Hemato, Volume 7, Issue 2 (June 2026) – 14 articles

Flow cytometry is an essential diagnostic method in hematology, and one of its main applications is the assessment of the clonality of mature B cells. We present a case report of a patient referred for the investigation of absolute lymphocytosis. The flow cytometry study revealed an increased percentage of B cells, but it could not establish B-cell clonality, based on the study of surface light chains in combination with the pattern of expression of mature B-cell markers. The diagnosis of Persistent Polyclonal B-cell Lymphocytosis (PPBL) was considered in the differential diagnosis as the mature B cells were found to be immunophenotypically memory B cells. However, due to the markedly elevated count of B cells, molecular testing with Polymerase Chain Reaction (PCR) for B-cell clonality based on IGH (Immunoglobulin Heavy Chain) gene rearrangements was performed, and it revealed the presence of two clones of B cells. Approximately one year later, the same work-up was repeated in the patient’s bone marrow aspirate. By flow cytometry, a distinct clonal B-cell population was isolated, while the molecular testing with PCR for B cell clonality based on IGH heavy-chain gene rearrangements revealed the presence of three clones of B cells. In addition, evaluation of the sample with high-dimensional mass cytometry showed the presence of four major immunophenotypically abnormal B-cell subsets. Full article

We report a female in her late 80s with high-risk pleomorphic mantle cell lymphoma (MCL) harboring germline ATM mutation and 17p deletion who achieved complete metabolic response with zanubrutinib plus rituximab. Serial peripheral blood next-generation sequencing (NGS) during remission revealed emergence of a molecularly distinct pre-leukemic clone characterized by DNMT3A, TET2, and a TP53 point mutation (p.Tyr220Cys)—distinct from the original 17p deletion. Approximately 20 months after MCL diagnosis, she developed acute myeloid leukemia (AML) with FLT3-TKD and NPM1 mutations, confirming transformation of the pre-leukemic clone. Longitudinal VAF tracking demonstrated complete eradication of MCL-associated mutations (ID3, BIRC3) while the myeloid clone expanded. This case provides direct molecular evidence that AML arose from clonal evolution of a pre-existing hematopoietic clone rather than direct MCL transformation, with implications for understanding second malignancies in BTK inhibitor-treated patients. Full article

Background: In hematologic malignancies, treatment allocation and outcome prediction are traditionally driven by clinical and biological parameters. However, growing evidence suggests that non-clinical factors—such as psychosocial context, caregiver availability, organizational support, and digital health integration—play a pivotal role in patients’ ability to tolerate and adhere to complex therapeutic pathways. The concept of “resilience” may offer a more comprehensive framework to capture this multidimensional readiness to treatment. Methods: We conducted a narrative review of the literature focusing on patient and caregiver resilience in hematologic settings. PubMed, Scopus, and Web of Science were searched for studies published in English over the last 15 years, addressing clinical, psychosocial, organizational, and contextual determinants influencing treatment tolerance, continuity of care, and outcomes in hematology. Results: the literature highlights resilience as a dynamic construct shaped by clinical fitness, psychological resources, caregiver competence, social and family context, healthcare system organization, and access to supportive technologies such as telemedicine. Several domains emerged as recurrent determinants of resilience, yet no standardized, integrated assessment tool is currently available in routine hematologic practice. Conclusions: Resilience in hematology should be reframed as a multidimensional, context-dependent construct extending beyond traditional clinical fitness. Incorporating resilience-oriented assessment into clinical workflows may improve treatment personalization, optimize resource allocation, and enhance patient- and caregiver-centered care. Future research should focus on developing pragmatic, clinically applicable tools to operationalize resilience in real-world hematologic settings. Full article

Introduction: The concomitant occurrence of myeloproliferative neoplasms (MPNs) and plasma cell dyscrasias is rare and presents significant diagnostic challenges. Accurate distinction between overlapping features is essential, particularly when bone marrow fibrosis (BMF) is present. Case Description: We report a 57-year-old female, with a 10-year history of thrombocytosis managed with antiplatelet therapy, who presented with anemia and severe lumbar pain. Bone marrow biopsy revealed marked fibrosis, and imaging revealed multiple vertebral lesions. Diagnostic workup identified features consistent with myelofibrosis (MF) and coexisting IgG-Kappa multiple myeloma (MM). Although the patient initially fulfilled WHO criteria for MF, the rapid resolution of fibrosis following first-line plasma-cell-directed therapy suggested a secondary, cytokine-mediated process rather than a true concomitant MPN. Conclusions: This case highlights the importance of an integrated diagnostic approach in patients with overlapping features of hematologic malignancies. Differentiating between MM-associated fibrosis and true concurrent MPN and MM is critical, as misclassification may alter both prognosis and therapeutic strategy. In triple-negative cases, the histologic response to plasma-cell-directed therapy can serve as a key discriminating criterion. Awareness of the potential association between MM with fibrosis and extramedullary disease is also essential for clinical management. This case underscores the importance of an integrated diagnostic approach in patients with overlapping hematologic features. Full article

