Mediterranean Journal of Hematology and Infectious Diseases最新文献

Treatment outcomes for patients with multiple myeloma have improved in recent decades thanks to new insights into the biology of the disease and the introduction of new drugs and therapeutic approaches. More than half of patients with multiple myeloma are not eligible for transplantation, and for years, their treatment has been difficult due to the heterogeneity of this patient group and the lack of treatment options. Recently, attention has focused on the concept of frailty and its quantification in order to adapt the schedule and dosage of treatment to the state of fitness. Modulation of therapy for frailty can reduce side effects and toxicity-related death and define the various successes of therapy. The role of frailty and the development of new tools may provide a way forward to customize the treatment of different patients with multiple myeloma who are not eligible for transplantation. The use of the new association, particularly based on monoclonal antibodies against CD38, showed profound and durable results in terms of progression-free survival and overall survival. Today, these combinations, especially daratumumab-lenalidomide and dexamethasone, represent the "gold standard" of treatment for these patients. The latest quadruplet therapies and cell-directed therapies, including bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) treatment, appear to be very effective and achieve a high rate of negative minimal residual disease. These latter approaches could redefine the population over the age of 65 that is now considered transplant-eligible.

The diagnosis and treatment of Waldenstrom macroglobulinemia (WM) are the subjects of this two-part review, which aims to provide current and thorough knowledge of these topics. The first portion of the study, previously published, investigated the epidemiology, etiology, clinicopathological aspects, differential diagnosis, prognostic factors, and impact on WM-specific groups. Specifically, this second section examines both the standard consolidated method and the new therapeutic strategy to handle the complex topic of the treatment of WM.

Key points: WM has no cure, but therapies can improve survival. Treatment for WM/LPL patients should be initiated when they exhibit symptoms, and the IgM level should not determine WM treatment.Current guidelines suggest various initial personalized therapy treatments, typically chemoimmunotherapy (CIT) or BTK inhibitors (BTKi).Patients with WM can be put into three groups based on their MYD88 and CXCR4 mutational status: those with MYD88 mutations but no CXCR4 mutations (MYD88MUT/CXCR4WT), those with both MYD88 and CXCR4 mutations (MYD88MUT/CXCR4MUT) and those who do not have both MYD88 and CXCR4 mutations (MYD88WT/CXCR4WT).The objective of treatment is to alleviate symptoms and mitigate the risk of organ impairment.The timing of response evaluations, including BM, should be established on a case-by-case basis, informed by clinical and laboratory assessments.Patients with relapsed/refractory WM following chemotherapy and covalent Bruton tyrosine kinase inhibitors may choose non-covalent Bruton tyrosine kinase inhibitors, novel anti-CD20 monoclonal antibodies, BCL-2 inhibitors, or more intensive chemotherapy regimens.Patients who are younger and healthier and have not responded to both CIT and BTKi may be good candidates for an autologous stem cell transplant (ASCT).Second-generation anti-CD19 CAR T cells exhibit anti-WM activity in both in vitro and in vivo settings.From 2.4% to 11% of patients with WM undergo histological transformation, predominantly to diffuse large B-cell lymphoma (DLBCL). The median duration between diagnosis and transformation is 4.6 years.WM patients have a higher risk of secondary cancers.HSV and HZV prophylaxis may be beneficial for patients needing extensive treatment. Screening for Hepatitis B is necessary. Pneumocystis jiroveci prophylaxis is highly recommended. SARS-CoV- 2 and seasonal flu vaccines should be available to all WM patients.

Background: Platelets are the main components supporting coagulation and hemostasis. Nevertheless, no sufficient research has been done on how variations in platelet counts during hospital stays affect aplastic anemia (AA) patients' prognoses.

Objective: This study proposes to evaluate the association between alterations in platelet levels and illness risk in patients with AA using group-based trajectory modeling (GBTM).

Methods: GBTM was used to group AA patients based on changes in platelet levels. Cox regression models were used to evaluate the relationship between platelet levels and patients' 30-day survival status. Kaplan-Meier (K-M) survival curve analysis was used to assess the impact of platelet transfusion on survival among different trajectory groups of patients.

Results: Three trajectory patterns were recognized by GBTM: Class 1, Class 2, and Class 3. Even after controlling for confounding variables, the Cox risk estimates showed that AA patients had a higher chance of surviving in Class 1 (OR>1, P<0.05). Class 2 patients had the greatest survival, according to K-M (Log-rank P<0.001). According to landmark research, Class 1 patients' survival was not improved by platelet transfusion.

Conclusion: Patients with AA who had increasing platelet trajectories during their hospital stay had a higher 30-day survival rate; hence, patients with low platelet counts might not be good candidates for platelet transfusion treatment.

Leukemia Cutis (LC) in acute myeloid leukemia (AML) is typically managed within the context of systemic AML therapy, namely intensive chemotherapy (IC). In frail patients, though, viable options are hypomethylating agents (HMAs) associated with Venetoclax (VEN), but data on the efficacy of this approach in this specific setting is scarce. Here, we report our experience and provide a short review of the previous cases of LC treated with HMAs plus VEN to underline the efficacy of such treatment in LC patients who are unsuitable for IC.

