Mediterranean Journal of Hematology and Infectious Diseases
The Mediterranean Journal of Hematology and Infectious Diseases was founded by Giuseppe Leone, Professor of Hematology at the Catholic University of Rome, in 2009, with the collaboration of Prof. Eligio Pizzigallo, Infectivologist, and Prof. Luigi Maria Larocca, Pathologist.
Università Cattolica Sacro Cuore, Rome, Italy
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HEMATOPOIETIC STEM CELL TRANSPLANTATION IN SEVERE PEDIATRIC SICKLE CELL DISEASE: OUTCOME AND LONG-TERM COMPLICATIONS, SAUDI EXPERIENCE AT KING FAISAL SPECIALIST HOSPITAL, RIYADH, SAUDI ARABIA
Background Hematopoietic stem transplantation (HSCT), from matched related donors (MRD) is offered as a curative therapeutic option in children with Sickle cell disease (SCD). Objective We wanted to assess the outcome and long terms complications observed in children undergoing HSCT at a single transplant center in Saudi Arabia. Patients and Methods One-hundred and twenty nine children were transplanted for severe Sickle cell disease (SCD), consecutively during 2006 to 2020 at our center. Main transplant indication was cerebral vasculopathy in 57 (43%) followed by recurrent vaso-occlusive crisis (VOC) in 47 (36%). Median age at transplant was 9.1 years (range, 1.5-13.9 years). All patients received myeloablative conditioning with Busulfan, Cyclophosphamide and Anti T-Lymphocyte Globulin (Grafalon®): BU/CY/ATG in 114 (88.4%), BU/CY in 13 (10%) and other in 2 (2%). Bone marrow was the main stem cell source in 123 (95%). Results All patients showed granulocyte engraftment. Acute graft-versus-host-disease (aGVHD) and chronic GVHD was observed in 26 (20%) and 12 (9%) patients, respectively. At median follow-up of 4.36 years (range, 0.13-15.5 years), 10-year overall survival (OS) and event free survival (EFS) of 94% and 91% was observed. The OS and EFS were significantly better in patients receiving BU/CY/ATG when compared to BU/CY (OS: 97.4%±1.5%, vs. 76.2%±12.1 P=0.003 and EFS: 94.7%±2.1% vs. 76.2%±12.1%, P=0.019). Conclusion HSCT for children with sickle cell disease from fully match siblings offers the best outcome using myeloablative conditioning. However, significant toxicities were observed secondary to myeloablative regimens, in particular long-term complications, which demands exploring the use of less toxic regimens.
Copyright (c) 2025 Abdullah Al-Jefri, Fatema Al-Hashem, Khawar, Amal Al-Seraihy, Ali Al-Ahmari, Ibrahim Ghemlas, Awatif AlAnazi, Hawazen Al-Saedi, Saadiya Khan, Abdulrahman Al-Musa, Mahasen Saleh, Mouhab Ayas http://creativecommons.org/licenses/by-nc/4.0
ANALYSIS OF CLINICAL CHARACTERISTICS AND DIAGNOSTIC EFFICACY OF BLOOD INDICATORS IN NEONATAL SEPSIS WITH DIFFERENT PATHOGENIC BACTERIA
Objective: To investigate the differences in clinical characteristics between Gram-positive and Gram-negative neonatal sepsis (NS). Methods: A retrospective analysis was conducted on a total of 150 patients admitted between March 2019 and March 2024. . The 91 NS patients were divided into Gram-negative bacteria group (n=31) and Gram-positive bacteria group (n=60). Sixty (n=60) non-septic neonates served as controls and general information was collected on all participants. C-reactive protein (CRP), procalcitonin (PCT) and platelets (PLT) were independent influencing factors for differentiating infections caused by the two pathogens. The onset symptoms, strain distribution, and pretreatment various biochemical parameters were compared among the three groups. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy. Results: The proportions of patients with amniotic fluid contamination and fever (body temperature ≥ 38. 0 ℃) were higher in the Gram-negative group than in the Gram-positive group (P=0.023, 0.049). The concentrations for CRP, PCT and PLT were P=0.019, 0.023, 0.030 respectively. ROC curve analysis revealed that the specificity of the combination of CRP, PCT and PLT in diagnosing Gram-negative bacterial infection was 100.00%, and the area under the curve (AUC) was 0.904, which were higher than those of single indicators (P=0.05). Conclusion: There are differences in the expression of CRP, PCT and PLT between Gram-positive and Gram-negative NS. The simultaneous detection of the three has a high diagnostic value in differentiating infections caused by the two pathogens.
