-year PFS and OS were 87.4% (95% Confidence Interval [CI],69.5%-94.8%) and 97.1% (95%CI, 80.1%-99.6%), respectively. Most adverse events were hematological and easily managed., Conclusions: PEG followed by IFRT is a safe and effective initial therapy for early-stage ENKTL, demonstrating impressive PFS and OS rates. This promising approach warrants further validation in a randomized controlled trial (Registered at Clinicaltrials.gov NCT02705508). Trial registration: ClinicalTrials.gov identifier: NCT02705508.

Background: Double-expressor diffuse large B-cell lymphoma (DE-DLBCL) has a poor prognosis, and optimal treatment strategies remain unclear. This study evaluates the efficacy and safety of RCHOP, R2-CHOP (RCHOP plus lenalidomide), and RCHOP plus Bruton's Tyrosine Kinase inhibitors (BTKi) in DE-DLBCL treatment., Methods: Data from 213 DE-DLBCL patients treated from January 2019 and February 2024. Among them, 112 received R-CHOP, 65 received R2-CHOP, and 36 received R-CHOP plus BTKi. We evaluated clinical characteristics, overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) for each groups., Results: Baseline characteristics were comparable across groups. ORRs were 95.5 % for R-CHOP, 96.9 % for R2-CHOP, and 97.2 % for R-CHOP plus BTKi, with CR rates of 76.5 %, 80 %, and 75 %, respectively. BTKi significantly improved PFS (p=0.033) but not affect OS (p=0.165). Lenalidomide showed no benefit in PFS (p=0.153) or OS (p=0.351). With median follow-up times of 20.6 months for R-CHOP, 23.5 months for R2-CHOP, and 17.6 months for R-CHOP plus BTKi, the 1-year PFS rates were 73.6 %, 82.2 %, and 93.3 %, and the 1-year OS rates were 96.2 %, 93.2 %, and 100 %, respectively. Grade 3-4 adverse events included leukopenia, neutropenia, and anemia, and thrombocytopenia, with no significant differences among groups., Conclusion: The addition of BTK inhibitor enhances progression-free survival in DE-DLBCL, especially in advanced-stage patients, without introducing new severe adverse reactions. In contract, adding lenalidomide does not offer additional efficacy or survival benefits., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In the era of novel agents, the clinical outcomes of induction treatment and the impact of the number of high-risk cytogenetic abnormalities (HRA) in newly diagnosed multiple myeloma (NDMM) need to be explored., Objective: Through this study, we aim to analyze the effectiveness of different induction treatments and explore the survival outcomes of patients with varying numbers of HRA., Methods: A total of 734 patients from seven medical centers were included in our study., Results: Patients in the CD38 monoclonal antibody or IMiDs plus proteasome inhibitors (PI) groups had significantly superior overall survival (OS) and progression-free survival (PFS) compared to those receiving IMiDs or PI alone. Additionally, the CD38 monoclonal antibody conferred a PFS advantage over IMiDs plus PI. Patients with ≥ 2 high-risk cytogenetic abnormalities (HRA) exhibited an extremely poor prognosis and should be considered ultra-high-risk individuals in multiple myeloma (MM). The CD38 monoclonal antibody, transplantation, and achieving minimal residual disease (MRD) negativity only partly mitigated the poor prognosis in patients with HRA. Furthermore, patients with 1q21 gain/amplification (1q21+) only had a significantly worse prognosis compared to patients without HRA, and those with 1q21+ plus del17p or t(4;14) exhibited an inferior prognosis compared to those with 1q21+ alone., Conclusion: Our results suggested that double-hit multiple myeloma was associated with extremely poor survival outcomes, and more effective treatments needed to be explored for this particular subtype of MM., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Bortezomib, lenalidomide, and dexamethasone (VRD), and bortezomib, doxorubicin, and dexamethasone (PAD), are commonly used in induction regimens for patients with newly diagnosed multiple myeloma (NDMM) in China. This real-world study enrolled 390 patients, 195 receiving VRD and 195 receiving PAD induction. The primary endpoint was progression-free survival (PFS) and stringent complete remission/complete remission. Across the entire cohort, VRD demonstrated significantly improved five-year overall survival (OS) (74% vs. 59%, p = 0.0024) and five-year PFS (67% vs. 37%, p = 0.0018) compared to PAD. Notably, the median OS and PFS were not reached for VRD-treated patients, while they were 77 months (60-not reached [NR]) and 46 months (36-NR), respectively, for PAD. In patients with standard-risk cytogenetics, VRD showed superior five-year OS (83% vs. 58%, p = 0.0038) and PFS (78% vs. 48%, p = 0.0091) compared to PAD. However, these differences were not statistically significant in high-risk patients. For transplanted patients, VRD was associated with superior five-year OS (91% vs. 67%, p = 0.014) and PFS (79% vs. 47%, p = 0.015) compared to PAD. In non-transplanted patients, VRD showed a trend towards improved five-year OS (p = 0.085) and PFS (p = 0.073) compared to the PAD group. In conclusion, VRD displayed superior OS and PFS outcomes in standard-risk patients and those who underwent transplantation. These findings suggest potential advantages of VRD over PAD in real-world clinical settings for NDMM treatment. However, due to the imbalance in transplantation rates between the VRD and PAD groups, limitations in testing for high-risk cytogenetic abnormalities (HRA), and the difference between the received cycles and salvage therapies, the conclusions of this study should be interpreted with caution., (© 2024. The Author(s).)

