Journal Description
Hemato
Hemato
- formerly Bloods - is an international, peer-reviewed, open access journal on hematology, published quarterly online by MDPI. The Spanish Society of Hematology and Hemotherapy (SEHH) and the Nuclear Medicine Discovery (Nu.Me.D.) are affiliated with Hemato and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), Scopus, EBSCO, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 33.8 days after submission; acceptance to publication is undertaken in 2.5 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
- Journal Clusters of Hematology: Hemato, Hematology Reports, Thalassemia Reports and Journal of Clinical Medicine.
Impact Factor:
1.0 (2024)
Latest Articles
What Is Still Unclear or Unresolved in Classic Hodgkin Lymphoma Pathobiology, Diagnosis, and Treatment
Hemato 2025, 6(3), 20; https://doi.org/10.3390/hemato6030020 - 4 Jul 2025
Abstract
►
Show Figures
In recent decades, significant progress in medicine has improved the outcomes for Hodgkin lymphoma (HL), a malignancy affecting approximately 8570 new patients annually in the United States and causing around 910 deaths per year [...]
Full article
Open AccessArticle
Intrachromosomal Amplification of Chromosome 21 (iAMP21) Impacts Event-Free Survival but Not Overall Survival Among Pediatric Patients with Acute Lymphoblastic Leukemia: A Single-Center Experience Using an Asparaginase-Intensified Spanish Regimen
by
María Hidalgo, Eduardo Ramos-Elbal, José Antonio Galián, Helios Martínez-Banaclocha, Mercedes Plaza, Victoria Martínez-Sánchez, Ana María Galera, Irene Jiménez, María Esther Llinares, Mar Bermúdez, Alfredo Minguela and José Luis Fuster
Hemato 2025, 6(3), 19; https://doi.org/10.3390/hemato6030019 - 27 Jun 2025
Abstract
Background/Objectives: Intrachromosomal amplification of chromosome 21 (iAMP21) represents a rare and heterogeneous distinct cytogenetic subgroup of B-cell precursor acute lymphoblastic leukemia (ALL) initially associated with a poor prognosis. Treatment intensification with additional doses of methotrexate and asparaginase was associated with better treatment outcomes.
[...] Read more.
Background/Objectives: Intrachromosomal amplification of chromosome 21 (iAMP21) represents a rare and heterogeneous distinct cytogenetic subgroup of B-cell precursor acute lymphoblastic leukemia (ALL) initially associated with a poor prognosis. Treatment intensification with additional doses of methotrexate and asparaginase was associated with better treatment outcomes. Methods: In this retrospective single-center study, we evaluated the impact of iAMP21 on treatment outcome in a cohort of pediatric patients treated with an intensified asparaginase regimen and describe the genomic landscape of four patients with iAMP21. Results: Four out of 89 patients > 1 year old were classified as iAMP21 positive. Five-year event-free survival (EFS) was inferior in the iAMP21-positive group: 25% versus 85.6% (p = 0.001). The cumulative incidence of relapse and treatment-related mortality were 50% vs. 9.9% and 0% vs. 2.38%, respectively, in the iAMP21-positive and non-iAMP21 groups (p = 0.02 and 0.76, respectively). These results did not translate into a significant difference in overall survival: 100% vs. 93.7% (p = 0.6). The presence of iAMP21 (HR 7.68, 95% CI 2.04–29.05; p = 0.002) and a measurable residual disease ≥1% after induction on day +33 (HR 8.82, 95% CI 2.6–29.91; p = 0.001) retained significant negative impact on EFS in multivariate analysis. Conclusions: We found an independent significant prognostic impact of iAMP21 on EFS among pediatric patients with ALL, and clinical presentation and early treatment response did not classify these patients as HR. Diverse genetic backgrounds among iAMP21-positive patients might influence the treatment response and outcome of this heterogeneous disease.
Full article
(This article belongs to the Section Leukemias)
►▼
Show Figures

