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Hematol. Rep., Volume 17, Issue 3 (June 2025) – 9 articles

Cover Story (view full-size image): Drug-induced and idiosyncratic cytopenias, including anemia, neutropenia and thrombocytopenia, are challenging due to their unpredictable and multifactorial nature. Causes range from drug reactions to immune dysregulation and unknown mechanisms. Artificial intelligence (AI) offers new opportunities to improve prevention, enhance risk prediction, and engage patients more actively in monitoring. Leveraging AI’s data analysis and machine learning capabilities may help identify risk factors earlier, carry out personalize care, and reduce the incidence and severity of these hematologic complications. View this paper
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8 pages, 475 KiB  
Case Report
Ceftriaxone-Induced Pancytopenia: A Case Report
by Edin Karisik, Zorica Stanojevic-Ristic, Marija Jevtic, Julijana Rasic, Miljana Maric and Milica Popovic
Hematol. Rep. 2025, 17(3), 30; https://doi.org/10.3390/hematolrep17030030 - 12 Jun 2025
Viewed by 328
Abstract
Background: Cephalosporins are considered safe antibiotics. However, serious hematological abnormalities may occur, although rarely, after their therapeutic use. Case Presentation: We present a case of pancytopenia in a 72-year-old female patient treated with ceftriaxone for a urinary tract infection. After five days of [...] Read more.
Background: Cephalosporins are considered safe antibiotics. However, serious hematological abnormalities may occur, although rarely, after their therapeutic use. Case Presentation: We present a case of pancytopenia in a 72-year-old female patient treated with ceftriaxone for a urinary tract infection. After five days of therapy, pancytopenia was observed. Other causes were excluded through extensive diagnostic evaluation, including immunological tests, viral serologies, bone marrow aspiration, and peripheral blood smear. The patient’s clinical condition significantly improved following the discontinuation of ceftriaxone and the administration of granulocyte colony-stimulating factor (G-CSF). Bone marrow findings revealed hypocellularity without malignant infiltration, and peripheral smear showed no dysplasia, blasts, or hemolysis. Conclusions: This case demonstrates that ceftriaxone, although widely regarded as a safe antibiotic, can induce rare but serious hematologic complications such as pancytopenia. A high index of suspicion is required when patients on antibiotic therapy develop unexplained cytopenias. Detailed medication history, exclusion of other causes, and prompt discontinuation of the suspected drug are essential. The patient’s favorable outcome supports the likelihood of an idiosyncratic, immune-mediated mechanism. Future research should explore pharmacogenomic screening in patients at increased risk, particularly involving HLA variants. Full article
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8 pages, 1283 KiB  
Case Report
Multi-Organ Adverse Reaction to Two Hypomethylating Agents: A Challenge in High-Risk Myelodysplastic Syndrome Treatment
by Sofia Brites Alves and Francesca Pierdomenico
Hematol. Rep. 2025, 17(3), 29; https://doi.org/10.3390/hematolrep17030029 - 30 May 2025
Viewed by 252
Abstract
Background and Clinical Significance: Intermediate- to high-risk Myelodysplastic Syndrome (MDS), according to the Revised International Prognostic Scoring System (IPSS-M), confers a high risk of progression into acute myeloid leukemia. Treatment with hypomethylating agents, including azacitidine and decitabine, represents the current standard of care. [...] Read more.
Background and Clinical Significance: Intermediate- to high-risk Myelodysplastic Syndrome (MDS), according to the Revised International Prognostic Scoring System (IPSS-M), confers a high risk of progression into acute myeloid leukemia. Treatment with hypomethylating agents, including azacitidine and decitabine, represents the current standard of care. In eligible patients, hypomethylating agents are used as a bridge for allogeneic stem cell transplantation, currently the only curative approach in these malignancies. The most common side effects of hypomethylating agents are myelosuppression, cutaneous injection site reactions (when azacitidine is given subcutaneously), and gastrointestinal symptoms. Uncommon, disabling, and long-lasting side effects represent a threat to effective treatment in this group of patients. Case Presentation: We describe the case of a 49-year-old male patient with IPSS-M intermediate-risk MDS, intended to receive first-line treatment with azacitidine followed by allogeneic stem cell transplantation. The first, late-onset azacitidine reaction was observed 48 h after the first exposure, with cutaneous and respiratory toxicity, followed by the late-onset recurrence of symptoms after azacitidine withdrawal and decitabine introduction. Conclusions: This case highlights atypical, disabling, and long-lasting drug reactions to two hypomethylating agents, with the persistence of hypersensitivity manifestations months after medication withdrawal. Full article
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8 pages, 748 KiB  
Case Report
Management of Refractory Malignancy-Associated Hemophagocytic Lymphohistiocytosis in Adolescent Patients: A Case Series of Novel Therapeutics and Treatment Challenges
by Meha Krishnareddigari, Kenny Vo and Arun Panigrahi
Hematol. Rep. 2025, 17(3), 28; https://doi.org/10.3390/hematolrep17030028 - 20 May 2025
Viewed by 546
Abstract
Background: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome of immune dysregulation with primary (genetic) and secondary (acquired) forms, including malignancy-associated HLH (m-HLH). The condition often presents significant diagnostic and therapeutic challenges due to overlapping symptoms with underlying malignancies and the absence of [...] Read more.
