Mediterranean Journal of Hematology and Infectious Diseases最新文献

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.

Despite the introduction of several therapies in recent years, multiple myeloma (MM) remains a hematologic malignancy difficult to treat due to its extreme inter- and intra-patient heterogeneity. However, at the 2024 major international conferences, very significant data have emerged on new approaches that can improve outcomes even in high-risk or very advanced diseases. Up-front quadruplet combinations, including anti-CD38 monoclonal antibodies, proved to be the best therapy in terms of depth of response and long-term efficacy in both transplant-eligible and not-eligible patients with MRD assessment that could play a key role in determining the duration of therapy, avoiding unnecessary overtreatment. However, quadruplets also fail to overcome the negative prognostic value of high-risk cytogenetics or circulating tumour cells; therefore, in patients with these features, alternative approaches will have to be evaluated. Moreover, considering that not all patients, particularly older and frail ones, will be able to undergo such therapies, it will be necessary to refine the ability to identify the most appropriate therapy for each patient. Bispecific antibodies and CAR-T cells represent the new frontier in the treatment of advanced MM. However, they have shown even more efficacy with less toxicity in early relapses and functional high-risk patients. In the upfront setting, the results obtained with the inclusion of novel immunotherapies are extremely promising. In relapsed/refractory MM patients, agents such as belantamab mafodotin and CELMoDs, in combination with proteasome inhibitors or immunomodulatory agents, may represent another valid option.

Multiple myeloma is a malignant haematological neoplasm characterised by the proliferation of plasma cells in the bone marrow. Each year, over 35,000 new cases are diagnosed in the United States, and nearly 13,000 patients die from the disease.1 The main cause of morbidity is bone disease, characterised by osteolytic lesions, which, unlike other malignancies that metastasise to bone, are not followed by new bone formation.2 Other major clinical manifestations include anaemia, hypercalcemia, renal failure, and an increased risk of infections. Approximately 1-2% of patients present with extramedullary disease (EMD) at the time of diagnosis, while 8% develop EMD later in the course of the disease.3 Although multiple myeloma remains incurable, its treatment continues to evolve rapidly. Approved therapies include immunomodulatory agents (IMiDs, such as thalidomide, lenalidomide, and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), and monoclonal antibodies (mAb) targeting CD38 (especially daratumumab and isatuximab) and SLAMF7. New therapeutic avenues include bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) therapy.4-5 The latest ESMO (European Society for Medical Oncology)6 and NCCN (National Comprehensive Cancer Network) guidelines7 have set the standard of care for patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation, particularly those in good general condition and < 70 years old. This approach is divided into four phases: induction therapy, hematopoietic stem cell collection, and autologous transplant, consolidation, and maintenance. The most significant differences between the guidelines occur during the induction phase, influenced by regulatory approvals in the United States and Europe. This article will focus on the changing landscape of therapies for newly diagnosed multiple myeloma (NDMM) in transplant-eligible.

Background: New targeted therapies have revolutionized the treatment landscape in CLL. Biological features, patient characteristics and preferences and the safety profile of each treatment option should be taken into consideration for making the optimal treatment choice. This consensus practice statement on CLL treatment was developed by a group of Greek experts in CLL based on the available evidence for both first-line treatment and the relapsed/refractory setting.