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Hemato, Volume 6, Issue 2 (June 2025) – 6 articles

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11 pages, 810 KiB  
Article
Cathepsin B: Plasma Expression and Concentration in Non-Hodgkin Lymphoma Patients
by Zana Radic Savic, Natasa Bogavac-Stanojevic, Dragana Malcic-Zanic, Sinisa Stankovic, Natasa Egeljic-Mihailovic, Đorđe Stojisavljević, Miron Sopić and Bosa Mirjanic-Azaric
Hemato 2025, 6(2), 13; https://doi.org/10.3390/hemato6020013 - 6 May 2025
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Abstract
Numerous studies point to the significance of cathepsin B (CTSB) in the development of carcinoma. Therefore, the aim of this pilot study was to investigate the levels of cathepsin B (CTSB) and the expression of CTSB mRNA in the plasma of non-Hodgkin lymphoma [...] Read more.
Numerous studies point to the significance of cathepsin B (CTSB) in the development of carcinoma. Therefore, the aim of this pilot study was to investigate the levels of cathepsin B (CTSB) and the expression of CTSB mRNA in the plasma of non-Hodgkin lymphoma (NHL) patients. Methods: The study included 44 newly diagnosed NHL patients and 35 healthy volunteers comprising the control group. CTSB in the plasma samples were detected using the enzyme-linked immunosorbent assay (ELISA). Results: The level of CTSB was significantly higher in NHL patients compared to control subjects: 15.28 (11.68–17.23) versus 11.57 (10.12–13.41), p = 0.003. In addition, a positive correlation between plasma CTSB mRNA and CTSB after therapy was observed (rho = 0.591, p = 0.026). Regarding redox parameters, we found a negative correlation between CTSB and the total antioxidant status (TAS) (rho = −0.499, p = 0.035), as well as a positive correlation with the total oxidant status (TOS) (rho = 0.576, p = 0.012). Conclusions: Targeting CTSB might have significant clinical relevance in the diagnostics of NHL. Full article
(This article belongs to the Section Lymphomas)
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8 pages, 8834 KiB  
Case Report
Refractory/Relapsed Classic Hodgkin Lymphoma Mimicking Disseminated Tuberculosis
by Mohamed Nazem Alibrahim, Hussein Hammam, Antonino Carbone, Noor Alsaleh and Annunziata Gloghini
Hemato 2025, 6(2), 12; https://doi.org/10.3390/hemato6020012 - 3 May 2025
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Abstract
Background/Objectives: Classic Hodgkin lymphoma (cHL) is a predominantly curable B-cell malignancy. However, primary refractory and relapsed (R/R) cHL remain therapeutic challenges, especially in regions with high tuberculosis (TB) prevalence, where clinical and radiologic features overlap and can obscure the correct diagnosis. This article, [...] Read more.
Background/Objectives: Classic Hodgkin lymphoma (cHL) is a predominantly curable B-cell malignancy. However, primary refractory and relapsed (R/R) cHL remain therapeutic challenges, especially in regions with high tuberculosis (TB) prevalence, where clinical and radiologic features overlap and can obscure the correct diagnosis. This article, presenting a case of R/R cHL mimicking disseminated TB, reviews the evolving paradigm in R/R cHL management. Methods: A 30-year-old Middle Eastern male with advanced nodular sclerosis cHL initially achieved a complete remission (CR) with escalated BEACOPP chemotherapy. Shortly afterward, he developed respiratory symptoms and diffuse miliary pulmonary nodules, highly suggestive of disseminated TB. Despite extensive negative TB workup, including QuantiFERON-TB Gold testing, sputum acid-fast bacilli (AFB) staining, and PCR, his imaging raised concern for recurrent cHL. Due to the small size and diffuse distribution of nodules, biopsy was unfeasible, prompting empiric salvage therapy with DEHAP-Carbo, brentuximab vedotin (BV), and nivolumab. Results: The rapid and robust metabolic response on PET/CT supported lymphoma relapse rather than TB. Following four cycles of this combined regimen, he proceeded to autologous stem cell transplantation and achieved a second CR. Conclusions: This case highlights the diagnostic difficulties in differentiating cHL relapse from TB in endemic regions, emphasizes the critical role of PET/CT in guiding therapy when histopathological confirmation is impractical, and illustrates the impact of novel immunotherapies in improving outcomes. By underscoring the importance of early diagnostic suspicion and multimodal assessment, this article also reviews the evolving paradigm in R/R cHL management, where personalized approaches and targeted agents increasingly complement or replace traditional chemotherapy regimens. Full article
(This article belongs to the Section Lymphomas)
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9 pages, 6236 KiB  
Case Report
Successful Perioperative Management of Titanium Cranioplasty in a Patient with Severe Hemophilia A
by Gabriela Micurova, Kristina Maria Belakova, Tomas Simurda, Miroslava Drotarova, Jan Stasko and Branislav Kolarovszki
Hemato 2025, 6(2), 11; https://doi.org/10.3390/hemato6020011 - 26 Apr 2025
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Abstract
Background: Hemophilia A is an X-linked recessive bleeding disorder associated with high risk for intracranial hemorrhage, requiring complicated neurosurgical interventions. Perioperative management is based on quick factor replacement therapy, control of hemostasis, and deciding whether surgery will be beneficial. Methods: We report the [...] Read more.