Background: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome of immune dysregulation with primary (genetic) and secondary (acquired) forms, including malignancy-associated HLH (m-HLH). The condition often presents significant diagnostic and therapeutic challenges due to overlapping symptoms with underlying malignancies and the absence of standardized guidelines for refractory cases. The established standard of care is dexamethasone and etoposide, but no guidelines exist for refractory HLH or cases triggered by malignancy. Case presentations: This case series describes three adolescent patients with m-HLH, focusing on complexities in diagnosis, treatment regimens, and toxicity management. While dexamethasone and etoposide remain a standard of care, their efficacy in refractory cases is limited. We highlight the novel use of targeted therapies, including emapalumab, an interferon-gamma inhibitor, and ruxolitinib, a JAK1/2 inhibitor, which showed potential in modulating immune hyperactivation. Conclusions: Our findings emphasize the need for individualized treatment approaches in adolescent m-HLH and importance of further research to establish evidence-based therapeutic guidelines for refractory cases. Full article
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10 pages, 356 KiB  
Article
Racial Inequities Influencing Admission, Disposition and Hospital Outcomes for Sickle Cell Anemia Patients: Insights from the National Inpatient Sample Database
by Jayalekshmi Jayakumar, Nikhil Vojjala, Manasa Ginjupalli, Fiqe Khan, Meher Ayyazuddin, Davin Turku, Kalaivani Babu, Srinishant Rajarajan, Charmi Bhanushali, Tijin Ann Mathew, Poornima Ramadas and Geeta Krishnamoorty
Hematol. Rep. 2025, 17(3), 27; https://doi.org/10.3390/hematolrep17030027 - 9 May 2025
Viewed by 436
Abstract
Background: Sickle cell disease (SCD) significantly impacts diverse racial groups, particularly African American and Hispanic persons, who experience notable disparities in healthcare outcomes. Despite the extensive literature on SCD, studies focusing on in-hospital racial inequities remain limited. Methods: We conducted a retrospective analysis [...] Read more.
Background: Sickle cell disease (SCD) significantly impacts diverse racial groups, particularly African American and Hispanic persons, who experience notable disparities in healthcare outcomes. Despite the extensive literature on SCD, studies focusing on in-hospital racial inequities remain limited. Methods: We conducted a retrospective analysis using the National Inpatient Sample (NIS) from 2016 to 2020, identifying adult hospitalizations for SCD (HbSS genotype). Hospitalizations were categorized by race—White, African American, Hispanic, and other, and analyzed for demographic variables, admission types, disposition outcomes, and complications. Statistical analyses included chi-square tests and multivariate logistic regression, adjusting for confounders. Results: Of the 1,089,270 identified hospitalizations, 90.31% were African American. African American and Hispanic patients exhibited significantly higher non-elective admissions compared to Whites (77.81%). In-hospital mortality was highest among Hispanics (0.82%). Multivariate regression analysis revealed that African Americans and others had higher odds of prolonged hospital stays (Adjusted Odds Ratio (AOR): 1.30 and 1.20, respectively). African Americans and Hispanics also had increased risks of in-hospital complications of SCD. Conclusions: This study highlights substantial racial disparities in SCD hospitalizations, with African Americans and Hispanics facing poorer outcomes compared to Whites. Hispanics also demonstrated increased mortality. These findings underscore the need for targeted healthcare interventions to address racial inequities in SCD management and improve outcomes for all affected populations. Full article
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8 pages, 1036 KiB  
Brief Report
Clinical Outcome and Molecular Profile in Patients with DDX41 Mutation Hot-Spots
by Nadia Toumeh, Yazan Jabban, Ahmad Nanaa, Rong He, David Viswanatha, Dragan Jevremovic, James M. Foran, Cecilia Y. Arana Yi, Antoine N. Saliba, Mehrdad Hefazi Torghabeh, William J. Hogan, Mithun V. Shah, Abhishek A. Mangaonkar, Mrinal M. Patnaik, Hassan B. Alkhateeb and Aref Al-Kali
Hematol. Rep. 2025, 17(3), 26; https://doi.org/10.3390/hematolrep17030026 - 8 May 2025
Viewed by 450
Abstract
Background/Objectives: DDX41, DEAD-box RNA helicase 41 gene located on chromosome 5q25.3, is one of the most mutated genes in patients with germline predisposition to myeloid neoplasms. Germline and somatic mutations often have different locations and patterns of mutation, with some hotspots [...] Read more.