Figure 1
Open AccessCase Report
Diagnosis and Treatment of Langerhans Cell Sarcoma: A Case Report and Review of the Literature
by
Giulia Pileggi, Sabrina Mariani, Valentina De Santis, Gianluca Maiorana, Federica Lubrano Lobianco, Chiara Togni, Monica Piedimonte, Caterina Tatarelli, Esmeralda Conte, Arianna di Napoli, Emanuela Pilozzi, Evelina Rogges, Agostino Tafuri and Giovanna Palumbo
Hemato 2025, 6(3), 18; https://doi.org/10.3390/hemato6030018 - 26 Jun 2025
Abstract
Langerhans cell sarcoma (LCS) is a rare and aggressive neoplasm characterized by a clonal proliferation of Langerhans cells (LCs), with multi-organ involvement and poor prognosis. Diagnostic challenges arise from its rarity and overlapping features with Langerhans cell histiocytosis (LCH), requiring immunophenotypic and histological
[...] Read more.
Langerhans cell sarcoma (LCS) is a rare and aggressive neoplasm characterized by a clonal proliferation of Langerhans cells (LCs), with multi-organ involvement and poor prognosis. Diagnostic challenges arise from its rarity and overlapping features with Langerhans cell histiocytosis (LCH), requiring immunophenotypic and histological analysis for differentiation. This case report discusses a 67-year-old male with multi-organ LCS involvement. Diagnosis was confirmed via liver biopsy and genetic analysis, revealing a MAP2K1 mutation. Treatment with subcutaneous cladribine and dexamethasone resulted in significant clinical and radiological improvement, despite hematological toxicity due to an underlying myelodysplastic neoplasm (MDS). This case proves the potential efficacy of cladribine for disseminated LCS and highlights the necessity for further research into optimal therapeutic approaches for this rare malignancy.
Full article
(This article belongs to the Special Issue Hematopathology: Rare Hematological Diseases)
►▼
Show Figures

Figure 1
Open AccessReview
Myeloid and Lymphoid Malignancies with Fusion Kinases Involving Spleen Tyrosine Kinase (SYK)—Emerging Rare Entities?
by
Velizar Shivarov and Stefan Lozenov
Hemato 2025, 6(2), 17; https://doi.org/10.3390/hemato6020017 - 14 Jun 2025
Abstract
►▼
Show Figures
Myeloid/lymphoid neoplasms with tyrosine kinase gene fusions (MLN-TK) represent a distinct group of hematologic malignancies recognized in the latest WHO classification due to shared clinical, morphological, and molecular features, and their responsiveness to tyrosine kinase inhibitors (TKIs). Among these, fusions involving the SYK
[...] Read more.
Myeloid/lymphoid neoplasms with tyrosine kinase gene fusions (MLN-TK) represent a distinct group of hematologic malignancies recognized in the latest WHO classification due to shared clinical, morphological, and molecular features, and their responsiveness to tyrosine kinase inhibitors (TKIs). Among these, fusions involving the SYK gene, such as ETV6::SYK and ITK::SYK, have emerged as rare but potentially targetable genetic events in both myeloid and lymphoid neoplasms. SYK, a non-receptor tyrosine kinase critical for hematopoietic signalling, can become constitutively activated through gene fusions, driving oncogenesis via the PI3K/AKT, MAPK, and JAK-STAT pathways. ETV6::SYK has been primarily associated with myeloid neoplasms, often presenting with eosinophilia, bone marrow dysplasia, and skin involvement. In vitro and in vivo models confirm its leukemogenic potential and identify SYK as a therapeutic target. Although SYK inhibitors like fostamatinib have shown transient efficacy, resistance mechanisms, possibly involving alternative pathway activation, remain a challenge. The ITK::SYK fusion, on the other hand, has been identified in peripheral T-cell lymphomas, particularly of the follicular helper T-cell subtype, with similar pathway activation and potential for targeted intervention. Additional rare SYK fusions, such as PML::SYK and CTLC::SYK, have been reported in myeloid neoplasms and juvenile xanthogranuloma, respectively, expanding the spectrum of SYK-driven diseases. Accumulating evidence supports the inclusion of SYK fusions in future classification systems and highlights the need for broader molecular screening and clinical evaluation of SYK-targeted therapies.
Full article