Background: The associations between mean corpuscular volume (MCV) and leukocyte-derived ratios and chronological aging remain poorly understood. We aimed to evaluate the association between MCV and leukocyte-derived ratios and chronological age in U.S. adults. Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES, n = 9259) and the Health and Aging Brain Study–Health Disparities (HABS-HD, n = 770). Participants were aged ≥20 years, and individuals with hemoglobin levels outside 12–18 g/dL or C-reactive protein (CRP) > 1 mg/dL were excluded. Associations between age and MCV, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-monocyte ratio (NMR), and platelet-to-white blood cell ratio (PWR) were examined using quartile comparisons and multivariable linear regression adjusted for sex, race/ethnicity, CRP, and red cell folate and hemoglobin. Results: In both cohorts, higher quartiles of MCV, NLR, and MLR were associated with older mean age. In adjusted marker-specific models, MCV, NLR, and MLR were each positively associated with chronological age. In composite models, MCV remained independently associated with older age in both NHANES (β = 0.646, 95% CI 0.567–0.725) and HABS–HD (β = 0.300, 95% CI 0.156–0.445). Conclusions: MCV and selected leukocyte-derived ratios are significantly associated with chronological age across two U.S. cohorts, with MCV showing the most consistent independent association. Full article

Survivors of primary gastric lymphoma (PGL) face a significantly elevated and persistent risk of developing second primary malignancies (SPMs), with gastric adenocarcinoma representing the most frequent SPM and standardized incidence ratios reaching up to 16-fold above the general population. This excess risk persists for decades after initial treatment and is associated with increased cause-specific mortality compared to matched primary cancers. Among patients with PGL, approximately 5% develop gastric cancer (with two-thirds being metachronous), and nearly 15% harbor precancerous lesions including atrophic gastritis, intestinal metaplasia, and dysplasia. Beyond gastric malignancies, survivors also experience elevated rates of extra-gastric SPMs, particularly digestive system tumors (43%), respiratory cancers (21%), and urinary tract malignancies (13%). Key risk factors include treatment with immunochemotherapy or radiotherapy, advanced age, male sex, advanced stage at diagnosis, ulcerative-type lymphoma morphology, and persistent Helicobacter pylori (HP) infection. Patients receiving combined chemoradiotherapy demonstrate the highest SPM risk, particularly for gastric and pancreatic cancers. These findings underscore the critical importance of lifelong, risk-adapted surveillance strategies integrating both hematology and gastroenterology follow-up. Annual endoscopic surveillance is recommended for high-risk patients, with intervals adjusted according to lymphoma histology, HP status, and the presence of precancerous gastric lesions. Mandatory HP eradication with confirmation of response is essential for reducing gastric cancer risk. Future research priorities include prospective, standardized studies to better quantify SPM risk, validation of molecular and microbiological biomarkers for individualized risk stratification, and development of predictive models to enable personalized surveillance protocols and improve long-term outcomes in this vulnerable population. Full article

Background: Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous disease characterized by variable clinical outcomes. The introduction of targeted therapies, particularly the BCL-2 inhibitor venetoclax, has significantly improved treatment outcomes in patients with relapsed/refractory (R/R) CLL. However, real-world data on the safety and effectiveness of venetoclax-based regimens remain limited. Methods: In this multicenter retrospective study, 147 adult patients with R/R CLL treated with venetoclax between April 2019 and August 2025 were analyzed. Venetoclax was administered as monotherapy or in combination with rituximab, obinutuzumab, or ibrutinib. Adverse events were graded according to CTCAE v4.0, and treatment responses were assessed based on IWCLL criteria. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were evaluated using Kaplan–Meier analysis. Results: The median age at venetoclax initiation was 64 years, and patients had received a median of two prior lines of therapy. Combination therapy was administered in 78.9% of patients. The overall response rate was 83.0%, including complete remission in 65.3% of patients. Grade ≥ 3 hematologic adverse events included neutropenia (18.4%), thrombocytopenia (14.3%), and anemia (7.5%). Tumor lysis syndrome (TLS) occurred in 28.6% of patients, predominantly during the dose ramp-up phase. At a median follow-up of 61 months, median OS and PFS were both 60 months. Bulky disease was associated with inferior survival outcomes. Conclusions: Venetoclax-based therapy is effective and well tolerated in patients with R/R CLL in a real-world setting. High response rates and durable survival outcomes were observed despite the inclusion of patients with high-risk clinical and biological features. These findings support the use of venetoclax as a key component of modern CLL treatment strategies and highlight the importance of real-world evidence in optimizing patient management. Full article

