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Cancers
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Hematologic Malignancies and Related Disorders: Challenges from Diagnosis to Treatment
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Hematologic Malignancies and Related Disorders: Challenges from Diagnosis to Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 9010

Special Issue Editors

Dr. Ioanna Sakellari

E-Mail Website
Guest Editor
Hematology Department—BMT Unit, G. Papanicolaou Hospital, 57010 Thessaloniki, Greece
Interests: hematopoietic cell transplantation; cell therapy; acute myeloid leukemia; graft-versus-host-disease
Special Issues, Collections and Topics in MDPI journals
Dr. Eleni Gavriilaki

E-Mail Website
Guest Editor
Second Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
Interests: hematologic malignancies; thrombosis; complement; cellular therapy; lymphoma; myeloma; COVID-19
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hematologic malignancies represent a constantly changing landscape with promising diagnostic and treatment modalities. Emerging challenges in the field involve not only new treatments and appropriate patient selection but also unprecedented worldwide changes, such as COVID-19.

Therefore, this Special Issue aims to highlight basic, translational, and clinical research in the field, gathering both original research and review articles. We welcome physicians and scientists to share their valuable research with us.

Dr. Ioanna Sakellari
Dr. Eleni Gavriilaki
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hematopoietic cell transplantation
  • cell therapy
  • acute myeloid leukemia
  • graft-versus-host disease
  • hematologic malignancies
  • thrombosis
  • complement
  • lymphoma
  • myeloma
  • COVID-19

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Published Papers (6 papers)

