Mediterranean Journal of Hematology and Infectious Diseases最新文献

The treatment outcomes of patients with chronic lymphocytic leukemia (CLL) have considerably improved with the introduction of targeted therapies based on Bruton kinase inhibitors (BTKIs), venetoclax, and anti-CD20 monoclonal antibodies. However, despite these consistent improvements, patients who become resistant to these agents have poor outcomes and need new and more efficacious therapeutic strategies. Among these new treatments, a potentially curative approach consists of the use of chimeric antigen receptor T (CAR-T) cell therapy, which achieved remarkable success in various B-cell malignancies, including B-cell Non-Hodgkin Lymphomas (NHLs) and B-acute lymphoblastic Leukemia (ALL). However, although CAR-T cells were initially used for the treatment of CLL, their efficacy in CLL patients was lower than in other B-cell malignancies. This review analyses possible mechanisms of these failures, highlighting some recent developments that could offer the perspective of the incorporation of CAR-T cells in treatment protocols for relapsed/refractory CLL patients.

The study of monoclonal serum proteins has led to the generation of two major theories: one proposing that individuals who had monoclonal proteins without any symptoms or evidence of end-organ damage have a benign condition, the other one suggesting that some individuals with asymptomatic monoclonal proteins may progress to multiple myeloma and thus are affected by a monoclonal gammopathy of undetermined significance (MGUS). Longitudinal studies of subjects with MGUS have supported the second theory. Subsequent studies have characterized and defined the existence of another precursor of multiple myeloma, smoldering multiple myeloma (SMM), intermediate between MGUS and multiple myeloma. Primary molecular events, chromosome translocations, and chromosome number alterations resulting in hyperploidy, required for multiple myeloma development, are already observed in myeloma precursors. MGUS and SMM are heterogeneous conditions with the presence of tumors with distinct pathogenic phenotypes and clinical outcomes. The identification of MGUS and SMM patients with a molecularly defined high risk of progression to MM offers the unique opportunity of early intervention with a therapeutic approach on a low tumor burden.

Background and objectives: Chronic active Epstein-Barr virus disease (CAEBV) is a proliferative disease of EBV⁺ T or natural killer (NK) cells with an unclear pathogenesis. This study aimed to examine the frequency and exhaustion levels of lymphocyte subsets in patients with CAEBV to further investigate the pathogenesis.

Methods: Using flow cytometry, we detected the frequency, expression levels of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1), and EBV infection status of peripheral T subsets and NK cells in patients with CAEBV and healthy individuals.

Results: 24 patients and 15 healthy individuals were enrolled in this study. Patients showed notably higher expression levels of PD-1 and PD-L1 in peripheral T subsets and NK cells compared to healthy individuals (P < 0.05). EBV⁺ lymphocytes exhibited significantly higher PD-L1 expression levels than EBV^- lymphocytes. Additionally, the frequency of effector memory T (Tem) cells was significantly increased in patients, and the PD-L1 expression level was positively correlated with the EBV load. Besides, helper T cell 2 (Th2) immune bias, also favoring EBV amplification, was found in patients, including increased Th2 cell frequency, enhanced response capacity, and elevated serum levels of associated cytokines. The distribution and PD-1 expression levels of peripheral T subsets returned to normal in patients who responded to PD-1 blockade therapy.

Conclusions: The up-regulation of the PD-1/PD-L1 pathway of peripheral T and NK cells and Th2 immune predominance jointly promoted EBV replication and the development of CAEBV. PD-1 blockade therapy reduced the PD-1 expression level of lymphocytes and helped normalize the distribution of the T subsets.

Epstein-Barr virus (EBV) is a prevalent virus that can be detected in the vast majority of the population. Most people are asymptomatic and remain chronically infected throughout their lifetimes. However, in some populations, EBV has been linked to a variety of B-cell lymphoproliferative disorders (LPDs), such as Burkitt lymphoma, classic Hodgkin lymphoma, and other LPDs. T-cell LPDs have been linked to EBV in part of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other uncommon histotypes. This article summarizes the current evidence for EBV-associated LPDs in light of the upcoming World Health Organization classification and the 2022 ICC classification.