Blastic plasmocytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy, characterized by the involvement of multiple organs, including the skin, bone marrow and blood, lymph nodes and the central nervous system. According to tumor location, the disease is classified as skin-only, systemic-only, and skin and systemic. The cutaneous manifestations of disease are typical and are represented by violaceous single tumors or multiple plaques present in sun-exposed cutaneous areas. BPDCN is issued from the malignant transformation of dendritic cell progenitors and is diagnosed using the classical immunophenotypes CD123, CD4 and CD56 in addition to specific membrane markers of plasmocytoid dendritic cells. BPDCN is an aggressive disease and is associated with a short survival. Upfront therapies involve either chemotherapy regimens in fit patients and CD123-targeted therapies, including interleukin-3 conjugated with diphtheria toxin (Tagraxofusp, SL-401), or Pivekimab sunirine, an anti-IL-3R-drug conjugate, for both fit and unfit patients. Targeted treatments limit the toxicities of chemotherapy and allow the bridging of a consistent proportion of patients to hematopoietic stem cell transplantation, the only treatment associated with potential long-term survival. Full article

Acute lymphoblastic leukemia (ALL) is a genetically and epigenetically heterogeneous malignant disease characterized by different subtypes with varying sensitivities to conventional chemotherapy. Despite significant improvements in survival rates, relapse remains the primary cause of treatment failure, often associated with intrinsic or acquired drug resistance. First-line therapy at diagnosis represents a major determinant of relapse in ALL. In this study, we performed a transcriptome and drug response profiling analysis to identify subtype-specific cell surface proteins that are overexpressed in patients with poor response to induction therapy. We summarize the current state of knowledge regarding chemotherapy responses, resistance mechanisms to standard cytostatic drugs and the increasing importance of cell biomarkers as predictors of an adverse disease course and potential therapeutic targets. We discuss the results of clinical and molecular studies linking specific genomic alterations—such as KMT2A-rearrangements, Ph-like, DUX4-rearrangements and T-ALL—to drug resistance and highlight surface antigens like CSPG4, HER2, MCAM and ROR1 that define high-risk leukemia phenotypes. The integration of transcriptomic, immunophenotypic and drug response data could enable a new generation of risk-adapted, surface-directed strategies for relapse treatment in ALL. Our analysis therefore provides subtype-specific predictive therapeutic targets for relapse treatment in ALL. Full article

Background: Sepsis remains a leading cause of mortality in the intensive care unit (ICU). Platelets (PLTs) are central to coagulation, inflammation, and the maintenance of endothelial integrity. Although thrombocytopenia is an established prognostic marker in sepsis, alterations in PLT function and morphology may provide additional insight into disease progression. Methods: This retrospective pilot study examined adult ICU patients diagnosed with sepsis or septic shock. Extracted data included demographic characteristics, clinical variables, and laboratory parameters. Platelet function was evaluated using impedance aggregometry and rotational thromboelastometry (ROTEM), while PLT morphology metrics were obtained from complete blood counts. Statistical analyses comprised Spearman’s rank correlation and logistic regression. Results: Twenty patients were included. Platelet aggregation was impaired across ASPI, ADP, and TRAP-6 assays despite normal PLT counts and morphology. ROTEM-derived measure of PLT contribution to clot strength was within normal ranges. No correlations were observed between PLT function and PLT morphology parameters. An inverse correlation was identified between ROTEM-derived PLT contribution to clot strength and SOFA score (r = −0.60, p = 0.03). Neither PLT function nor PLT morphology was associated with ICU mortality. Conclusions: Functional PLT deficits may occur in sepsis in the absence of structural abnormalities. ROTEM-derived PLT contribution to clot strength may inversely reflect sepsis severity. Platelet function parameters appear unlikely to predict short-term mortality in septic patients. Full article

Background/objectives. Clostridioides difficile infection (CDI) remains a major cause of healthcare-associated infectious colitis, particularly among elderly and multimorbid patients. Disease severity and clinical evolution are influenced by the host’s systemic inflammatory response. This study aimed to evaluate the hematological and inflammatory profile of hospitalized CDI patients and to explore the prognostic value of routine laboratory parameters for prolonged hospitalization. Methods. A retrospective observational study was conducted on 50 adult patients hospitalized with laboratory-confirmed CDI (positive glutamate dehydrogenase, antigen and toxins A/B). Hematological parameters (WBC, hemoglobin, RDW) and inflammatory markers (CRP, fibrinogen) were analyzed at admission and discharge. Prolonged hospitalization was defined as length of stay (LOS) > 8 days (cohort median). Multivariable logistic regression was performed to assess admission predictors of prolonged hospitalization, and model discrimination was evaluated using leave-one-out cross-validation (LOOCV). Results. At admission, patients exhibited marked inflammatory activation accompanied by reduced hemoglobin and elevated RDW. Significant correlations were observed between inflammatory markers. All inflammatory and hematologic parameters improved at discharge. In multivariable analysis, lower admission hemoglobin and higher log-transformed CRP showed exploratory associations with prolonged hospitalization. The internally validated model demonstrated moderate discriminative performance (AUC = 0.65). Conclusions. CDI is associated with substantial systemic inflammatory activation and hematologic alterations. While no individual predictor reached statistical significance, the observed effect sizes provide hypothesis-generating estimates to inform future prospective validation studies. Full article