Copyright (c) 2025 You-Hong Duan, Pu Guo, You-Bao Liang, Yao Chen, Zi-Yu Chang http://creativecommons.org/licenses/by-nc/4.0
AN INEXPENSIVE CLINICAL-LABORATORY NOMOGRAM TO PREDICT POST-TREATMENT LUNG DESTRUCTION IN PULMONARY TUBERCULOSIS
Background: Post-treatment lung destruction (LD) impairs quality of life in pulmonary tuberculosis (TB) survivors, yet early risk-stratification tools are lacking. We aimed to develop and internally validate a clinical-laboratory nomogram for predicting LD at completion of standard anti-TB therapy. Methods: This retrospective cohort study enrolled 205 adult, drug-naïve TB patients from April 2021 to April 2025. LD was defined by follow-up chest CT showing extensive fibrosis, bronchiectasis with volume loss, or parenchymal destruction. Twenty-two baseline demographic, clinical, laboratory and imaging variables were screened. Least-absolute-shrinkage-and-selection-operator (LASSO) regression (10-fold cross-validation) reduced dimensionality, and stepwise Akaike information criterion guided multivariable logistic regression. Model performance was compared with random-forest (RF) and support-vector-machine (SVM) classifiers. Discrimination (area under the receiver-operating characteristic curve, AUC), calibration (bootstrap-corrected curve, Brier score) and clinical utility (decision-curve analysis, DCA) were assessed; 1,000-sample bootstrap provided internal validation. Results: LD occurred in 61/205 patients (29.8%). Nine predictors—silicosis, drug resistance, symptom-to-treatment delay, lymphocyte count, C-reactive protein, aspartate aminotransferase, γ-glutamyltransferase, albumin, and atelectasis/cavity—constituted the final model. The nomogram demonstrated excellent discrimination (AUC = 0.93, 95% CI 0.897–0.971; optimism-corrected AUC = 0.93) and good calibration (Brier = 0.13). Across risk thresholds of 10–40%, DCA showed a higher net benefit than treat-all or treat-none strategies. Logistic regression was slightly better than RF (AUC = 0.91) and SVM (AUC = 0.92) while retaining interpretability. Conclusions: An inexpensive, easily applicable nomogram integrating routine clinical and laboratory indices accurately predicts post-treatment LD in TB patients. The tool can support personalized follow-up and timely interventions, warranting external validation in multi-center prospective cohorts.
Copyright (c) 2025 Min Xu, Jiahui He, Jianju Feng http://creativecommons.org/licenses/by-nc/4.0
GROUP-BASED TRAJECTORY MODELING OF PLATELET IN PATIENTS WITH APLASTIC ANEMIA: A STUDY BASED ON THE MIMIC DATABASE
Background: The main components that support coagulation and hemostasis are platelets. Nevertheless, there was no sufficient research done on how variations in platelet counts during hospital stays affect aplastic anemia (AA) patients' prognoses. Objective: Using Group-based Trajectory Modeling (GBTM), this study proposed to evaluate the association between alterations in platelet levels and illness risk in patients with AA. Methods: GBTM was used to group AA patients based on changes in platelet levels. Cox regression models were used to evaluate the relationship between platelet levels and the 30-day survival status of patients. Kaplan-Meier (K-M) survival curve analysis was used to assess the impact of platelet transfusion on survival among different trajectory groups of patients. Results: Three trajectory patterns were recognized by GBTM: Class 1, Class 2, and Class 3. Even after controlling for confounding variables, the Cox risk estimates showed that AA patients had a higher chance of surviving in Class 1 (OR>1, P<0.05). Class 2 patients had the greatest survival, according to K-M (Log-rank P<0.001). According to landmark research, Class 1 patients' survival was not improved by platelet transfusion. Conclusion: Patients with AA who had increasing platelet trajectories during their hospital stay had a higher 30-day survival rate; hence, patients with low platelet counts might not be good candidates for platelet transfusion treatment.
Copyright (c) 2025 Lang Peng, Lixin Zou, Xiaoliu Liu http://creativecommons.org/licenses/by-nc/4.0
THE ROLE OF SLC22A4 IN ACUTE MYELOID LEUKEMIA
Objective: This study aimed to explore the role of SLC22A4 (encoding OCTN1, an organic cation transporter) in acute myeloid leukemia (AML) prognosis and therapy. Methods: We analyzed RNA-seq data from 151 TCGA-AML samples and six Gene Expression Omnibus (GEO) datasets (GSE9476, GSE12662, GSE30029, GSE34577, GSE12417, GSE37642), including 62 normal bone marrow samples and 520 AML samples. Weighted gene co-expression network analysis (WGCNA) identified immune-related gene modules. Differential expression analysis, survival analysis (Kaplan-Meier, Cox regression), methylation profiling, immune infiltration (xCell, EPIC), and drug sensitivity correlations were performed. Statistical methods included Wilcoxon rank-sum tests, ROC curves, and LASSO regression. Results: SLC22A4 gene expression was significantly decreased in AML versus normal samples. The high-expression group was associated with better prognosis versus the low-expression group. Gene set enrichment analysis revealed enrichment of the metabolic transport and immune and tumor-related pathways. In addition, SLC22A4 expression was negatively correlated with immune cells (e.g., activated dendritic cells, CD8 T cells). Methylation of SLC22A4 was significantly negatively correlated with expression. Moreover, it was predicted that 5 miRNAs (i.e., hsa-miR-1299, hsa-miR-1910-5p, hsa-miR-3659, hsa-miR-5093, and hsa-miR-6831-3p) could regulate SLC22A4 gene expression. SLC22A4 expression was positively correlated with sensitivity to cyclobenzaprine, hydrochloride, SGX-523, and simvastatin. However, it was negatively correlated with sensitivity to fluorouracil, abexinostat, EMD-534085, hypothemycin, tamoxifen, and sunitinib. Conclusion: SLC22A4 may be useful as a predictor of poor prognosis and a marker of immunologic infiltration or potent molecular-targeted agents in AML.
