Mediterranean Journal of Hematology and Infectious Diseases最新文献

Chimeric antigen receptor (CAR) T-cell therapy has improved the outcomes of patients with relapsed/refractory B-cell lymphomas, B-cell acute lymphoblastic leukemia, and multiple myeloma. However, CAR-T cell therapy is also associated with distinct toxicities that contribute to morbidity and mortality. A large number of studies now define the different toxicities associated with CAR-T cell therapy and have, in part, clarified their mechanisms. In particular, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two main acute toxicity events that occur after CAR-T cell infusion. Other CAR-T-related toxicities occur later after CAR-T cell infusion and include B-cell aplasia, hypogammaglobulinemia, infections, and cytopenias. Infections represent the main cause of non-relapse death observed in patients undergoing CAR-T cell therapy. Second primary malignancies are rare and are mainly represented by myeloid malignancies.

Background: To investigate the occurrence of Plasmodium vivax infections in Duffy-negative individuals, challenging the long-held belief that P. vivax requires the Duffy antigen receptor for chemokines to infect human erythrocytes.

Materials and methods: In the present study, 365 samples were screened using serological techniques, PCR-RFLP analysis, and DNA sequencing of the ACKR1 gene promoter region mutation to identify Duffy-negative individuals. P. vivax infection was detected using PCR targeting the 18S rRNA gene and microscopic examination of Giemsa-stained blood smears.

Results: Five individuals (1.36%) were confirmed Duffy-negative (Fy^(a-b-)). Surprisingly, 3 out of these 5 Duffy-negative subjects (60%) were infected with P. vivax, as confirmed by both microscopy and PCR. Various parasite stages were observed in infected Duffy-negative samples, with parasitaemia ranging from 0.01% to 0.5%.

Discussion: Our findings provide compelling evidence that P. vivax can infect Duffy-negative individuals, suggesting the existence of alternative invasion pathways or adaptations. This has profound implications for P. vivax biology, evolution, and global distribution. The burden of vivax malaria may be underestimated, particularly in regions with a high prevalence of Duffy negativity. This study highlights the need to reevaluate P. vivax epidemiology, diagnostic approaches, and control strategies, especially in areas previously considered at low risk. Further research is needed to elucidate the mechanisms enabling P. vivax invasion of Duffy-negative erythrocytes and to assess the clinical and epidemiological consequences of these infections.

T-cell redirecting therapies (TCR) marked a step forward in the treatment of relapsed/refractory multiple myeloma (RRMM). These agents, represented by chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsAbs), proved to ameliorate the prognosis of difficult-to-treat patients in pivotal clinical trials, leading to their introduction into clinical practice. Both strategies rely on recruiting patients' T-cells against specific tumor antigens, with B-cell maturation antigen (BCMA) and G-protein coupled receptor group C family 5 member D (GPRC5D) being the targets most extensively studied. Nevertheless, most of these regimens under the current label do not hesitate in a clear plateau of survival curves, thus raising the scenario of patients receiving more than one TCR agent in sequence. Also, they differ in their toxicity profiles and administration features. Consequently, the appropriate application of these agents mandates a careful selection of the right treatment for the right patient, with the ultimate intent of optimizing patient outcomes. In this respect, practical considerations regarding tumor- and patient-specific features are of high importance. Tailored clinical trials and analysis of real-word experiences are also crucial to produce evidence-based recommendations. Likewise, pre-clinical research is critical for the conceptualization of treatment algorithms potentially driven by immunological clues and knowledge of mechanisms of resistance. In this review we aim at providing practical guidance for defining the most appropriate treatment sequencing and determining the selection of patients for each treatment.

Background: Epstein-Barr virus (EBV), a human herpes virus, presents significant risks to hematopoietic stem cell transplant (HSCT) recipients due to immunosuppressive treatments. Two genotypes of EBV can infect humans: EBV1 and EBV2. These genotypes differ in their latent genes. One important latent protein is EBNA3, which plays a crucial role in immune evasion and pathogenesis of EBV.

Objectives: This study characterizes EBV genotypes among HSCT recipients in Jordan and examines the relationship between EBV positivity and demographic factors.

Methods: A retrospective observational study was conducted at the Jordanian Royal Medical Services Hospital (JRMS) from January to October 2024. Blood samples were collected from the virology department, and plasma was separated. EBV-DNA detection was performed using quantitative real-time PCR, while conventional PCR targeted EBNA3C genes for genotyping.

Results: Out of 93 EBV-positive HSCT recipients, 31 underwent genotyping analysis. The findings revealed a predominance of EBV2, detected in 26 samples (84%), while 5 samples (16%) exhibited mixed infections. Notably, EBV1 was not identified in any samples. A significant association was found between EBV positivity and male recipients, with a markedly higher prevalence in individuals under 18 years of age (P<0.0001).

Conclusion: EBV2 was the predominant genotype among HSCT recipients in Jordan, with coinfections of EBV1 and EBV2. Understanding the prevalent genotypes in transplant patients is crucial for managing EBV-related complications, ultimately improving patient outcomes. This study highlights the need for continuous monitoring and characterization of EBV genotypes in immunocompromised populations.

Current treatment strategies have led to unpredictable improvements in the management of multiple myeloma (MM) over time. However, resistance to therapy, particularly regarding lenalidomide refractoriness and, more recently, daratumumab and lenalidomide refractoriness, even in the first-line setting, has become an increasingly significant issue in recent years. This resistance complicates the identification of the optimal treatment algorithm for patients with relapsed/refractory MM, particularly at first relapse. In this review, we focus on current strategies for MM patients progressing on or after lenalidomide-based and daratumumab-lenalidomide-based regimens. The forthcoming availability of next-generation immunotherapies, along with a deeper understanding of resistance mechanisms, is highly anticipated. Meanwhile, based on promising results from recent studies, the approval of novel drugs to expand the current therapeutic armamentarium against MM is bringing us closer to the goal of making a potential cure for the disease much more achievable in the hopefully near future.