Introduction: Although there is extended research on the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in adult cancer patients (ACP), the immunogenicity to the variants of concern (VOCs) in childhood cancer patients (CCP) and safety profiles are now little known., Methods: A prospective, multi-center cohort study was performed by recruiting children with a solid cancer diagnosis and childhood healthy control (CHC) to receive standard two-dose SARS-CoV-2 vaccines. An independent ACP group was included to match CCP in treatment history. Humoral response to six variants was performed and adverse events were followed up 3 months after vaccination. Responses to variants were compared with ACP and CHC by means of propensity score-matched (PSM) analysis., Results: The analysis included 111 CCP (27.2%, median age of 8, quartile 5.5-15 years), 134 CHC (32.8%), and 163 ACP (40.0%), for a total 408 patients. Pathology included carcinoma, neural tumors, sarcoma, and germ cell tumors. Median chemotherapy time was 7 (quartile, 5-11) months. In PSM sample pairs, the humoral response of CCP against variants was significantly decreased, and serology titers (281.8 ± 315.5 U/ml) were reduced, as compared to ACP ( p < 0.01 for the rate of neutralization rate against each variant) and CHC ( p < 0.01 for the rate of neutralization against each variant) groups. Chemotherapy time and age (Pearson r ≥ 0.8 for all variants) were associated with the humoral response against VOCs of the CHC group. In the CCP group, less than grade II adverse events were observed, including 32 patients with local reactions, and 29 patients had systemic adverse events, including fever ( n = 9), rash ( n = 20), headache ( n = 3), fatigue ( n = 11), and myalgia ( n = 15). All reactions were well-managed medically., Conclusions: The humoral response against VOCs after the CoronaVac vaccination in CCP was moderately impaired although the vaccine was safe. Age and chemotherapy time seem to be the primary reason for poor response and low serology levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, Chen, Wang, Zhu, Liu, Zhang, Zhong, Fu, Wang, Cao, Bai, Wang, Chen, Wei, Lv, Zhang and Wang.)