Background: Hemophilia A is an X-linked recessive bleeding disorder associated with high risk for intracranial hemorrhage, requiring complicated neurosurgical interventions. Perioperative management is based on quick factor replacement therapy, control of hemostasis, and deciding whether surgery will be beneficial. Methods: We report the case of a 49-year-old male with severe hemophilia A who had purulent secernation via a skin fistula as a late complication of decompressive craniectomy for epidural hematoma at younger age. Results: Revision surgery was successfully managed with perioperative administration of clotting factor VIII, and the patient showed indications of titanium cranioplasty. Conclusions: A direct preoperative preparation prior to surgery in a postoperative period with controlled hemostasis has been shown to reduce hemorrhagic complications in hemophilic patients, increasing the quality of life and significant neurological complications. Full article
(This article belongs to the Special Issue Hematopathology: Rare Hematological Diseases)
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57 pages, 1714 KiB  
Review
Clonal Hematopoiesis, a Risk Condition for Developing Myeloid Neoplasia
by Ugo Testa, Germana Castelli and Elvira Pelosi
Hemato 2025, 6(2), 10; https://doi.org/10.3390/hemato6020010 - 22 Apr 2025
Viewed by 278
Abstract
Clonal hematopoiesis (CH) is an age-related process in which hematopoietic stem/progenitor cells increase their fitness due to the acquisition of mutations that lead to a proliferative advantage and to clonal expansion. Its frequency increases with age, and it mostly affects people older than [...] Read more.
Clonal hematopoiesis (CH) is an age-related process in which hematopoietic stem/progenitor cells increase their fitness due to the acquisition of mutations that lead to a proliferative advantage and to clonal expansion. Its frequency increases with age, and it mostly affects people older than 70 years. The most mutated genes in CH are epigenetic regulators, DNA damage response genes, and splicing factors, which are all involved in the development of myeloid neoplasia. Some risk factors, including age, smoking, and prior cytotoxic therapy, increase the risk of developing CH or increase the fitness of CH. Various types of CH have been observed, associated or not with cytopenias or monocytosis. CH represents a risk factor for many pathological conditions and particularly for hematologic malignancies. A better understanding of the risks related to CH has triggered the development of research, translational, and clinical programs for the monitoring, prevention, and treatment of CH. Full article
(This article belongs to the Section Leukemias)
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31 pages, 3207 KiB  
Article
Combined Application of CAR-T Cells and Chlorambucil for CLL Treatment: Insights from Nonlinear Dynamical Systems and Model-Based Design for Dose Finding
by Paul A. Valle, Luis N. Coria, Yolocuauhtli Salazar, Corina Plata and Luis A. Ramirez
Hemato 2025, 6(2), 9; https://doi.org/10.3390/hemato6020009 - 10 Apr 2025
Viewed by 689
Abstract
Background: This work presents a mechanistic nonlinear model, formulated as a system of first-order Ordinary Differential Equations, to investigate the dynamics of Chronic Lymphocytic Leukemia (CLL) under combined chemoimmunotherapy using CAR-T cells and chlorambucil. Methods: Leveraging nonlinear dynamical systems theory and a model-based [...] Read more.