Background: The nonvitamin K antagonist oral anticoagulants (NOACs) have become the mainstay anticoagulation therapy for patients requiring oral anticoagulants (OACs) in the Gulf Council Cooperation (GCC) countries. The frequency of NOAC-associated major bleeding is expected to increase in the Emergency Department (ED). Nonetheless, we still lack local guidelines and recommendations for bleeding management in the region. The present Delphi-based consensus aims to establish a standardized and evidence-based clinical care pathway for managing NOAC-associated major bleeding in the Kingdom of Saudi Arabia (KSA) and the United Arab Emirates (UAE).

Methods: We adopted a three-step modified Delphi method to develop evidence-based recommendations through two voting rounds and an advisory meeting between the two rounds. A panel of 11 experts from the KSA and UAE participated in the consensus development.

Results: Twenty-eight statements reached the consensus level. These statements addressed key aspects of managing major bleeding events associated with NOACs, including the increased use of NOAC in clinical practice, clinical care pathways, and treatment options.

Conclusion: The present Delphi consensus provides evidence-based recommendations and protocols for the management of NOAC-associated bleeding in the region. Patients with major DOAC-induced bleeding should be referred to a well-equipped ED with standardized management protocols. A multidisciplinary approach is recommended for establishing the association between NOAC use and major bleeding. Treating physicians should have prompt access to specific reversal agents to optimize patient outcomes. Real-world evidence and national guidelines are needed to aid all stakeholders involved in NOAC-induced bleeding management.

Background: Cytomegalovirus (CMV) infection remains the most common clinically significant infection after allogeneic hematopoietic stem cell transplantation (allo-HCT) and is associated with considerable morbidity and mortality.

Objectives: The present study was designed to describe and compare the incidence of untreated CMV reactivation (uCMVr), clinically significant infection (cs-CMVi) and disease (CMVd), as well as CMV-related hospitalization and outcome of allo-HCT patients, either treated with letermovir (LET) primary prophylaxis or managed with preemptive therapy (PET).

Methods: This is a prospective observational cohort study of adult CMV seropositive allo-HCT patients who either received primary prophylaxis with LET within the first 100 days after HCT or were managed with PET.

Results: The study population comprised 105 patients (28 in the LET group and 77 in the PET group). Compared to the PET group, patients in the LET group received more allo-HCT from alternative donors (54.5% vs. 82.14%, P=0.012). More than half of the patients in both groups were classified as high risk for CMVd. In the LET vs. PET group, cs-CMVi and CMVd developed respectively in 0 vs. 50 (64.94%), P=<0.0001, and 0 vs. 6 (7.79%), P=0.18. In the LET group, uCMVr occurred in 5 (17.8%) and were all considered blips. Hospital admissions related to cs-CMVi or CMVd in the PET group vs. LET group were 47 (61.04%) vs. 0, respectively, P=<0.0001. No differences were observed in 100-day mortality.

Conclusions: LET primary prophylaxis proved effective in preventing cs-CMVi and CMVd and reducing hospitalizations in allo-HCT adults. Blips can occur during prophylaxis and do not require LET discontinuation.

The aim of this study was to investigate the prognostic factors of haploid hematopoietic stem cell transplantation in the treatment of X-linked lymphoproliferative syndrome. Seven children with X-linked lymphoproliferative syndrome diagnosed by XIAP gene analysis were enrolled. The conditioning regimens were tolerated in all seven patients, and the median time of neutrophil engraftment was 10 days (8-13 days), and that of platelet engraftment was 21 days (14-24 days). STR-PCR analysis on the peripheral blood cells showed complete donor origins. Four cases developed Grade I acute graft versus host disease (aGVHD), one developed Grade III aGVHD (intestinal tract), and two cases had limited chronic GVHD. Four cases had cytomegalovirus (CMV) reactivation, and two cases had Epstein-Barr virus (EBV) reactivation. One case was diagnosed as pneumocystosis, and thrombotic microangiopathy (TMA) occurred in three cases. During the follow-up period (median time of 42 months), one patient died of TMA and six patients survived. Statistical analysis showed that the status of disease remission and the positive result of virus in blood before transplantation were independent prognostic factors. Haplo-HSCT might be a curative option for children with refractory X-linked lymphoproliferative syndrome. Low-intensity conditioning regimens may reduce transplant-related mortality and improve overall survival.