Copyright (c) 2025 Yingying Li, Yang Li, Wenguo Cheng http://creativecommons.org/licenses/by-nc/4.0
The MINI-POLATUZUMAB VEDOTINE PLUS CHP (POLA-R-CHP) VS. MINI-R-CHOP IN PATIENTS OVER 80 YEARS OF AGE WITH DIFFUSE LARGE B-CELL LYMPHOMA: A RETROSPECTIVE, PROPENSITY SCORE-MATCHED ANALYSIS STRATIFIED BY SIMPLIFIED FRAILTY SCORE
Background: Polatuzumab vedotin (Pola) combined with rituximab, cyclophosphamide, doxorubicin, and prednisolone (PRCHP) is a new standard first-line therapy; however, patients aged >80 years were excluded from the POLARIX trial. This retrospective study evaluated the efficacy and safety of mini-PRCHP and mini-rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) in older patients. Methods: Sixty-three participants aged >80 years were treated with PRCHP, and 76 were treated with RCHOP between January 2018 and December 2024 at our hospital. Propensity score matching (PSM) was performed for Ann Arbor stage, international prognosis index, and frailty score to adjust for baseline differences. Results: After a 1:1 PSM matching, 59 patient pairs were selected (median age: 84 years; p=0.88). Patients were classified as fit (n=9, 15%), unfit (n=21, 36%), or frail (n=29, 49%) according to their frailty scores (p=1.00). The overall response rate (ORR), complete response rate (CRR), overall survival (OS), and progression-free survival (PFS) at 12 months were not significantly different between the mini-PRCHP and mini-RCHOP groups. In patients with frailty, the 12-month PFS was not significantly different (50.9% vs. 53.7%, p=0.87); however, in non-frail patients, the PFS was significantly higher in the mini-PRCHP group than that in the mini-RCHOP group (80.8% vs. 60.1%, p=0.04). Safety profile of grade 3/4 adverse events was similar for both groups; however, peripheral neuropathy was prominent in the mini-RCHOP group (p=0.06). Conclusion: Mini-PRCHP demonstrated efficacy and safety comparable to mini-RCHOP in older patients. Mini-PRCHP may prolong PFS in non-frail patients and reduce the risk of peripheral neuropathy.
Copyright (c) 2025 Shuku Sato http://creativecommons.org/licenses/by-nc/4.0
T-CELL RECEPTOR (TCR)-VΒ REPERTOIRE FLOW CYTOMETRY FOR T-CELL LYMPHOPROLIFERATIVE DISORDER: A RETROSPECTIVE ANALYSIS OF A SINGLE-CENTER REAL-LIFE LABORATORY EXPERIENCE
Background: Discrimination between clonal and reactive cell proliferation is critical for the correct management of T-cell lymphocytosis. Multiparametric flow cytometry (MFC) represents a valuable tool, particularly because it allows to evaluate the T-cell receptor (TCR) Vβ repertoire to pinpoint eventual clonality in T-cell lymphocytosis. A restricted expansion of a single out of the 24 evaluable families or a “clonogram-off” pattern are highly suggestive of the presence of a clonal T-cell population. However, data available on the concordance between MFC TCR-Vβ repertoire and molecular analysis of TCR gene rearrangements, which is regarded as the gold standard for assessing T-cell clonality, are limited. Objective and methods: We performed a retrospective monocentric study including 307 patients referred to our center for lymphocytosis between 2003 and 2024. The aim of our study was to investigate the diagnostic accuracy of MFC TCR-Vβ repertoire analysis and to compare its performance with molecular analysis of TCR gene rearrangements, for the identification of T-cell clonality. Results: MFC TCR-Vβ repertoire analysis demonstrated a restricted expansion of a single Vβ family in 67.5% of cases, while clonality in the remaining 32.5% was inferred by a “clonogram-off” pattern. For 215 (70%) patients both MFC TCR-Vβ repertoire analysis and molecular analysis of TCR gene rearrangements were available, showing an absolute concordance (215 out of 215 cases, 100%) between the two methods. Conclusion: MFC TCR-Vβ repertoire analysis is a rapid, cheap, sensitive, and reliable tool to identify clonal T-cell lymphocytosis. It represents an absolute valid first-line diagnostic approach, and it should be included into the routinely laboratory work-up performed MFC analysis for peripheral lymphocytosis.
