Hemato, Volume 6, Issue 1 (March 2025) – 7 articles

Thalassemia, once associated with limited survival, now sees extended life expectancy due to treatment advancements, but new complications such as pseudoxanthoma elasticum (PXE)-like syndrome are emerging. In fact, thalassemia patients develop PXE-like features more frequently than the general population. These features include skin lesions, ocular changes, and vascular issues like arterial calcifications, all linked to oxidative damage from iron overload. PXE-like syndrome in thalassemia mimics inherited PXE but is acquired. The underlying cause is thought to be oxidative stress due to iron overload, which induces free radicals and damages elastic tissues. Unlike inherited PXE, this form does not involve mutations in the ABCC6 gene, suggesting different pathogenic mechanisms, including abnormal fibroblast metabolism and oxidative processes. The vascular calcification seen in this syndrome often follows elastic fiber degeneration, with proteoglycans and glycoproteins acting as nucleation sites for mineralization. The condition can lead to severe cardiovascular and gastrointestinal complications. Studies have shown a significant incidence of PXE-like skin lesions in thalassemia patients, with some dying from cardiovascular complications. Research on ABCC6, a transporter protein involved in ectopic mineralization, has highlighted its role in various conditions, including PXE, beta-thalassemia, and generalized arterial calcification of infancy. ABCC6 mutations or reduced expression led to ectopic mineralization, affecting cardiovascular, ocular, and dermal tissues. The exact molecular mechanisms linking ABCC6 deficiency to ectopic mineralization remain unclear, though it is known to influence calcification-modulating proteins. This review focuses on the role of ABCC6 in the pathogenesis of calcifications, especially intracranial vascular calcifications in PXE and beta-thalassemia. Full article

Background: Chronic myeloid leukemia (CML) relates to the abnormal presence of the Philadelphia chromosome, which originates the production of the BCR-ABL1 fusion protein and therefore leads to neoplastic transformation and unregulated cell growth. The advent of tyrosine kinase inhibitors (TKIs) has resulted in tremendous improvements in CML scenarios; however, there are practical difficulties, especially considering the late stages of the disease. This review examines recently developed strategies that are intended to increase the efficiency of treatment by overcoming TKI resistance. Methods: We performed a literature review of such databases as PubMed, Scopus, Web of Science, and Embase for the last ten years. The following keywords were used in the studies: ‘CML’, ‘TKI resistance’, ‘novel therapies’, ‘immunotherapy’, ‘targeted agents’, and ‘combination therapies’. Only those studies were included that were clinical trials and preclinical across-the-board developmental programs that attempt to target the tumor at multiple levels and not just focus on basic first-line TKIs. Results: In CML patients who do not respond to TKIs, novel therapeutics encompass ponatinib, asciminib, CAR-T immunotherapy, and BCL-2 and mTOR inhibition in conjunction with TKI therapy. This addresses both BCR-ABL1-dependent and independent resistance mechanisms, increasing the chance of achieving deeper molecular response and reduced toxicity. Nonetheless, they exhibit diverse characteristics regarding efficacy, safety, cost, and quality of life effects. Discussion: Nonetheless, numerous challenges remain regarding the understanding of the mechanisms of resistance, the long-term efficacy of novel medicines, and the ideal combinations to attain optimal outcomes. Areas of future research include the search for other patterns of molecular resistance, tailoring specific treatments to patients, and incorporating AI to improve diagnosis and monitoring. Conclusion: The introduction of novel therapeutic techniques into clinical practice needs a collaborative approach and persistent dynamism to new findings from research. Our analysis indicates that the challenges posed by resistant CML disease are complex and require further improvements in therapeutic and clinical protocol development. Full article

Background/Aim: Omega-3 fatty acids, a key component of immunonutrition, have been used to modulate immune responses and improve clinical outcomes in various settings, including hematological patients undergoing hematopoietic stem cell transplantation (HSCT). This study aimed to summarize the effects of omega-3 supplementation on inflammation, long-term survival, and post-transplant complications, such as graft-versus-host disease (GVHD) and mucositis. Additionally, its impact on nutritional status and immune function was considered. Methods: A narrative review was conducted. The PubMed, Embase, and CINAHL databases were searched, along with sources of gray literature. From 2607 records, five studies met the inclusion criteria and were analyzed Results: The available literature suggests that omega-3 supplementation provides significant benefits, including reduced inflammation, lower C-reactive protein levels, and improved long-term survival. Furthermore, a reduction in GVHD and mucositis incidence was observed. The safety profile of omega-3 was favorable, with no serious adverse events reported. However, the evidence remains limited and heterogeneous, emphasizing the need for further well-designed trials to validate and expand upon these findings. Conclusions: Omega-3 fatty acids appear to be a promising intervention for improving clinical outcomes in HSCT patients. Additional research is essential to optimize treatment protocols and confirm its immunomodulatory role. Full article