Background: This work presents a mechanistic nonlinear model, formulated as a system of first-order Ordinary Differential Equations, to investigate the dynamics of Chronic Lymphocytic Leukemia (CLL) under combined chemoimmunotherapy using CAR-T cells and chlorambucil. Methods: Leveraging nonlinear dynamical systems theory and a model-based design approach, we derive optimal dosing strategies through extensive in silico simulations, providing hemato-oncologists with actionable tools to refine CLL treatment. The model captures the short- and long-term impacts of both therapies on leukemia cell populations, enabling precise predictions of therapeutic outcomes. Results: By analyzing local and global system dynamics, we establish sufficient conditions for dosing and protocol design, offering a framework to optimize therapies based on individual patient responses. Comparisons of dose-escalation and -de-escalation strategies further demonstrate potential trajectories, such as complete eradication, partial response, or relapse, providing data-driven guidance for improving patient care. Conclusions: This study highlights the power of mathematical modeling in blood cancer research, enhancing the development of personalized and effective CLL treatment regimens. Full article
(This article belongs to the Section Leukemias)
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12 pages, 396 KiB  
Article
Acute Leukemia in Children with Down Syndrome: A Report from the Hellenic HESPHO Group
by Evgenia Papakonstantinou, Athanasios Tragiannidis, Mirella Ampatzidou, Nikolaos Katzilakis, Maria Nikita, Georgios Totikidis, Kleoniki I. Athanasiadou, Vasiliki Antari, Charikleia Kelaidi, Iordanis Pelagiadis, Dimitrios Doganis, Margarita Mpaka, Helen Kosmidis, Antonis Kattamis, Eftychia Stiakaki, Vassilios Papadakis, Emmanouel Hatzipantelis and Sophia Polychronopoulou
Hemato 2025, 6(2), 8; https://doi.org/10.3390/hemato6020008 - 5 Apr 2025
Viewed by 233
Abstract
Background/Objectives: Down syndrome (DS), affecting 1 in 1000 births, has been linked to an increased risk of acute leukemia (AL). Patients with DS–acute lymphoblastic leukemia (DS-ALL) have historically had inferior outcomes when they have received risk-adapted therapy. Transient abnormal myelopoiesis (TAM) constitutes a [...] Read more.
Background/Objectives: Down syndrome (DS), affecting 1 in 1000 births, has been linked to an increased risk of acute leukemia (AL). Patients with DS–acute lymphoblastic leukemia (DS-ALL) have historically had inferior outcomes when they have received risk-adapted therapy. Transient abnormal myelopoiesis (TAM) constitutes a transient leukemia with spontaneous remission in the neonatal period or represents a preleukemic state, preceding DS–acute myeloid leukemia (DS-AML). DS-AML has a better prognosis than that of AML without DS (NDS-AML) due to genetic and biological underlying features, a better response to chemotherapeutic agents, and a lower frequency of relapses. Methods: This retrospective cohort study presents the DS-AL outcomes from a nationwide survey in pediatric oncology centers. A total of 20 patients were studied, 10 with DS-ALL, 4 with DS-AML, 5 with TAM, and 1 with DS-AML after TAM, at median follow-ups of 9.25 (0.6–17.42) years and 7.25 (0.25–18.25) years for DS-ALL and DS-AML, respectively. Results: The median age at diagnosis was 4.7 (1.16–13.83) and 1.92 (1.25–3) years for ALL and AML, respectively. All DS-ALL patients had B-cell precursor ALL and achieved complete remission (CR). One patient relapsed and succumbed due to a severe infection. Three DS-AML patients had AMKL. All DS-AML patients achieved CR. One patient with TAM demanded treatment, all achieved CR, and one progressed to DS-AML. The overall survival (OS) was 70% and 80% for DS-ALL and DS-AML. Conclusions: The improved survival rates of our patients have been due to new protocols with less toxic therapies and better supportive care. Full article
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