Multiple myeloma is a disease related to the proliferation of malignant plasma cells; in most patients, the disease is confined to the level of bone marrow. However, in a minority of patients, the malignant plasma cells are also localized outside the bone marrow, either at the level of peripheral blood (plasma cell leukemia) or at the level of soft tissues (extramedullary multiple myeloma). These two rare forms of aggressive MM (ultrahigh-risk (uHR) MM as MM leading to death within 24-36 months) are both associated with some molecular features and with a limited response to current treatments.

Multiple myeloma (MM) is a heterogeneous disease, with MM patients experiencing different clinical outcomes depending on the disease's biological features. Novel insights into the molecular mechanisms of MM have led to the introduction of sophisticated drugs, which dramatically improved patient treatment and survival. To date, young patients with newly diagnosed MM could experience a median overall survival (OS) of 10 years. Nevertheless, a small proportion of patients still undergoes early disease progression and death. Indeed, cases defined as ultra-high-risk MM (uHRMM) and high-risk MM (HRMM) are destined for a worse outcome, with an OS of 2-3 and 3-5 years, respectively. In this regard, current risk stratification systems failed to identify this subset of patients better. The application of existing risk models has led to the identification of extremely heterogeneous categories of patients, and they have not taken into account biological and clinical differences. The concept of HRMM was initially formalised in 2015. Since then, a great effort has been made to identify those parameters whose presence pone MM patients at higher risk of developing an early relapse. The simultaneous presence of 2 or more unfavourable cytogenetic abnormalities, the identification of an extramedullary disease or the detection of circulating plasma cells, as well as high-risk gene expression profiling (GEP) signature, have shown to be well related to a worse outcome and are going to be incorporated into new prognostic systems. The introduction of the Individualised Risk Model for Multiple Myeloma (IRMMa) marks a significant advancement in the management of HRMM by integrating genomic and clinical data to tailor treatment strategies. This model demonstrates improved prognostic accuracy compared to traditional staging systems and emphasises the importance of personalised treatment approaches. The implementation of these advanced tools is essential for enhancing precision medicine in MM and improving outcomes for patients in high-risk categories.

Background: Current guidelines for screening glucose dysregulation (GD) in patients with transfusion-dependent thalassemia (TDT) recommend an annual 2-hour oral glucose tolerance test (OGTT) starting at the age of 10 years.

Objective: Assessment of adherence to OGTT screening in patients with TDT.

Methods: A questionnaire was distributed to 18 Thalassemia Centers in 10 different countries, targeting factors influencing adherence to annual OGTT screening in specialized multidisciplinary pediatric and adult TDT units and identifying strategies to improve adherence to OGTT in TDT patients.

Results: The mean reported percentage of all types of GD across 16 of the 18 centers at the last OGTT assessment was 32.0%, while the mean percentage for thalassemia-related diabetes mellitus (Th-RDM) was 12.2 ± 9.7% (range: 0%-41%; median: 13.2 %) in all participating centers. Notably, a high percentage of suboptimal or poor adherence to annual OGTT screening (mean 41.3%; range 10-90%) was reported by 17/18 centers. Poor adherence to annual OGTT among eligible patients was multifactorial and related to both patients and the healthcare system barriers. The most commonly suggested actions by hematologists and endocrinologists for improving the adherence to OGTT were flexibility in timing, easy approach to test location, improved collaboration among team members, and persistent reminding.

Conclusions: Young adult patients with TDT are at high risk for developing GD and Th-RDM. Thus, annual screening with a 2-hour OGTT is recommended. Nevertheless, several patient barriers are associated with low adherence to annual OGTT. It is desirable to develop intensive initiatives to improve the screening rate for GD, while studies are warranted to update the current guidelines in TDT patients with low-risk factors for GD and for countries with low-resource settings.

Background: Previous observational studies have suggested a potential causal relationship between Helicobacter pylori (H. pylori) infection and immune thrombocytopenia (ITP). However, the evidence for causal inference remains contentious, and the underlying mechanisms require further investigation. To delve deeper into the relationship between H. pylori and ITP, we conducted a Mendelian randomization (MR) analysis.

Method: In this study, we used two-sample Mendelian Randomization (MR) to assess the causality of seven different specific protein antibodies targeting H. pylori on ITP. 76 single nucleotide polymorphisms (SNPs) related to H. pylori antibody levels were obtained from the European Bioinformatics Institute (EBI). Summary data on ITP was obtained from the FinnGen database, and inverse variance weighted (IVW) analysis was identified as our main method. The reliability of the findings was ensured by performing many sensitivity analyses.

Result: Genetically predicted serum levels of H. pylori GroEL antibodies were positively associated with an increased risk of ITP (odds ratio [OR] = 1.802, 95% CI 1.106-2.936, P = 0.01799). No causal relationship was found between other H. pylori antibodies and ITP.

Conclusion: The outcomes derived from our two-sample Mendelian randomization analysis demonstrate a discernible link between the levels of H. pylori GroEL antibodies and an augmented susceptibility to ITP. However, it is imperative to expand the sample size further in order to corroborate the correlation between H. pylori infection and ITP.