Background/Objectives: DDX41, DEAD-box RNA helicase 41 gene located on chromosome 5q25.3, is one of the most mutated genes in patients with germline predisposition to myeloid neoplasms. Germline and somatic mutations often have different locations and patterns of mutation, with some hotspots displaying diversity based on ethnicity. We aimed to explore clinical outcomes in patients with various DDX41 hot-spot mutations. Methods: This was a retrospective study of patients at Mayo Clinic with DDX41 mutation identified through Next Generation Sequencing (NGS) between 2018 and 2024. We completed unadjusted comparisons using continuous or categorical variables, and survival rates were assessed using the Kaplan–Meier method and cox regression analysis. Results: Overall survival appears to be higher in those with p.M1| when compared to p.Asp140GlyFs*2 and p.Arg525His, with comparable survival between p.Arg525His and p.Asp140GlyFs*2. Among males with p.M1| who underwent bone marrow transplant, those who underwent bone marrow transplant appeared to have lower survival rates, although not statistically significant. Our study was limited by a small sample size, therefore limiting our ability to reach significance. Conclusions: Our findings suggest potential implications for clinical outcomes based on DDX41 mutation hot-spots. Full article
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12 pages, 2274 KiB  
Case Report
Severe Aplastic Anemia Complicated with Fatal Invasive Fungal Infections in a Young Patient Harboring Perforin Gene Polymorphisms
by Maria I. Krithinaki, Ioannis Kokkinakis, Styliani Markatzinou, Christos Masaoutis, Elena Solomou, Ioanna Papakitsou, Nektaria Xirouchaki, Ioannis Liapis, Helen A. Papadaki and Charalampos G. Pontikoglou
Hematol. Rep. 2025, 17(3), 25; https://doi.org/10.3390/hematolrep17030025 - 6 May 2025
Viewed by 568
Abstract
Background: Severe aplastic anemia (SAA) is an uncommon life-threatening disorder characterized by hypocellular bone marrow and pancytopenia. It is typically associated with immune-mediated mechanisms, requiring immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT). Infections, especially invasive fungal infections such as mucormycosis and [...] Read more.
Background: Severe aplastic anemia (SAA) is an uncommon life-threatening disorder characterized by hypocellular bone marrow and pancytopenia. It is typically associated with immune-mediated mechanisms, requiring immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT). Infections, especially invasive fungal infections such as mucormycosis and aspergillosis, constitute principal causes of morbidity and mortality in patients with SAA. Genetic predispositions, including perforin (PRF1) polymorphisms, may further complicate disease outcomes by impairing immune function. Case report: We describe a case of a 36-year-old female patient diagnosed with SAA, for whom IST was considered, due to the unavailability of a matched sibling donor for HSCT. The patient presented with a feverish condition and deep neck space abscesses were revealed by imaging, caused by invasive aspergillosis. To prioritize infection control, IST was postponed and antifungal therapy with abscess drainage was initiated. However, aspergillosis progressed, despite aggressive and prompt treatment, and ultimately resulted in sepsis, multiorgan failure, and death. In addition, mucormycosis was confirmed post-mortem. Two heterozygous PRF1 polymorphisms (c.272C>T and c.900C>T), were identified by genetic testing, which may have contributed to immune dysregulation and fungal dissemination. Conclusions: The complex interplay between managing SAA and addressing invasive fungal infections, which remain a leading cause of mortality in immunocompromised patients, is highlighted in this case. The latter emphasizes the importance of prompt diagnosis and targeted treatment to alleviate infection-related complications while maintaining care continuity for the hematologic disorder. The detection of PRF1 polymorphisms raises questions about their implication in immune regulation and disease trajectory, emphasizing the need for further research in this field. Full article
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11 pages, 247 KiB  
Review
Artificial Intelligence (AI) and Drug-Induced and Idiosyncratic Cytopenia: The Role of AI in Prevention, Prediction, and Patient Participation
by Emmanuel Andrès, Amir El Hassani Hajjam, Frédéric Maloisel, Maria Belén Alonso-Ortiz, Manuel Méndez-Bailón, Thierry Lavigne, Xavier Jannot and Noel Lorenzo-Villalba
Hematol. Rep. 2025, 17(3), 24; https://doi.org/10.3390/hematolrep17030024 - 29 Apr 2025
Viewed by 618
Abstract
Drug-induced and idiosyncratic cytopenias, including anemia, neutropenia, and thrombocytopenia, present significant challenges in fields like immunohematology and internal medicine. These conditions are often unpredictable, multifactorial, and can arise from a complex interplay of drug reactions, immune abnormalities, and other poorly understood mechanisms. In [...] Read more.