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Research

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19 pages, 305 KiB  
Article
Analysis of Stereotyped B-Cell Receptor Frequencies Among Portuguese De Novo-Diagnosed Chronic Lymphocytic Leukemia Patients (PAIS Study)
by Daniela Alves, Gisela Ferreira, Joana Caldas, Mariana Fernandes, Cátia Gaspar, Mafalda Alpoim, Inês Carvalhais, Sara Duarte, Helena Silva, Ana Montalvão, Fernanda Vargas, Teresa Ribeiro, Ana António, Rita Coutinho, Francisca Miranda, Tânia Maia, Marta Gomes, José Carda, Sónia Matos, Rita Jaime and João Raposoadd Show full author list remove Hide full author list
Cancers 2025, 17(8), 1316; https://doi.org/10.3390/cancers17081316 - 14 Apr 2025
Viewed by 292
Abstract
Background/Objectives: Chronic lymphocytic leukemia (CLL) exhibits a heterogeneous clinical course influenced by genetic factors, such as the mutational status of immunoglobulin variable regions (IGHV). Recently, B-cell receptor (BcR) stereotypes have shown promising prognostic value, potentially surpassing IGHV status. The PAIS study [...] Read more.
Background/Objectives: Chronic lymphocytic leukemia (CLL) exhibits a heterogeneous clinical course influenced by genetic factors, such as the mutational status of immunoglobulin variable regions (IGHV). Recently, B-cell receptor (BcR) stereotypes have shown promising prognostic value, potentially surpassing IGHV status. The PAIS study analyzed BcR stereotypes and IGHV mutations in newly diagnosed Portuguese CLL patients to assess prognostic characteristics and disease progression. Methods: This cross-sectional study included 463 adult patients from 15 Portuguese centers, recruited between November 2020 and September 2023. The median age at diagnosis was 70.4 years. The most common clinical stages were 0 (54%) and 1 (32.83%). Results: A total of 15 different BcR stereotypes were identified in the cohort studied. Subtype #1, associated with a poorer prognosis, was the most prevalent, observed in 3.90% of newly diagnosed Portuguese CLL patients. Considering the 19 major stereotypes that could be assigned by the ARResT subsets tool, most patients exhibited a heterogeneous BcR profile (90.14%). A total of 57.24% of patients had mutated IGHV. The concentration of β2-microglobulin was significantly lower in patients with mutated IGHV (2.6 mg/L vs. 3.6 mg/L, p < 0.001). Clinical stage, assessed by the RAI staging system, differed between subgroups, with a higher frequency of stage 0 in patients with mutated IGHV and stage 2 in unmutated patients (p = 0.009). Conclusions: The PAIS study highlighted the predominance of a heterogeneous BcR profile in Portuguese CLL patients. The higher percentage of patients with mutated IGHV at diagnosis supports prior findings. This study improves the characterization of the 10% of Portuguese CLL patients with major BcR stereotypes, offering healthcare providers better predictive power for disease progression and potentially impacting clinical decision making. Full article
(This article belongs to the Special Issue Hematologic Malignancies and Related Disorders: Challenges from Diagnosis to Treatment)
10 pages, 204 KiB  
Article
Cancer-Associated Venous Thromboembolism Among Hospitalized Patients with Solid and Hematological Malignancies: A Comprehensive National Study
by Zaid Khamis, Ghada Araji, Ibrahim Al Saidi, Marian Araji, Chapman Wei, Ahmad Mustafa, Salim Barakat, Varun Chowdhry and Marcel Odaimi
Cancers 2025, 17(5), 729; https://doi.org/10.3390/cancers17050729 - 21 Feb 2025
Viewed by 527
Abstract
Introduction: Venous thromboembolism (VTE) is a major cause of non-cancer-related mortality in cancer patients. Understanding how demographic factors and cancer types influence VTE risk is critical for developing prevention strategies. This study investigates the incidence of VTE in a large cancer patient population, [...] Read more.
Introduction: Venous thromboembolism (VTE) is a major cause of non-cancer-related mortality in cancer patients. Understanding how demographic factors and cancer types influence VTE risk is critical for developing prevention strategies. This study investigates the incidence of VTE in a large cancer patient population, focusing on gender, race, and differences between solid and hematological malignancies. Methods: Data from the National Inpatient Sample (NIS) database were used to identify cancer patients diagnosed with acute VTE. The patients were divided into those with solid and hematological cancers. Key demographic and clinical characteristics were collected, and patients were matched 1:1 using propensity scoring. Statistical analyses, including logistic regression, assessed VTE incidence and its associations with demographic and cancer type variables. A p-value of <0.05 indicated statistical significance. Results: Out of 1,233,832 cancer patients, 63,505 (5.1%) were diagnosed with acute VTE. Females had a higher VTE rate than males (5.5% vs. 4.8%, p < 0.001). Racial disparities showed Black patients with the highest incidence (6.4%), followed by White patients (5%). Patients with solid malignancies exhibited a significantly higher incidence of VTE compared to those with hematological malignancies (5.4% vs. 4.1%; p < 0.001), with lung cancer and non-Hodgkin lymphoma mostly associated with VTE. Conclusions: This study identifies demographic and cancer-specific differences in VTE risk, emphasizing the need for personalized prevention. High-risk groups, including those with solid tumors, females, and Black patients, may benefit from targeted strategies to reduce the burden of VTE and improve cancer outcomes. Full article
(This article belongs to the Special Issue Hematologic Malignancies and Related Disorders: Challenges from Diagnosis to Treatment)
11 pages, 421 KiB  
Article
Cladribine-Based Therapy for Acute Myeloid Leukemia in Child, Adolescent, and Early Young Adult Patients: The MD Anderson Cancer Center Experience
by David McCall, Shaikha Alqahtani, Moriah Budak, Irtiza Sheikh, Aaron E. Fan, Ramya Ramakrishnan, Cesar Nunez, Michael Roth, Miriam B. Garcia, Amber Gibson, Naval Daver, Sofia Garces, Nicholas J. Short, Ghayas C. Issa, Farhad Ravandi, Courtney D. DiNardo, Guillermo Montalban Bravo, Guillermo Garcia-Manero, Branko Cuglievan and Tapan Kadia
Cancers 2024, 16(22), 3886; https://doi.org/10.3390/cancers16223886 - 20 Nov 2024
Viewed by 1237
Abstract
Background: Cladribine-based combination chemotherapy has demonstrated promising efficacy in patients with relapsed/refractory adult acute myeloid leukemia (AML), prompting its increased utilization in the frontline; in pediatrics, it has been typically reserved for relapsed or refractory cases. While fludarabine has been used more commonly [...] Read more.
Background: Cladribine-based combination chemotherapy has demonstrated promising efficacy in patients with relapsed/refractory adult acute myeloid leukemia (AML), prompting its increased utilization in the frontline; in pediatrics, it has been typically reserved for relapsed or refractory cases. While fludarabine has been used more commonly as a purine analog in intensive regimens, cladribine may be an important alternative. Methods: We performed a retrospective study at MD Anderson Cancer Center from January 2015 to July 2023, which included patients aged 1–21 years with refractory or relapsed AML who received cladribine outside of a transplant conditioning. Results: A total of 30 patients were included, with a median age of 20 years (range, 2–21), and 55% being male. Similar to adults, cladribine exhibited good tolerability in pediatric and adolescent patients, with the most common adverse events being febrile neutropenia and myelosuppression. The most common grade 3 or 4 adverse events included febrile neutropenia (55%) and sepsis (26%), and there were no treatment discontinuations due to adverse events. Among patients with a median number of 2 (0–7) prior treatments, the overall response rate (CR/CRi) was 45%, and median event-free and overall survival were 6 and 12 months, respectively. Disease progression resulted in 4 deaths within 30 days of treatment. Conclusions: Cladribine was tolerated in pediatrics. No new safety signals were seen with cladribine regimens in this cohort. Response assessment is limited due to the heavily pretreated cohort. Further prospective studies are warranted on the safety and efficacy of cladribine and establish its role in pediatric, adolescent, and early young adult patients with AML. Full article
(This article belongs to the Special Issue Hematologic Malignancies and Related Disorders: Challenges from Diagnosis to Treatment)
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12 pages, 999 KiB  
Article
The Impact of FDA-Approved Novel Agents for Steroid-Refractory Chronic Graft vs. Host Disease on Treatment Patterns and Outcomes—A Single-Center Longitudinal Cohort Analysis
by Gil Fridberg, Odelia Amit, Chen Karni, Dina Tshernichovsky, David Shasha, Vanessa Rouach, David Varssano, Amir Bar-Shai, Ilan Goldberg, Gilad Wasserman, Irit Avivi and Ron Ram
Cancers 2024, 16(20), 3521; https://doi.org/10.3390/cancers16203521 - 17 Oct 2024
Viewed by 1082
Abstract
Objectives—chronic graft vs. host disease (cGVHD) is associated with substantial morbidity and mortality. We aimed to analyze advances in treatment strategy and outcomes during the last decade due to the incorporation of novel immunosuppressive therapy (IST) drugs in the armamentarium. Methods—we [...] Read more.
Objectives—chronic graft vs. host disease (cGVHD) is associated with substantial morbidity and mortality. We aimed to analyze advances in treatment strategy and outcomes during the last decade due to the incorporation of novel immunosuppressive therapy (IST) drugs in the armamentarium. Methods—we retrospectively analyzed all patients > 18 years with cGVHD after their first hematopoietic cell transplantation (HCT) between 2012 and 2020 (n = 91), divided into three treatment periods: 2012–2014, 2015–2017, and 2018–2020 (groups 1, 2, and 3, respectively). Results—mean cumulative steroid dose and dose/total cGVHD-treatment days was lower in groups 2–3 compared to 1 (p = 0.008 and p = 0.042, respectively). The median IST-free survival was 79 (95%CI54–94) months, with more patients in group 3 (47% (95%CI 25–54%) discontinuing IST at 3 years, p = 0.1). Groups 2–3 compared to 1 had better glycemic control (p < 0.01), higher bone density (p = 0.06), and fewer cardiovascular events. The number of admissions/patient dropped from 0.7/year in group 1 to 0.24/year and 0.36/year in groups 2–3, respectively (p = 0.36). Employment reintegration was higher in groups 2–3 compared with 1 (p = 0.05) and so was earlier return to work (p = 0.01). There were no differences in survival outcomes. Conclusions—the incorporation of novel agents appears to be associated with reduced overall steroid burden, improved cGVHD control, and fewer long-term side effects. Full article
(This article belongs to the Special Issue Hematologic Malignancies and Related Disorders: Challenges from Diagnosis to Treatment)
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Review