Copyright (c) 2025 Marco Antonacci, Jacopo Micozzi, Alessandro Costa, Alessandro Laganà, Maria Laura Milani, Stefania Intoppa, Vittorio Bellomarino, Maria Grazia Nardacci, Mario Biglietto, Stefano Imperatore, Maria Laura Bisegna, Maurizio Martelli, Irene Della Starza, Maria Stefania De Propris http://creativecommons.org/licenses/by-nc/4.0
PREDISPOSING FACTORS TO INFECTIONS IN THALASSEMIA SYNDROME PATIENTS
Introduction: Thalassemia is an inherited blood disorder characterized by defective hemoglobin production, leading to chronic anemia. Patients, particularly those who are transfusion-dependent, face a heightened risk of infections due to disease-related factors like anemia and treatment-related complications such as iron overload and splenectomy. This study explores the factors contributing to infections in thalassemia patients to improve management strategies. Methods: A retrospective analysis was conducted on 303 patients with thalassemia at a tertiary care center from 2007 to 2022. Data were collected on demographics, transfusion dependency, splenectomy status, ferritin levels, vaccination history, and culture results. Logistic regression analysis was used to identify infection risk factors, with significance set at p < 0.05. Results: Out of 303 patients, 72 (23.8%) experienced culture-positive infections, with Escherichia coli being the most isolated pathogen. Patients with infections had significantly higher ferritin levels and were less likely to be on chelation therapy. Combined chelation therapy, however, showed a protective effect (OR: 0.02, p = 0.01). Female patients were more susceptible to infections (OR: 2.94, p = 0.04), while mortality was notably higher in patients with positive cultures (22% vs. 3%, p < 0.001). Conclusion: This study highlights the strong link between iron overload, chelation and risk of infection in thalassemia patients. Effective management, including proper chelation therapy and monitoring ferritin levels, is critical for reducing infections and improving outcomes. Further studies are needed to confirm these findings and guide future management strategies.
Copyright (c) 2025 Eman M Mansory, Lina M. Abdulrahman, Balsam Osman, Sawsan M. Sawsan, Assil F. Ruckn, Marwa Aljedaani, Nemmat Hassan, Ahmed S. Barefah, Hatem M. Alahwal, Yassir Daghistani, Salem M. Bahashwan, Abdullah T. Almohammadi, Osman O. Radhwi http://creativecommons.org/licenses/by-nc/4.0
POST-LOAD PLASMA GLUCOSE INCREASE (PG-GAP) AS A RISK FACTOR FOR DEVELOPING DYSGLYCEMIA IN PATIENTS WITH TRANSFUSION-DEPENDENT Β-THALASSEMIA (Β-TDT): RETROSPECTIVE ANALYSIS OVER 8 YEARS
Abstract. Background: Glucose dysregulation (GD) in transfusion-dependent β-thalassemia (β-TDT) patients demands early detection and intervention. However, current diagnostic criteria of patients with a normal oral glucose tolerance test (OGTT) may fail to detect all high-risk individuals. Objectives: Our objective was to evaluate the incremental rise gap in plasma glucose (PG) during oral glucose tolerance tests (OGTTs), defined as the difference between 2h-PG and fasting PG, as a predictor for the future risk of developing glucose dysregulation (GD) and overt diabetes in patients with transfusion-dependent β-thalassemia (β-TDT) with normal glucose tolerance (NGT) . Research design and methods: 58 β-TDT patients, recruited from three Thalassemia centers (Iran, Italy and Greece), were selected for the study. β-TDT patients were categorized into three groups, based on the difference between 2 h-PG and FPG (2 h-PG – FPG): "Low post-load", when the gap (2-h PG mg/dL - FPG ) was < 20th percentile ( < 10 mg/dL) Group A; "Medium post-load and High post-load" groups, when the differences was distributed between 20th and <75th centile (> 10 mg/dL and < 30 mg/dL (Group B). and ≥75th percentile ( ≥ 30 mg/dL; Group C.). Results: In all 58 β-TDT patients, follow-up was available for 6-years and in 45 patients for 8 years within 2 years interval. The incidence of GD, [isolated high 1-h PG (>155 mg/dL) and Th-RD], after an 8-year follow-up, was significantly lower in Groups A and B (27/45 patients) compared to Group C (18/45 patients) (χ2: 4.8214;P:0.028). Noteworthy, three patients of group C ("High post-load gap") developed thalassemia-related diabetes mellitus (Th-RDM). At last evaluation in 13/45 (28.8%) patients the SF level was < 800 µg/L, in 17/45 (37.7%) between ≥ 800 µg/L and < 1,500 µg/L, in 14/45 (31,1 %) between ≥ 1,500 µg/L and < 3,000 µg/L, and in 1/45 (2.3%) ≥ 3,000 µg/L. Conclusions: Our findings suggest that a high rise of postload plasma glucose gap, above 10 mg/dL, is associated with a progressively increased risk of glucose dysregulation over the next 6- 8-year period. These findings highlight the need for a personalized approach to assess the risk of early glucose metabolic disorders in β-TDT patients who are traditionally classified as normoglycemic.