Drug-induced and idiosyncratic cytopenias, including anemia, neutropenia, and thrombocytopenia, present significant challenges in fields like immunohematology and internal medicine. These conditions are often unpredictable, multifactorial, and can arise from a complex interplay of drug reactions, immune abnormalities, and other poorly understood mechanisms. In many cases, the precise triggers and underlying factors remain unclear, making diagnosis and management difficult. However, advancements in artificial intelligence (AI) are offering new opportunities to address these challenges. With its ability to process vast amounts of clinical, genomic, and pharmacovigilance data, AI can identify patterns and risk factors that may be missed by traditional methods. Machine learning algorithms can refine predictive models, enabling earlier detection and more accurate risk assessments. Additionally, AI’s role in enhancing patient engagement—through tailored monitoring and personalized treatment strategies—ensures more effective follow-up and improved clinical outcomes for patients at risk of these potentially life-threatening conditions. Through these innovations, AI is paving the way for a more proactive and personalized approach to managing drug-induced cytopenias. Full article
28 pages, 370 KiB  
Review
Primary Mediastinal B-Cell Lymphoma and [18F]FDG PET/CT: What We Learned and What Is New
by Anna Giulia Nappi, Francesco Dondi, Achille Lazzarato, Lorenzo Jonghi-Lavarini, Joana Gorica, Flavia La Torre, Giulia Santo and Alberto Miceli
Hematol. Rep. 2025, 17(3), 23; https://doi.org/10.3390/hematolrep17030023 - 28 Apr 2025
Cited by 1 | Viewed by 665
Abstract
Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare and aggressive non-Hodgkin lymphoma (NHL), considered a specific entity with proper characteristics, therapies, and prognosis. First-line treatment is not unique, and subsequent strategies in case of disease persistence or relapse are the subject of [...] Read more.
Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare and aggressive non-Hodgkin lymphoma (NHL), considered a specific entity with proper characteristics, therapies, and prognosis. First-line treatment is not unique, and subsequent strategies in case of disease persistence or relapse are the subject of debate and studies. In this scenario, [18F]FDG PET/CT plays a pivotal role both in characterizing the mediastinal mass, the main feature of PMLBCL, in staging, in restaging during therapy (interim PET), and at the end of treatment (EoT PET), to guide clinical management and give prognostic insights. The main issue with PMLBCL is distinguishing viable disease from residual fibrotic/inflammatory mass after therapy and, consequently, settling the next clinical strategy. Novel therapeutic approaches are ongoing and associated with the deepening of [18F]FDG PET/CT potentials as a principal tool in this context. In this review, we will explore PMLBCL from a Nuclear Medicine point of view to help clinicians in the management of these patients. Full article
9 pages, 850 KiB  
Case Report
Management of Diffuse Large B-Cell Lymphoma as Post-Transplant Lymphoproliferative Disorder in a Kidney Transplant Recipient: A Case Report
by Salem Alshemmari, Abdulaziz Hamadah, Samar Ousia, Rasha Abdel Tawab Hamed and Hany Zaky
Hematol. Rep. 2025, 17(3), 22; https://doi.org/10.3390/hematolrep17030022 - 23 Apr 2025
Viewed by 544
Abstract
Background and Clinical Significance: Post-transplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation, often associated with prolonged immunosuppression. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype. Managing PTLD requires a balance between reducing immunosuppression and preventing graft rejection. [...] Read more.
Background and Clinical Significance: Post-transplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation, often associated with prolonged immunosuppression. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype. Managing PTLD requires a balance between reducing immunosuppression and preventing graft rejection. Case Presentation: A 41-year-old female kidney transplant recipient developed PTLD eight years post-transplant, presenting with a right submandibular mass. Biopsy confirmed CD20-positive DLBCL. Initial treatment involved reducing immunosuppression and rituximab monotherapy, which failed to prevent disease progression. The patient underwent six cycles of R-CHOP chemotherapy, achieving complete metabolic remission. Relapse occurred twice, with disease progression in the cervical nodes and tonsils. Salvage therapies, including polatuzumab vedotin and rituximab, achieved remission. During a subsequent relapse, loncastuximab tesirine induced metabolic resolution. Compromised renal function limited treatment options and a second renal transplant was delayed, reducing the risk of PTLD recurrence. Conclusions: This case underscores the challenges of managing PTLD in transplant recipients, especially in relapsed/refractory cases. Single-agent rituximab was insufficient, but combination chemotherapy and novel agents like loncastuximab tesirine were effective. Balancing oncologic control and graft preservation remains critical. This case highlights the need for individualized approaches and novel therapies in managing PTLD while addressing the complexities of immunosuppression and organ preservation. Full article
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