Background: Cancer-related cognitive decline is a serious problem in long-term survival but no pivotal study has investigated whether checkpoint inhibitors (ICI) may be associated with cognitive adverse events., Methods: This propensity score-matched analysis recruited non-small cell lung cancer (NSCLC) patients prescribed with or without ICI monotherapy from three Chinese tertiary hospitals. Patients were excluded from study who developed brain metastasis or had disorders severely affecting cognitive abilities. Primary outcomes were changes in neuropsychological battery test (NBT) at baseline, 6- and 12-month sessions, and any NBT score changes that exceeded 3∗SD of baseline scores would be marked as objective cognitive adverse events (CoAE). Secondary endpoint was the 20-item Perceived Cognitive Impairment (PCI) sub-scale score change in Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, administered at baseline, 3-, 6-, 9-, 12-, and 15-month follow-up session. Per-protocol ICI and control arms were matched with propensity scores that incorporated baseline variables to compare both NBT and PCI assessment results. Patients participating in PCI assessments were analysed in intention-to-treat analysis. Kaplan-Meier survival curves with log-rank tests were adopted to analyse incidence of perceived cognitive decline events (PCDE)., Findings: Between March 12, 2020, and March 28, 2021, 908 participants were enrolled. Compared to control, 3 of 4 subtest of NBT scores in ICI arm showed significant cognitive decline in 6- and 12-month sessions, in which Trail Making Test score change (13.56 ± 11.73) reached threshold of cognitive deficit diagnosis in the 12-month session. In 1:1 matched 292 pairs from 908 patients, PCI score changes in ICI arms were -4.26 ± 8.54 (3rd month), -4.72 ± 11.83 (6th month), -6.16 ± 15.41 (9th month), -6.07 ± 15.71 (12th month), and -7.96 ± 13.97 (15th month). The scores were significantly lower than control arm in 3-, 6-, and 12-session follow-up. The result was validated after adjusting quality of life scores and in intention-to-treat analysis. Mean PCI change exceeded 1/2 SD of baseline PCI score (5.81) in 9-, 12-, and 15-month sessions in ICI arm, but not in control arm. PCDE incidence/prevalence was significantly higher in ICI arm (incidence 26.4% vs. 5.1%, and prevalence 16.2% vs. 1.7%). Immune-related adverse events related to incidence of PCDE after adjusting for baseline variables., Interpretation: ICI monotherapy seemed to relate to higher cognitive decline represented by score changes and incidence/prevalence rates. The decline deteriorated as treatment progressed, and immune-related adverse events seemed to be associated with higher cognitive adverse events incidence in the ICI treatment., Funding: The Fellowship of China Postdoctoral Science Foundation and National Natural Science Foundation of China Youth Science Fund Project., Competing Interests: We declare no competing interests., (© 2023 The Author(s).)

Purpose: This study investigated the relationship between serum lipid levels and clinical outcomes in acute myeloid leukemia (AML) by establishing a predictive risk classification model., Method: A total of 214 AML patients who were pathologically diagnosed and treated with standard induction chemotherapy at Sun Yat-Sen University Cancer Center were included. The patients were randomly divided into the training (n = 107) and validation (n=107) cohorts. Univariate and multivariate Cox analyses were used to assess the value of triglyceride (TG), Apolipoprotein B (Apo B), Apo Apolipoprotein A-I (Apo A-I), cholesterol (CHO), and high-density lipoprotein (HDL) as prognostic factors for AML., Results: After a series of data analyses, a five-factor model was established to divide the patients into high- and low-risk groups. Kaplan-Meier survival analysis showed that the high-risk group had a poor prognosis ( P <0.05). The area under the curve of the novel model for five-year OS was 0.737. A nomogram was constructed to integrate the model with age and the 2017 ELN cytogenetic classification, with the merged model showing improved accuracy with an area under the curve of 0.987 for five-year OS., Conclusion: A novel model was constructed using a combination of the serum lipid profile and clinical characteristics of AML patients to enhance the predictive accuracy of clinical outcomes. The nomogram used the lipid profile which is routinely tested in clinical blood biochemistry and showed both specific prognostic and therapeutic potential., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bai, Wang, Shao, Fu, Lu, Wang, Lu and Wang.)

