The significance of serum beta-2 microglobulin (sβ₂m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sβ₂m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8–3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sβ₂m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sβ₂m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff (“normal versus high”). In multivariate analysis, sβ₂m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sβ₂m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sβ₂m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sβ₂m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a “normal versus high” cutoff set at 2.4 mg/L.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6–10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is currently focused on the potential role of genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the transforming growth factor-beta (TGF-β) pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future, as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield reliable results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. This review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare, aggressive B-cell lymphoma, sharing common features with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). PMLBCL is usually cured with single-hit immunochemotherapy in the first-line setting. Relapses tend to be aggressive and may be unresponsive to conventional chemotherapy. Autologous stem cell transplant (ASCT) remains a viable option for chemosensitive patients; nevertheless, targeted therapies appear to be highly promising. Checkpoint inhibitors (CPIs) have already transformed the course of relapse/refractory disease, while CD-19-directed Chimeric Antigen Receptor (CAR) T-cell therapy may produce remarkably favorable outcomes. The exact position of CAR T-cells and CPIs in the treatment algorithm, along with the role of radiotherapy and ASCT, remains to be precisely determined. In the current review, we aim to present the recent research on targeted agents in PMLBCL and define their sequencing within the treatment algorithm, mainly in the relapse/refractory setting.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Background: Haemoglobinopathies are the most common monogenic disorders both in Greece and worldwide. The most effective strategies against them are carrier detection and prenatal testing following genetic risk assessment consultation for couples on the likelihood of their offspring being affected. Case Presentation: A novel alpha globin chain variant, named Hb Thessaloniki, was detected in Northern Greece. The underlying point variation HBA1:c.260T>C (ref. seq. NM_000558.5) was detected in the HBA1 gene, in heterozygosity, during a routinely performed population screening for haemoglobinopathies. The amino-acid residue Leu86 was replaced by a structure disrupting Pro residue, resulting in a hyperunstable product as shown by the isopropanol test and predicted by the Dynamut2 and Alphafold3 algorithms. The haematological phenotype, due to which genetic analysis was performed, presented with mild microcytosis and hypochromia and was also indicative of the presence of an unstable haemoglobin produced in small quantities (variant encoded by HBA1). Since the proband’s partner presented with a normal haematological phenotype, there is no risk of the couple giving birth to an affected offspring. Expanded analysis of the proband’s relatives identified biallelic variants (α^Parmaα/αα^{Τhessaloniki}) in the proband’s mother, who presented with no apparent clinical findings, expect for slightly reduced haematological indices. Conclusions: The novel Hb Thessaloniki identified, although theoretically hyperunstable, seems to have minor effects on erythrocyte function, as indicated by haematological findings on the proband and his close relatives. Future identification of co-inheritance with HBA pathogenic point variations or deletions may provide further information regarding genetic counselling. In parallel, the usage of structure–function relation-calculating algorithms may enhance our prediction capability for novel variants.