Figure 1
Open AccessBrief Report
Older Jehovah’s Witnesses with Acute Myeloid Leukemia: Hypomethylating Agents and Venetoclax as a Transfusion-Sparing Approach
by
Aditi Sharma, Danielle Blake and Jay Yang
Hemato 2025, 6(2), 16; https://doi.org/10.3390/hemato6020016 - 6 Jun 2025
Abstract
The treatment of acute myeloid leukemia (AML) in Jehovah’s Witness (JW) patients poses unique challenges due to their refusal of blood transfusions. This case series reports the outcomes of four older JW patients with AML treated with azacitidine (Aza) and venetoclax (Ven), including
[...] Read more.
The treatment of acute myeloid leukemia (AML) in Jehovah’s Witness (JW) patients poses unique challenges due to their refusal of blood transfusions. This case series reports the outcomes of four older JW patients with AML treated with azacitidine (Aza) and venetoclax (Ven), including two with hyperleukocytosis and FLT3-ITD mutations. Three patients achieved initial remission; one of these patients subsequently received gilteritinib in combination with Ven and Aza, also achieving remission. All but one therapy cycle was administered in an outpatient setting, and hematologic recovery occurred in all patients without bleeding, ischemic events, or fungal infections. Three patients experienced disease relapse at 179, 301, and 392 days post-diagnosis, while one patient remains alive 706 days post-diagnosis. This report is among the first to demonstrate that Ven and Aza can safely achieve remissions, some of which were durable, in older JW patients with AML, even those with proliferative features like hyperleukocytosis and FLT3-ITD mutations. Our central finding is that Ven and Aza represent safe and effective transfusion-sparing therapeutic options in this population, with triplet therapy incorporating gilteritinib also proving feasible with dose modifications. These findings underscore the clinical relevance of such approaches, suggesting that transfusion refusal should not preclude treatment initiation, offering meaningful clinical outcomes and potentially enhancing quality of life in this population.
Full article
(This article belongs to the Section Leukemias)
Open AccessCase Report
An Unusual Case of Multifactorial Hemolytic Anemia: A Complex Interaction Between Genetic and Autoimmune Factors
by
Mario Biglietto, Giusy Peluso, Cristina Luise, Diletta Tripi, Maria Francesca Conforti, Valeria Filipponi, Luisa Bizzoni and Stefania Trasarti
Hemato 2025, 6(2), 15; https://doi.org/10.3390/hemato6020015 - 29 May 2025
Abstract
Hemolytic anemias (HAs) encompasses a heterogeneous group of disorders with either congenital or acquired etiologies. We present a complex case of a 27-year-old woman with hemolytic anemia of multifactorial origin, involving both inherited RBC membrane defects and multiple autoimmune comorbidities. Genetic testing identified
[...] Read more.
Hemolytic anemias (HAs) encompasses a heterogeneous group of disorders with either congenital or acquired etiologies. We present a complex case of a 27-year-old woman with hemolytic anemia of multifactorial origin, involving both inherited RBC membrane defects and multiple autoimmune comorbidities. Genetic testing identified heterozygous variants in SPTA1 and SBDS, consistent with carrier status for hereditary elliptocytosis and Shwachman–Diamond syndrome. The patient was also diagnosed with Caspr2-positive Isaacs syndrome, systemic lupus erythematosus, seronegative antiphospholipid syndrome, and anti-aquaporin-4 antibody-positive optic neuritis. Despite extensive immunosuppressive and immunotherapic treatment and splenectomy, the clinical course was marked by recurrent hemolytic crises, thrombotic complications, and progressive neurological involvement, ultimately leading to death. Our experience highlights the challenges posed by the diagnosis and management of HAs, underlining the relevance of a multidisciplinary and personalized approach.
Full article
(This article belongs to the Section Non Neoplastic Blood Disorders)
►▼
Show Figures