Obesity is among the most prevalent risk factors in the severe forms of Coronavirus disease 2019 (COVID-19) infection. COVID-19 patients with obesity often face severe complications that might be associated with overexpression of adiponectin, inflammatory cytokines, and angiotensin-converting enzyme 2 (ACE2) receptors in visceral fat. The pre-existing subclinical inflammation associated with obesity can also lead to severe inflammatory responses. Elevation of proinflammatory cytokines considerably activates coagulation cascades, including the tissue factor (TF) pathway. The hypercoagulable state in COVID-19 is presented with severe pulmonary complications such as venous thromboembolism (VTE), disseminated intravascular coagulation (DIC), and disruption of vascular endothelial cells, which can lead to severe complications and death. The interaction between inflammatory response and coagulation mechanism in COVID-19 patients with obesity warrants a further understanding of prognosis and potential therapeutic approaches. This review discusses the crosstalk between inflammation and coagulopathy in obesity-related severe COVID-19 infection. Full article

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common diagnosed aggressive B-cell lymphoma, with poor outcomes in those who experience relapsed or refractory (R/R) disease. Landmark clinical trials have demonstrated the efficacy and safety of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for patients with R/R DLBCL, though further exploration of real-world outcomes (RWOs) and safety data is warranted. Methods: A retrospective chart review was performed to collect patient and disease characteristics from patients with R/R DLBCL receiving CAR T-cell therapy for third-line treatment or beyond at the John Theurer Cancer Center as the standard of care. Results: We report on 82 patients with R/R DLBCL that successfully completed an infusion of an anti-CD19 CAR T-cell product at our institution. Best overall and complete response rates were 74.4% (95% CI, 64.9 to 83.8) and 67.1% (95% CI, 56.9 to 77.2), respectively. From the time of CAR T-cell infusion, median PFS was 26.5 months (95% CI, 8.6 months could not be estimated) and OS was not reached. Subgroup analyses revealed no statistical differences in outcomes by use of bridging therapy, Karnofsky performance status, transformed DLBCL status, and the type of CAR T-cell product used for this study. CAR T-cell therapy was well tolerated, with 58 patients (70.7%) experiencing cytokine-release syndrome and 17 patients (20.7%) experiencing immune effector cell-associated neurotoxicity syndrome. Conclusions: These results of RWOs in third-line patients with R/R DLBCL receiving anti-CD19 CAR T-cell therapy are comparable or superior to prior clinical trials and studies of RWOs, validating the strong efficacy and manageable toxicities of CAR T-cell therapy. Full article

Background: Extracorporeal photopheresis (ECP) consists of the collection of a patient’s peripheral blood mononuclear cells (MNCs) that, after incubation with a photosensitive molecule, are exposed to ultraviolet-A (UVA) and then reinfused into the patient. There are two methods for performing the ECP procedure: the “in-line” methods and the “off-line” methods. In the “in-line” method, all the phases of ECP (leukapheresis, photoactivation, and reinfusion) are achieved sequentially in extracorporeal circulation using a single instrument and a single sterile disposable kit without disconnection from the patient’s blood circulation. In this paper, we report our real-life experience with a recently licensed in-line ECP system proposed by Fresenius-Kabi. Methods: The ECP procedures (n = 211) were performed using an Amicus cell separator and a Phelix UV irradiator with Amicus software 4.51 and Phelix software 1.0. A targeted 2000 mL of whole blood (WB) was processed, and 1.5 J/cm² of UVA light was delivered to the collected mononuclear cells (MNCs). Results: From May 2023 to April 2024, we performed 211 ECP procedures in 11 patients with graft-versus-host disease (GvHD). The processed blood volume was between 1992 and 2000 mL, and the blood flow speed during the procedures was highly variable (from 30 to 50 mL/min), so the total duration of the procedure was quite variable (from 92 to 118 min). The collection efficiency (CE2) for mononuclear cells was always satisfactory (from 55% to 73%), with a minimal presence of RBCs and PLTs. Conclusions: In our experience, the Amicus system-based ECP procedure is safe and well tolerated as we observed only one side effect. The duration of the procedure was always under two hours. The collection efficiency (CE2) for MNCs was satisfactory, with minimal platelet and RBC product contamination. Full article

Background/Objectives: Lutathera^® ([¹⁷⁷Lu]Lu-DOTA-TATE) is the first radiolabelled somatostatin (SST) analog approved for the treatment of patients with well-differentiated (G1 and G2) unresectable or metastatic gastro-entero-pancreatic neuro-endocrine-neoplasms (GEP-NENs). The bone marrow and kidneys are critical organs for RLT with [¹⁷⁷Lu]Lu-DOTA-TATE. Our purpose was to evaluate hematological and renal toxicity in 29 patients (18 males, 11 females) treated with Lutathera^®. Methods: According to standard protocols, four cycles of (¹⁷⁷Lu)Lu-DOTA-TATE were administered every eight/nine weeks. Patients received pre-medication with anti-emetic and anti-acid drugs and a slow amino acid infusion for renal protection. Blood count and serum creatinine data were collected at three time points: before the first cycle, after the second cycle, and at the end of treatment. Results: We found that almost all hematological parameters significantly decreased between the baseline and/or interim and post-therapy evaluation, although without a clinical impact. The presence of total tumor load or bone metastases had no influence on these findings, while male patients showed less hematological toxicity than females. Conversely, creatinine levels did not vary during treatment. Conclusions: Our study confirms that [¹⁷⁷Lu]Lu-DOTATATE RLT is safe and well tolerated despite some minor (grade 1) hematological toxicity. Full article