Copyright (c) 2025 Vincenzo De Sanctis, Mohammad Faranoush, Efthymia Vlachaki, Theodora- Maria Venou, Ashraf T Soliman, Shahina Daar, Ploutarchos Tzoulis, Christos Kattamis http://creativecommons.org/licenses/by-nc/4.0
GREEK CONSENSUS ON CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) TREATMENT
New targeted therapies have revolutionized the treatment landscape in CLL. Biological features, patient characteristics and preferences and the safety profile of each treatment option should be taken into consideration for making the optimal treatment choice.This consensus practice statement on CLL treatment was developed by a group of Greek experts in CLL based on the available evidence for both the first line treatment and for the relapsed/refractory setting.
Copyright (c) 2025 Sotirios Sachanas, Theodoros Vassilakopoulos, Maria Angelopoulou, sotirios Papageorgiou, Emmanouil Spanoudakis, Maria Bouzani, Maria Dimou, Panagiotis Panagiotidis http://creativecommons.org/licenses/by-nc/4.0
VACCINATION FOLLOWING LEUKEMIA TREATMENT: VIRAL VACCINE RESPONSES IN SURVIVORS OF ACUTE LYMPHOBLASTIC LEUKEMIA
Background: Emerging treatment strategies have enhanced life expectancy for cancer patients, but late complications, including vaccine-preventable infections from diminished antibody titers, are common. This study evaluates viral vaccine immunity in children post-leukemia treatment and examines the need for additional vaccine doses and their effectiveness. Methods: Our cohort included 62 children diagnosed with acute leukemia. We recorded patients’ sex, age at diagnosis, type of leukemia, risk groups, vaccination status prior to chemotherapy, and serology results for hepatitis A, hepatitis B, varicella, measles, rubella, and mumps (MMR) both at the end of chemotherapy and after vaccination following chemotherapy. Results: Post-treatment, patients exhibited a loss of protective antibody responses: hepatitis A (44.4%), hepatitis B (67.7%), varicella (62.5%), measles (46.9%), rubella (43.5%), and mumps (50%). Notably, high-risk acute lymphoblastic leukemia (HRG ALL) patients had marked decrease in protective antibodies for hepatitis B, measles, rubella, and mumps compared to standard- and intermediate-risk (SRG/IRG ALL) patients (p<0.05). Among the seronegative patients, following vaccination, five (15.2%) remained seronegative for varicella, one (2.2%) for hepatitis A, one (3.5%) for measles, one (3.8%) for rubella, and two (6.5%) for mumps. Conclusion: Our study highlights a significant loss of vaccine-protective antibody responses after acute leukemia treatment, particularly among HRG. The increased vulnerability to vaccine-preventable infections, particularly hepatitis B, measles, rubella, mumps, and varicella, in HRG ALL patients highlights the importance of ongoing monitoring of immunization status and potential revaccination strategies to ensure adequate protection against infectious diseases.
