Mediterranean Journal of Hematology and Infectious Diseases最新文献

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.

Background: Discrimination between clonal and reactive cell proliferation is critical for the correct management of T-cell lymphocytosis. Multiparametric flow cytometry (MFC) represents a valuable tool, particularly because it allows the evaluation of the T-cell receptor (TCR) Vβ repertoire to pinpoint eventual clonality in T-cell lymphocytosis. A restricted expansion of a single out of the 24 evaluable families or a "clonogram-off" pattern is highly suggestive of the presence of a clonal T-cell population. However, data available on the concordance between MFC TCR-Vβ repertoire and molecular analysis of TCR gene rearrangements, which is regarded as the gold standard for assessing T-cell clonality, are limited.

Objective and methods: We performed a retrospective monocentric study involving 307 patients referred to our center for lymphocytosis between 2003 and 2024. The aim of our study was to investigate the diagnostic accuracy of MFC TCR-Vβ repertoire analysis and compare its performance with molecular analysis of TCR gene rearrangements for the identification of T-cell clonality.

Results: In clonally restricted cases, MFC TCR-Vβ repertoire analysis demonstrated a restricted expansion of a single Vβ family in 67.5% of cases, while a "clonogram-off" pattern inferred clonality in the remaining 32.5%. For 215 (70%) patients, both MFC TCR-Vβ repertoire analysis and molecular analysis of TCR gene rearrangements were available, showing an absolute concordance (215 out of 215 cases, 100%) between the two methods.

Conclusion: MFC TCR-Vβ repertoire analysis is a rapid, cheap, sensitive, and reliable tool to identify clonal T-cell lymphocytosis. It represents an absolutely valid first-line diagnostic approach, and it should be included in the routine laboratory work-up performed on MFC analysis for peripheral lymphocytosis.