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21 pages, 630 KiB  
Review
Comprehensive Review of Early and Late Toxicities in CAR T-Cell Therapy and Bispecific Antibody Treatments for Hematologic Malignancies
by Ayrton Bangolo, Behzad Amoozgar, Charlene Mansour, Lili Zhang, Sarvarinder Gill, Andrew Ip and Christina Cho
Cancers 2025, 17(2), 282; https://doi.org/10.3390/cancers17020282 - 17 Jan 2025
Cited by 1 | Viewed by 2797
Abstract
Chimeric antigen receptor T-cell (or CAR-T) therapy and bispecific antibodies (BsAbs) have revolutionized the treatment of hematologic malignancies, offering new options for relapsed or refractory cases. However, these therapies carry risks of early complications, such as cytokine release syndrome (CRS) and immune effector [...] Read more.
Chimeric antigen receptor T-cell (or CAR-T) therapy and bispecific antibodies (BsAbs) have revolutionized the treatment of hematologic malignancies, offering new options for relapsed or refractory cases. However, these therapies carry risks of early complications, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and delayed issues like graft-versus-host disease (GVHD), infections, and secondary cancers. Effective management requires early diagnosis using advanced biomarkers and imaging, along with prompt interventions involving immunosuppressants, corticosteroids, and cytokine inhibitors. A multidisciplinary approach is essential, integrating hematologists, oncologists, and infectious disease specialists, with emerging strategies like targeted biologics and personalized medicine showing promise in balancing efficacy with toxicity management. Ongoing research is critical to refine diagnostics and treatments, ensuring that these therapies not only extend survival but also improve patients’ quality of life. This review provides critical insights for healthcare professionals to quickly recognize and treat complications of CAR-T and BsAbs therapies. By focusing on early detection through biomarkers and imaging and outlining timely therapeutic interventions, it aims to equip the multidisciplinary care team with the knowledge necessary to manage the challenges of these advanced treatments effectively, ultimately optimizing patient outcomes. Full article
(This article belongs to the Special Issue Hematologic Malignancies and Related Disorders: Challenges from Diagnosis to Treatment)
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Other