Copyright (c) 2025 Elif Kilic Konte, Ayca Koca Yozgat, Aysun Kara Uzun, Bahar Cuhaci Cakir, Nese Yarali http://creativecommons.org/licenses/by-nc/4.0
COMPARISON OF IL-34, ELASTOGRAPHY, AND BIOPSY IN THE ASSESSMENT OF LIVER FIBROSIS IN CHRONIC HEPATITIS B
Background: HBV leads to the development of liver fibrosis. Although liver biopsy is considered the gold standard, it is an invasive procedure. This study aimed to compare non-invasive methods, shear wave elastography (SWE) and serum interleukin-34 (IL-34), with liver biopsy pathology results in treatment-naïve CHB patients to assess their reliability in evaluating liver fibrosis. Material and Methods: Between 2021 and 2022, a total of 392 treatment-naïve patients diagnosed with CHB who presented to the infectious diseases outpatient clinic and were evaluated for liver biopsy indication were initially screened. After applying exclusion criteria, 105 patients were included in this prospective study. To determine liver fibrosis, SWE and serum IL-34 levels were compared simultaneously with liver biopsy pathology findings. Results: Among the 105 patients included, 58 (55%) were male, and the mean age was 42.97 years. The median IL-34 level was 10.70 pg/mL in patients with fibrosis ≥2, compared to 6.20 pg/mL in those with fibrosis 0–1. IL-34 levels were found to be significantly associated with advanced stages of fibrosis (p<0.001). According to ROC analysis, the optimal cut-off values for predicting fibrosis≥2 were 8.1 pg/mL for IL-34 (AUC=0.955) and 8.18 kPa for SWE (AUC=0.939). Both IL-34 and SWE demonstrated high sensitivity and specificity in predicting advanced fibrosis and higher necroinflammatory activity. Conclusion: IL-34 and SWE exhibit high diagnostic performance as non-invasive methods for assessing liver fibrosis in CHB patients. The integration of these approaches into clinical practice may significantly reduce the need for biopsy and, due to their repeatability and lower cost, provide substantial advantages in patient management.
Copyright (c) 2025 Vahibe Aydın Sarıkaya, gülşah Tunçer, sevim Özdemir, Rüştü Türkay, Burak Sarıkaya, Saime Gül Barut, Esen Gül Uzuner, Filiz Pehlivanoğlu http://creativecommons.org/licenses/by-nc/4.0
BASELINE THROMBIN GENERATION TEST DOES NOT PREDICT THROMBOTIC EVENTS IN ACUTE LEUKEMIA: A MONOCENTRIC PROSPECTIVE STUDY
Thromboembolic and hemorrhagic complications are significant causes of morbidity and mortality in patients with acute leukemias (AL). While AL is characterized by a complex hemostatic imbalance, conventional coagulation tests and platelet counts offer limited predictive value for bleeding and thrombotic events. Global coagulation assays (GCAs), such as the Thrombin Generation Assay (TGA), provide a more comprehensive assessment of coagulation potential and may offer improved risk stratification. This prospective, single-center pilot study aimed to explore the utility of TGA in newly diagnosed adult patients with AL. Between February 2022 and September 2024, patients were enrolled at the Department of Translational and Precision Medicine, Sapienza University of Rome. Baseline clinical and laboratory data, including TGA parameters, were collected, and patients were monitored for thrombotic events until death or last follow-up. TGA values at diagnosis displayed wide inter-individual and inter-subtype variability. However, no statistically significant association was found between baseline TGA parameters and the development of thrombotic events (p > 0.05). These findings suggest that a single TGA measurement at diagnosis may not predict thrombotic risk in AL patients. Future studies incorporating longitudinal TGA assessments and additional hemostatic evaluations, such as platelet function analysis, may help refine risk prediction for both thrombotic and hemorrhagic complications in this high-risk population.
Copyright (c) 2025 Mario Biglietto, Rosaria Mormile, Maria Laura Bisegna, Alessandro Laganà, Anna Laura Faccini, Andrea Papa, Erminia Baldacci, Cristina Santoro, Maria Stefania De Propris, Antonio Chistolini http://creativecommons.org/licenses/by-nc/4.0
FASTING PLASMA GLUCOSE LEVELS WITHIN THE HIGH NORMAL RANGE ARE ASSOCIATED WITH A SIGNIFICANTLY INCREASED RISK OF FUTURE DYSGLYCEMIA IN TRANSFUSION-DEPENDENT Β THALASSEMIA: A DECADE-LONG MULTICENTER RETROSPECTIVE ANALYSIS
Abstract. Objective: To evaluate the risk of developing glucose dysregulation and diabetes mellitus over a 10-year period among transfusion-dependent β-thalassemia (β-TDT) patients with varying levels of fasting plasma glucose (FPG) within the normoglycemic range. Setting: The study included β-TDT patients followed from January 2014 to January 2025 in three thalassemia canters; Tehran and Shiraz in Iran, and Ferrara in Italy. Participants: A total of 238 β-TDT patients (age range: 10–41.9 years; 96 males and 142 females) were included. Results: At baseline, the mean fasting plasma glucose (FPG) level was 88.0 ± 8.3 mg/dL (median: 90 mg/dL), and the mean serum ferritin (SF) level was 2,080 ± 2,072 µg/L (median: 1,368 µg/L). The mean alanine aminotransferase (ALT) level, available in 201/238 patients, was 29.0 ± 25.8 IU/L. β-TDT patients were categorized into three subgroups according to the conversion of FPG during the 10 year follow up [Group A: 93/238 β-TDT patients with persistent normal FPG according to ADA criteria; Group B: 67/238 patients developed persistent impaired fasting glucose (IFG), and Group C: 78/238 patients developed thalassemia-related diabetes mellitus (Th-RDM)]. Notably, 64.1% and 76.9 of patients with FPG at baseline ≥ 90 mg/dl and < 100 mg/dL developed impaired fasting glucose (Group B) and Th-RDM (Group C), respectively. To determine the optimal cutoff for the risk of progressing to impaired fasting glucose (IFG) and Th-RDM at 10-year follow-up, ROC curve analyses and respective areas under the curve were analyzed. The FPG cutoff value for optimal specificity and sensitivity was established at 87.5 mg/dL. Contributing factors associated with the progression to prediabetes and Th-RDM included: older age, gender (females), positive family history of type 1 or type 2 diabetes, lower pre-transfusion hemoglobin levels, severity of iron overload, and elevated liver enzyme levels. Conclusions: Higher FPG levels within the normoglycemic range in β-TDT patients are associated with a greater risk for future glucose dysregulation and diabetes. Close monitoring and timely intervention in these high-risk individuals should be considered in order to reduce the burden of hyperglycemia in this population.