Objectives: The current study aims to survey the willingness of parents to vaccinate their children, who are childhood acute lymphoblastic leukemia survivors (CALLS), and identify factors associated with vaccine acceptance. Methods: Parents of CALLS on/off treatment, with the general condition of being amendable to vaccination, were recruited for interviews with attending oncologists about COVID-19 vaccination acceptance from July to November 2021 in China. After controlling for socioeconomic factors, the Association of Oncologists’ recommendations and parent−oncologist alliance with acceptance status were investigated. For validation, propensity score-matched (PSM) analysis was used. Results: A total of 424 families were included in the study, with CALLS mean remission age of 5.99 ± 3.40 years. Among them, 91 (21.4%) agreed, 168 (39.6%) hesitated, and 165 (38.9%) parents disagreed with the vaccination. The most common reason that kept parents from vaccinating their children was lack of recommendations from professional personnel (84/165, 50.9%), and massive amounts of internet information (78/175, 44.6%) was the main nonhealthcare resource against vaccination. Logistic regression analysis showed that only the recommendation from the oncologist was associated with parents’ vaccine acceptance (OR = 3.17, 95% CI = 1.93−5.20), as demonstrated by PSM comparison (42 in recommendation group vs. 18 in nonrecommendation group among 114 pairs, p < 0.001). An exploratory analysis revealed that parents with a better patient−oncologist alliance had a significantly higher level of acceptance (65.6% in alliance group vs. 15.6% in nonalliance group among 32 pairs, p < 0.001). Conclusions: Due to a lack of professional recommendation resources and the potential for serious consequences, parents were generally reluctant to vaccinate their CALLS. The recommendation of oncologists, which was influenced by the parent−oncologist alliance, significantly increased acceptance. This study emphasizes the critical role of oncologists in vaccinating cancer survivors and can be used to promote COVID-19 vaccines among vulnerable populations.

Background: Ferroptosis is an iron-dependent mode of cell death that could be induced by erastin and exert antitumor effects. However, the clinical and biological roles of ferroptosis-related gene (FRG) signature and the therapeutic value of erastin in multiple myeloma (MM) remained unknown., Methods: Clinical and gene expression data of MM subjects were extracted from the Gene Expression Omnibus (GEO) public database. Univariable cox analysis was applied to determine FRGs related to survival and the least absolute shrinkage and selection operator (LASSO) regression analysis was used to develop a prognostic model. Prediction accuracy of the model was estimated by receiver operating characteristic (ROC) curves. Functional pathway enrichments and infiltrating immune status were also analyzed. We conducted in vitro experiments to investigate the combination therapy of erastin and doxorubicin., Results: 17 FRGs were strongly associated with patient survival and 11 genes were identified to construct the prognostic model. ROC curves indicated great predictive sensitivity and specificity of the model in all cohorts. Patients were divided into low- and high-risk groups by median risk score in each cohort and the survival of the low-risk group was significantly superior than that of the high-risk group. We also observed a close relevance between functional pathways and immune infiltration with risk scores. Moreover, we combined erastin and doxorubicin in our in vitro experiments and found synergetic antitumor effects of the two agents, and the underlying mechanism is the overgeneration of intracellular Reactive Oxygen Species (ROS)., Conclusions: We demonstrated the important value of ferroptosis in patient prognosis and as a potential antitumor target for MM., (© 2022. The Author(s).)

Background: Natural killer/T-cell lymphoma (NKTL) is difficult to treat. Circular RNAs (circ RNAs) have been implicated in tumorigenesis. However, the function of circKIF4A in NKTL has not been investigated. Methods: QPCR analysis was used to compare circKIF4A levels in NKTL cell lines versus normal cell lines. Kaplan-Meier survival analysis was used to assess the effect of circKIF4A on the prognosis of NKTL. The correlation between clinicopathological features and circKIF4A expression was examined using cox regression analysis. Luciferase reporter, RNA immunoprecipitation and immunohistochemistry assays were also used to investigate the mechanisms of circKIF4A in NKTL. Results: Our analyses revealed that circKIF4A is significantly upregulated in NKTL cell lines and that its upregulation correlates with the poor prognosis of NKTL. The silencing of circKIF4A significantly suppressed glucose uptake and lactate production in NKTL cells. Moreover, we showed that circKIF4A, PDK1, and BCL11A bind miR-1231 and that circKIF4A regulates PDK1 and BCL11A expressions by sponging miR-1231. Conclusions: During NKTL progression, circKIF4A regulated PDK1 and BCL11A levels by sponging miR-1231. Our data indicated that circKIF4A is oncogenic in NKTL and that it is a predictor of poor prognosis of NKTL.