Figure 1
Open AccessArticle
BET Protein Inhibition Relieves MDSC-Mediated Immune Suppression in Chronic Lymphocytic Leukemia
by
Erin M. Drengler, Audrey L. Smith, Sydney A. Skupa, Elizabeth Schmitz, Eslam Mohamed and Dalia El-Gamal
Hemato 2025, 6(2), 14; https://doi.org/10.3390/hemato6020014 - 24 May 2025
Abstract
►▼
Show Figures
Background: Myeloid-derived suppressor cells (MDSCs) contribute to immune suppression observed in chronic lymphocytic leukemia (CLL). MDSCs are immature myeloid cells that are hijacked during development and further reprogrammed by the tumor microenvironment (TME) to harbor immune-suppressive properties and inhibit T-cell functions. Bromodomain
[...] Read more.
Background: Myeloid-derived suppressor cells (MDSCs) contribute to immune suppression observed in chronic lymphocytic leukemia (CLL). MDSCs are immature myeloid cells that are hijacked during development and further reprogrammed by the tumor microenvironment (TME) to harbor immune-suppressive properties and inhibit T-cell functions. Bromodomain and extraterminal domain (BET) proteins, including BRD4, are epigenetic modulators that regulate genes implicated in CLL pathogenesis and TME interactions. Previously, we investigated how the novel BET inhibitor OPN-51107 (OPN5) prevents CLL disease expansion, modulates T-cell immune function, and alters gene expression related to MDSCs. In turn, we hypothesize that BET proteins such as BRD4 regulate MDSC functions, and subsequent pharmacological inhibition of BRD4 will alleviate MDSC-mediated immune suppression in CLL. Methods: Utilizing the Eµ-TCL1 mouse model of CLL, we evaluated BRD4 protein expression in MDSCs derived from the bone marrow of transgenic and age-matched wild-type (WT) mice. We then investigated the ex vivo functionality of OPN5-treated MDSCs, expanded from Eµ-TCL1 and WT bone marrow in MDSC-supportive medium. Finally, we conducted an in vivo study utilizing the Eµ-TCL1 adoptive transfer mouse model to determine the in vivo effects of OPN5 on MDSCs and other immune populations. Results: Through the course of this study, we found that MDSCs isolated from Eμ-TCL1 mice upregulate BRD4 expression and are more immune-suppressive than their WT counterparts. Furthermore, we demonstrated ex vivo OPN5 treatment reverses the immune-suppressive capacity of MDSCs isolated from leukemic mice, evident via enhanced T-cell proliferation and IFNγ production. Finally, we showed in vivo OPN5 treatment slows CLL disease progression and modulates immune cell populations, including MDSCs. Conclusions: Altogether, these data support BET inhibition as a useful therapeutic approach to reverse MDSC-mediated immune suppression in CLL.
Full article

Figure 1
Open AccessArticle
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
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)
►▼
Show Figures

Figure 1
Open AccessCase 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
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)
►▼
Show Figures

Figure 1
Open AccessCase 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
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)
►▼
Show Figures

Figure 1
Open AccessReview
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
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)
►▼
Show Figures

Figure 1
Open AccessArticle
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
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)
►▼
Show Figures

Figure 1
Open AccessArticle
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
Abstract
►▼
Show Figures
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

Figure 1
Open AccessReview
Arterial Calcification as a Pseudoxanthoma Elasticum-like Manifestation in Beta-Thalassemia: Molecular Mechanisms and Significance
by
Marialuisa Zedde and Rosario Pascarella
Hemato 2025, 6(1), 7; https://doi.org/10.3390/hemato6010007 - 14 Mar 2025
Cited by 1
Abstract
►▼
Show Figures
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
[...] Read more.
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

Figure 1
Open AccessReview
Beyond TKIs: Advancing Therapeutic Frontiers with Immunotherapy, Targeted Agents, and Combination Strategies in Resistant Chronic Myeloid Leukemia
by
Imran Rangraze, Mohamed El-Tanani, Adil Farooq Wali and Manfredi Rizzo
Hemato 2025, 6(1), 6; https://doi.org/10.3390/hemato6010006 - 11 Mar 2025
Abstract
►▼
Show Figures
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
[...] Read more.
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