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16 pages, 1254 KiB  
Systematic Review
Cardiotoxicity in Acute Myeloid Leukemia in Adults: A Scoping Study
by Ioannis Konstantinidis, Sophia Tsokkou, Savvas Grigoriadis, Lalayianni Chrysavgi and Eleni Gavriilaki
Cancers 2024, 16(13), 2474; https://doi.org/10.3390/cancers16132474 - 6 Jul 2024
Cited by 3 | Viewed by 2331
Abstract
Introduction: According to the National Cancer Institute of the NIH, acute myeloid leukemia (AML) is a rapidly growing cancer with a large quantity of myeloblasts. AML is most often observed in adults over the age of 35, accounting for 1% of all cancer [...] Read more.
Introduction: According to the National Cancer Institute of the NIH, acute myeloid leukemia (AML) is a rapidly growing cancer with a large quantity of myeloblasts. AML is most often observed in adults over the age of 35, accounting for 1% of all cancer types. In 2023, the number of new cases being reported was estimated to reach around 20,380 in total and the rate of mortality in the same year was 1.9%, or 11,310 cases, in the US. Purpose: This scoping study aims to extensively assess and explore the degree of cardiotoxicity in patients with AML that can be caused due to pharmaceutical treatments prescribed by hematologists. This is achieved by performing extensive searches of different scientific databases including PubMed, Scopus, and ScienceDirect. Results: A variety of options are available that are summarized in tables included herein, with each having their advantages and risks of adverse effects, among these being cardiotoxicity. Important medications found to play a significant role include gemtuzumab ozogamicin, venetoclax, and vyxeos. Conclusions: It is understandable that being familiar with all the treatment options available and every potential adverse effect is impossible. However, hematologists and, in general, physicians must try to be updated with the most recent information released to improve the quality of life of their patients and minimize the risk of additional complications. Full article
(This article belongs to the Special Issue Hematologic Malignancies and Related Disorders: Challenges from Diagnosis to Treatment)
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