Copyright (c) 2025 Vincenzo De Sanctis, Forough Saki, Mehran Karimi, Mohammad Faranoush, Ihab Elhakim, Ashraf T Soliman, Shahina Daar, Ploutarchos Tzoulis http://creativecommons.org/licenses/by-nc/4.0
MOLECULAR CHARACTERIZATION OF EPSTEIN - BARR VIRUS BASED ON EBNA3C PROTEIN AMONG HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS IN JORDAN
Background: Epstein-Barr virus (EBV), a human herpes virus, presents significant risks to hematopoietic stem cell transplant (HSCT) recipients due to immunosuppressive treatments. Two genotypes of EBV can infect humans: EBV1 and EBV2. These genotypes differ in their latent genes. One important latent protein is EBNA3, which plays a crucial role in immune evasion and pathogenesis of EBV Objectives: This study characterizes EBV genotypes among HSCT recipients in Jordan and examines the relationship between EBV positivity and demographic factors. Methods: A retrospective observational study was conducted at the Jordanian Royal Medical Services Hospital (JRMS) from January to October 2024. Blood samples were collected from the virology department, and plasma was separated. EBV-DNA detection was performed using quantitative real-time PCR, while conventional PCR targeted EBNA3C genes for genotyping. Results: Out of 93 EBV-positive HSCT recipients, 31 underwent genotyping analysis. The findings revealed a predominance of EBV2, detected in 26 samples (84%), while 5 samples (16%) exhibited mixed infections. Notably, EBV1 was not identified in any samples. A significant association was found between EBV positivity and male recipients, with a markedly higher prevalence in individuals under 18 years of age (P<0.0001). Conclusion: The predominant genotype among HSCT recipients in Jordan was EBV2, with co-infections of EBV1 and EBV2. Understanding the prevalent genotypes in transplant patients is crucial for managing EBV-related complications, ultimately improving patient outcomes. This study highlights the need for continuous monitoring and characterization of EBV genotypes in immunocompromised populations.
Copyright (c) 2025 Rabaa Athamneh, Hiba Swaity, Waleed Almomani, Hayyan. Taweil , Assia Benbraiek, Anas Khalifeh http://creativecommons.org/licenses/by-nc/4.0
SEROLOGICAL AND MOLECULAR DETECTION OF RICKETTSIA SPP STEMMING FROM HEMATOPHAGOUS VECTORS IN PATIENTS WITH MENINGEAL SYNDROME IN NORTHERN ALGERIA
Background: Rickettsioses are considered as emerging or re-emerging hematophagous arthropod-borne zoonosis. In addition Meningeal syndromes are also among the most common reasons for consultation in infectious disease emergency. Objectives: Our study aimed to identify Rickettsia spp in patients presenting with Meningeal Syndrome at the National Centre of Infectious Diseases El-HADI FLICI Hospital, Nicolle-Laveran department in Algiers. Methodes: We collected 55 whole blood and 55 sera from patients with meningeal syndrome; of various ages and genders, with a mean age of 24.03 years (ranging from 2 to 50 years old). Results: The indirect immunofluorescence assay (IFA) for Rickettsia spp returned positive results in seven sera (7/55, 12.72%). We diagnosed four cases of Spotted Mediterranean Fever (MSF) caused by R. conorii, two cases of Murine Typhus caused by R. typhi, and one case of Flea-borne Spotted Fever caused by R. felis. Concerning the spinal Tap, we reported in three patients positive for R. conorii, where cerebrospinal fluid was opalescent and mixed cellular profile on cytology. These findings suggest a possible co-infection with R. conorii in patients with meningeal syndrome.Thus, the serological findings coupled with the Meningeal syndrome, and the diverse clinical manifestations of both pathogens observed among these patients, suggest a possible overlap in clinical expression. Conclusion: These results highlight the importance of heightened awareness among infectious disease specialists, particularly when faced with confirmed cases of Meningeal Syndrome that may exhibit clinical similarities with Rickettsial diseases, especially in regions where hematophagous arthropod-borne zoonoses are prevalent.