Introduction: The response is poorly understood to the third dose in patients with cancer who failed the standard dose of inactivated SARS-CoV-2 vaccines (CoronaVac). We aim to assess the immune response to the third dose and identify whether vitamin D deficiency is associated with serial serologic failure in patients with cancer., Methods: Solid cancer patients (SCP-N) and healthy controls (HCs) who were seronegative after the standard-dose vaccines in our previous study were prospectively recruited, from October 2021 to February 2022, to receive the third dose vaccines and anti-SARS-CoV-2S antibodies were measured. SCP-N who failed the third dose (serial seronegative group, SSG) were matched by propensity scores with the historical standard-dose positive cancer patient group (robust response group, RRG). An exploratory analysis was carried out to validate the role of vitamin D on the serology response., Results: The multi-center study recruited 97 SCP-N with 279 positive controls as RRG and 82 negative controls as HC group. The seroconversion rate after third-dose vaccination was higher in SCP-N than in HC (70.6% vs. 29.4%, p < 0.01). The matched comparison showed that patients in SSG had a significantly lower level of vitamin D and consumption rate than RRG or RRG-B (RRG with third-dose positive) (all p < 0.01). None had serious (over grade II) adverse events after the third dose., Conclusion: Solid cancer patients with second-dose vaccine failure may have a relatively poor humoral response to the third dose of COVID-19 vaccines as compared with the seronegative HC group. The consecutively poor humoral response could be associated with poor vitamin D levels and intake. Vitamin D status and cancer-related immune compromise may jointly affect the humoral response following booster vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ma, Zhu, Zhong, Wang, Cao, Bai, Wang, Zhang and Wang.)

Purpose: The interaction between tumor cells and tumor microenvironment (TME) has an important impact on progression and prognosis of multiple myeloma (MM), and has been proven to be promising therapeutic targets. This study intended to explore the relationship between TME and prognosis and identify valuable biomarkers of MM., Methods: The transcriptomic and clinical information of MM retrieved from the Gene Expression Omnibus (GEO) were used to establish the model. The curve of Kaplan-Meier survival and the time-dependent receiver operating characteristic (ROC) were used to appraise the predictive ability. A nomogram was established for clinical application. Furthermore, the CIBERSORT algorithm was used to investigate the relation between IRGPI with the infiltration of immune cells. We also used histology, as well as in vitro and in vivo experiments to validate these findings., Results: The results demonstrated an immune-related gene-based prognostic index (IRGPI) combined with clinical information. Patients were separated into high- and low-risk groups based on risk score, which had significantly difference in survival status and immune infiltrations. Furthermore, we identified CXCL11 as a key factor, which positively promotes the progression of MM and correlate with macrophage M2-like polarization and tumor immune cells infiltration., Conclusion: Our findings suggest the IRGPI significantly demonstrate the differential prognosis and prediction of immune cells infiltration. It provides some insights into the complex interaction between myeloma tumor cells and the TME, as well as in the development of a novel biomarker target for anti-MM therapy., (© 2022. The Author(s).)

Purpose: Pyroptosis is an inflammation-based programmed cell death that holds great potential as a novel cancer therapeutic target in patients with multiple myeloma (MM). However, thus far, the function of pyroptosis-related genes (PRGs) in MM and their prognostic relevance remains undetermined., Methods: The model was established by the LASSO analysis, based on the Gene Expression Omnibus (GEO) dabatase, and its efficacy was verified using two external datasets. The model's predictive ability was assessed by the Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) curves. Finally, a nomogram was established for clinical application. We also confirmed the validity of our model using specimens and in vitro experiments., Results: We established an 11-PRG signature profile, and verified its efficacy using two validation cohorts (VCs). In both cohorts, patients were separated into two subpopulations, according to their median risk scores (RS). Our analysis revealed that high-risk (HR) patients experienced considerably lower overall survival (OS), compared to the low-risk (LR) patients. Using functional enrichment and immune infiltration analyses, we demonstrated that the immunologic status was strongly related to RS. Furthermore, using a pyroptosis inhibitor Q-VD-OPh, we revealed that MM cell proliferation and progression was drastically suppressed and the doxorubicin (DOX)-induced apoptosis was reversed., Conclusion: Based on our analysis, pyroptosis not only serves as a measure of MM treatment efficiency and patient prognosis, but is also a possible target for anti-MM therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Shao, Lu, Bai, Fu, Lai and Lu.)