Figure 1
Open AccessReview
Effect of Omega-3 in Patients Undergoing Bone Marrow Transplantation: A Narrative Review
by
Stefano Mancin, Marco Sguanci, Gaetano Ferrara, Riccardo Caccialanza, Emanuele Cereda, Alessio Lo Cascio, Mauro Parozzi, Fabio Petrelli, Giovanni Cangelosi and Sara Morales Palomares
Hemato 2025, 6(1), 5; https://doi.org/10.3390/hemato6010005 - 26 Feb 2025
Cited by 2
Abstract
►▼
Show Figures
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
[...] Read more.
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

Figure 1
Open AccessReview
Crosstalk Between Coagulopathy and Inflammation in Obesity-Related Severe COVID-19 Infection
by
Nazanin Talebabadi, Eusni Rahayu Mohd Tohit, Maha Abdullah, Siti Yazmin Zahari Sham, Nur Fatin Zalikha Zailan, Syafinaz Amin Nordin, Irmi Zarina Ismail, Ahmad Mahfuz Gazali and Masriana Hassan
Hemato 2025, 6(1), 4; https://doi.org/10.3390/hemato6010004 - 14 Feb 2025
Abstract
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
[...] Read more.
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
(This article belongs to the Section Coagulation)
►▼
Show Figures

Figure 1
Open AccessArticle
Real-World Outcomes of Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Third-Line Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Single-Center Study
by
Aishwarya Sridhar, Thomas S. Gunning, Alexandra Della Pia, Xiaopei Zhang, Jaeil Ahn, Brittany Sinclaire, Brittany Lukasik, Christina Cho, Michele L. Donato, Sukhdeep Kaur, Hyung C. Suh, Lori A. Leslie, Tatyana A. Feldman, Andre H. Goy and Andrew Ip
Hemato 2025, 6(1), 3; https://doi.org/10.3390/hemato6010003 - 28 Jan 2025
Abstract
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
[...] Read more.
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
(This article belongs to the Section Lymphomas)
►▼
Show Figures

Figure 1
Open AccessArticle
Extracorporeal Photopheresis in Graft-Versus-Host Disease: Real-Life Experience Using a New In-Line Method
by
Giulia De Fusco and Gianluca Gessoni
Hemato 2025, 6(1), 2; https://doi.org/10.3390/hemato6010002 - 7 Jan 2025
Abstract
►▼
Show Figures
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:
[...] Read more.
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

Figure 1
Open AccessArticle
Hematological Side Effects of 177Lu-DOTA-TATE Therapy in Patients with NENs
by
Luciano Carideo, Rosaria Meucci, Giuseppe Campagna, Vincenzo Marcello Russo, Enrico D’Ippolito, Maria Rinzivillo, Francesco Panzuto and Daniela Prosperi
Hemato 2025, 6(1), 1; https://doi.org/10.3390/hemato6010001 - 30 Dec 2024
Abstract
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 [
[...] Read more.
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
(This article belongs to the Section Radiolabeled Blood Elements and Other Imaging Modalities)
►▼
Show Figures

Figure 1

Journal Menu
► ▼ Journal Menu-
- Hemato Home
- Aims & Scope
- Editorial Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Editor’s Choice Articles
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Editorial Office
Journal Browser
► ▼ Journal BrowserHighly Accessed Articles
Latest Books
E-Mail Alert
News
Topics

Conferences
Special Issues
Special Issue in
Hemato
Hematopathology: Rare Hematological Diseases
Guest Editor: Pier Paolo PiccalugaDeadline: 15 December 2025
Special Issue in
Hemato
Molecular Mechanisms and Emerging Therapeutics in Multiple Myeloma
Guest Editors: Velizar Shivarov, Jian WuDeadline: 31 January 2026
Special Issue in
Hemato
Memorial Issue Dedicated to Prof. Dr. Michele Baccarani: An Excellent Hematologist on Chronic Myeloid Leukemia
Guest Editors: Domenico Russo, Gianantonio Rosti, Francesco Onida, Jane ApperleyDeadline: 28 February 2026
Topical Collections
Topical Collection in
Hemato
Exclusive Papers of the Editorial Board Members (EBMs) of Hemato
Collection Editors: Antonino Carbone, Laurent Garderet