Objective This study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic. Design Retrospective cohort study between 2018 and 2021. Setting The largest haematological centre in southern China. Results A total of 599 episodes of BSI occurring in 22 717 inpatients from January 2018 to December 2021 were analysed. The frequencies of the total, Gram-negative and Gram-positive BSI before and during the pandemic were 2.90% versus 2.35% (p=0.011), 2.49% versus 1.77% (p<0.001) and 0.27% versus 0.44% (p=0.027), respectively. The main isolates from Gram-negative or Gram-positive BSI and susceptibility profiles also changed. The 30-day mortality caused by BSI was lower during the pandemic (21.1% vs 14.3%, p=0.043). Multivariate analysis revealed that disease status, pulmonary infection and shock were independent predictors of 30-day mortality. Conclusion Our data showed that the incidence of total and Gram-negative organisms BSI decreased, but Gram-positive BSI incidence increased in patients with HMs during the pandemic along with the changes of main isolates and susceptibility profiles. Although the 30-day mortality due to BSI was lower during the pandemic, the new infection prevention strategy should be considered for any future pandemics.

The incorporation of CD38-targeted monoclonal antibodies into induction therapy has improved outcome in patients with newly diagnosed multiple myeloma (NDMM), yet the benefit across risk subgroups remains controversial. We conducted a systematic search of the Cochrane Library, PubMed, Embase, Scopus, and Web of Science databases to identify studies comparing induction regimens with and without anti-CD38 monoclonal antibodies (daratumumab or isatuximab) and assessed the efficacy and safety of anti-CD38–based induction regimens in NDMM. Primary outcomes were minimal residual disease (MRD)-negativity and progression-free survival (PFS). Eleven trials encompassing 5588 patients, including 915 with high-risk multiple myeloma (HRMM), were included. Anti-CD38–containing regimens significantly increased MRD-negativity in both transplant-eligible (TE; pooled odds ratio [OR], 2.32; 95% confidence interval [CI], 1.74-3.11) and transplant-ineligible (TIE; pooled OR, 3.26; 95% CI, 2.20-4.84) patients. Among TE patients, MRD-negativity improved in both HRMM (pooled OR, 2.01; 95% CI, 1.41-2.88) and standard-risk MM (pooled OR, 2.74; 95% CI, 1.99-3.84). Anti-CD38 therapy also significantly prolonged PFS in TE (pooled hazard ratio [HR], 0.52; 95% CI, 0.38-0.69) and TIE NDMM (pooled HR, 0.55; 95% CI, 0.49-0.61), with an overall survival benefit observed in TIE patients. PFS improvement was consistent across cytogenetic risk and clinical subgroups. Grade 3 or 4 infections and hematologic toxicities occurred more frequently with anti-CD38 regimens. In summary, anti-CD38–based induction improves depth of response and PFS across NDMM populations, including high-risk disease, with increased but manageable toxicity.

Multiple myeloma (MM) remains an incurable malignancy characterized by the proliferation of malignant plasma cells and significant dysregulation within the bone marrow microenvironment. Plasmacytoid dendritic cells (pDCs) play a crucial role in the immune landscape of MM, often being co-opted by MM cells to support tumor progression. In this study, we identified all-trans retinoic acid (RA) as a potent modulator of pDC function through a high-throughput screening of 2,000 small-molecule drugs. RA significantly enhances pDCs’ capacity to secrete interferon (IFN)-α upon CpG or Resiquimod stimulation, reversing the MM-induced suppression of IFN-α secretion. Mechanistically, RA upregulates Toll-like receptor (TLR)7/9 expression in pDCs, amplifying TLR7/9 agonist-induced IFN-α production and enhancing retinoic acid-inducible gene Ⅰ (RIG-Ⅰ)-like signaling and IFN-stimulated gene expression. In vivo, RA combined with CpG or Resiquimod significantly improves the survival of MM-bearing mice, with even greater pro-survival benefits observed when RA, Resiquimod, and bortezomib are combined. These findings demonstrate that RA rejuvenates pDCs, leading to improved control of MM growth in preclinical models, offering novel insights into developing more effective MM therapies.

Observational studies have reported associations between multiple sclerosis (MS) and hematologic malignancies (HM), but findings remain inconsistent. We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association summary statistics for MS (n = 115,803) and HM (n = 218,792). Primary causal estimates were obtained with the inverse-variance-weighted (IVW) estimator, complemented by prespecified sensitivity analyses for heterogeneity and pleiotropy. Genetically proxied liability to MS was associated with higher odds of leukemia (unspecified subtype) (odds ratio [OR] 1.311, 95% confidence interval [CI] 1.002-1.716, P = 0.048) and Hodgkin lymphoma (HL) (OR 1.224, 95% CI 1.052-1.425, P = 0.009), with no evidence for other leukemia, lymphoma, or plasma-cell neoplasm subtypes (all P > 0.05). Tests indicated no substantial heterogeneity or directional pleiotropy for the leukemia (unspecified subtype) or HL analyses. These results provide genetic evidence consistent with an elevated risk of select HM subtypes among individuals with higher genetic liability to MS; however, the signals should be interpreted cautiously and validated in larger, multi-ancestry datasets and with additional causal frameworks.