Background: Sickle cell disease (SCD) patients have increased susceptibility to infections, particularly encapsulated bacterial pathogens such as Streptococcus pneumoniae and Haemophilus influenzae type b. Hyposplenism as well as immune defects in SCD result in increased risks for infections; these are the most frequent complications in individuals with SCD. This study was performed within the African Research and Innovative initiative for Sickle cell Education (ARISE, EC GA No 824021) project to develop best practices in the clinical management of SCD. In this retrospective study we aimed to determine the most prevalent reported infections among SCD patients’ records during clinic visits at Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. Methods: The medical records of 1961 paediatric SCD patients from 1998 to 2023 were extracted and reviewed from a pilot electronic registry using a structural query. The data analysed patterns of infections reported during clinic visits at the ABUTH, Zaria, Nigeria. Results: 458 subjects (23.4%) manifesting at least one infection, of whom 392 (19.9%) subjects had a single infection (bacterial or parasitic) and 173 (8.8%) had more than one infection (bacterial and parasitic). Conclusions: Bacterial and parasitic infections are a significant complication of SCD patients attending a tertiary institution in northern Nigeria. Full article

Background: The co-existence of hemophilia and cancer presents one of the most complex clinical scenarios, demanding individualised therapeutic planning to balance oncologic efficacy and hemostatic safety. This study evaluated the ability of two Large Language Models (LLMs)—ChatGPT (GPT-4) and Microsoft Copilot (GPT-4–based)—to generate clinically appropriate recommendations for real cases of hemophilia with concurrent malignancy. Methods: Six consecutive adult cases of hemophilia and cancer, managed at the Hemophilia Centre of Padua, Italy, were selected for evaluation. Identical structured prompts were submitted to both LLMs. Two independent expert clinicians rated the model outputs across five domains (Decision/Rationale, Strategy, Selected Drug, Regimen, and Assessment) using a four-level ordinal scale. Results: LLMs demonstrated uneven performances. Outputs were consistently rated as highly reliable in domains involving high-level synthesis, such as Assessment and Strategy. However, substantial limitations were observed in the clinically demanding domains of Selected Drug and Regimen. Critically, in the Selected Drug domain, there was complete agreement between the two expert raters for neither system. This severe lack of concordance signifies that clinicians assigned different adequacy ratings to the same output in every case, reflecting ambiguity, lack of specificity, and inconsistent clinical interpretability of the drug-related information provided by LLMs. Conclusions: While LLMs possess the capacity for high-level reasoning and strategic planning, their inability to translate principles into precise, consistent, and clinically interpretable therapeutic plans—particularly regarding drug selection and treatment regimens—is a significant constraint. These deficiencies, highlighted by the minimal expert concordance in critical domains, necessitate rigorous clinical validation before the responsible integration of LLMs into the management of this uniquely vulnerable patient population. Full article

Myeloid/lymphoid neoplasms with tyrosine kinase rearrangements (MLN-TKs) are rare clonal eosinophilias driven by PDGFRA, PDGFRB and other kinase fusions, highly sensitive to tyrosine kinase inhibitors. Their detection remains challenging, particularly for cryptic PDGFRA rearrangements. We performed a large multicenter real-world validation of the generic quantitative RT-PCR assay (gPDGFR), which detects 3′ PDGFRA/PDGFRB overexpression independently of fusion partner. A total of 231 consecutive patients with hypereosinophilia from 12 French centers were analyzed, and assay robustness was further assessed in an independent heterogeneous cohort of 102 tyrosine kinase inhibitor (TKI)-treated patients. Twenty-two PDGFR-rearranged cases (14 PDGFRA-r, 8 PDGFRB-r) were identified. The assay demonstrated 100% sensitivity and 100% negative predictive value. For PDGFRA, positive predictive value and specificity reached 100%. In contrast, PDGFRB overexpression showed lower specificity due to borderline false-positive cases, underscoring the need for confirmatory testing. In selected patients, longitudinal gPDGFR kinetics paralleled fusion-specific RT-qPCR, supporting its use for molecular follow-up when dedicated assays are unavailable, although it does not provide quantitative measurable residual disease assessment. Overall, gPDGFR represents a robust, partner-independent first-line screening strategy that can be readily integrated into routine diagnostic workflows to enable timely identification of patients eligible for targeted therapy. Full article