Copyright (c) 2025 HICHEM GHAOUI, IBRAHIM Nasir ADAM, BASHER Nosiba, TAKFARINAS IDRES, SORAYA TEMIM, ASMA SAAD-DJABALLAH , IDIR BITAM, NASSIMA ACHOUR http://creativecommons.org/licenses/by-nc/4.0
HEALTH-RELATED QUALITY OF LIFE MEASUREMENT IN ADULTS WITH SICKLE CELL DISEASE IN STEADY STATE: EXPERIENCE OF ONE FRENCH REFERENCE CENTER
Sickle cell disease (SCD) is a genetic disease of public health concern. Adult patients face various disease-related complications, which affect their quality of life (QoL). Few studies have examined relationships between these events and health-related (HR) QoL. We conducted a study of 240 adults with SCD seen in steady state at a routine clinic visit over one year. Two self-administered questionnaires were used to determine patients’ HRQoL: the sickle cell self-efficacy scale (SCSES) and the unspecific SF-36 scoring system evaluating physical and mental components. Factors impacting HRQoL were established using univariate and multivariate regression analyses. Participants had a median age of 28 years (Sex ratio male/female 0.61; 68% SS genotype). Most of them had experienced more than one SCD-related complication and more than one affected organ system. A good correlation was established between the SCD specific and the unspecific scoring systems. Using the SF-36 scoring system, energy/fatigue, general health and pain subscales showed the lowest median scores, while physical functioning had the highest median score. In univariate and multivariate analyses, hospitalization for SCD complications occurring during the last year preceding QoL evaluation was the main feature impacting HRQoL. Good compliance to hydroxyurea (HU) therapy was associated with higher SCSES and higher emotional role functioning scores. Our study confirms substantial impairment of HRQoL in adults with SCD. HRQoL was mainly influenced by the recent occurrence of severe SCD complications. Our study suggests that a more effective treatment through a better compliance to HU therapy would provide benefit in terms of QoL.
Copyright (c) 2025 Giovanna Cannas, Solene Poutrel, Emilie Virot, Manon Marie, Alexandre Guilhem, Amal El-Kanouni, Richard Bourgeay, Marie-Grace Mutumwa, Mohamed Elhamri, Arnaud Hot http://creativecommons.org/licenses/by-nc/4.0
MOLECULAR MECHANISM OF TRAF6 IN MALIGNANT PROLIFERATION OF HUMAN NK/T CELL LYMPHOMA CELL HANK1
Background: Ubiquitination affects cancer progression by regulating both tumor-suppressing and tumor-promoting proteins in cancer. The current study sought to evaluate the role of TNF receptor associated factor 6 (TRAF6) in malignant proliferation of human NK/T cell lymphoma cell line HANK1. Methods: TRAF6 and MST1 expression levels in HANK1 cells were determined by RT-qPCR and Western blot analysis, followed by transfection of si-TRAF6 into HANK1 cells. Cell viability and proliferation were assessed by cell-counting kit-8 and 5-Ethynyl-2’-deoxyuridine (EdU) assays, and proliferating cell nuclear antigen (PCNA) expression levels in cells were determined by Western blot analysis. After that, cells were treated with MG132, followed by analysis of the binding of TRAF6 to macrophage stimulating 1 (MST1) via co-immunoprecipitation and the ubiquitination level of MST1 via the ubiquitination assay. The functional rescue experiment was performed with si-MST1 and si-TRAF6 in cells. Results: TRAF6 was upregulated in HANK1 cells. Inhibition of TRAF6 reduced cell viability and the number of EdU-positive cells, and downregulated PCNA expression. TRAF6 bound to MST1 to promote ubiquitination-meditated degradation of MST1. After MG132 treatment, the ubiquitination level of MST1 was declined. Silencing MST1 abolished the inhibition of TRAF6 on malignant proliferation of HANK1 cells. Conclusion: TRAF6 was upregulated in HANK1 cells and bound to MST1 to promote ubiquitination-meditated degradation of MST1, consequently facilitating malignant proliferation of HANK1 cells.
Copyright (c) 2025 Yan Qi, Chengbo Xu, Zesong Chen, Jiawei Chen, Congjie Chen http://creativecommons.org/licenses/by-nc/4.0
COULD PLASMA GLUCOSE (PG) INCREMENT (PG %) EXPAND THE CLINICAL WEIGHT OF OGTT? PRELIMINARY FINDINGS IN 19 TDT PATIENTS (Β-TDT) WITH NORMAL GLUCOSE TOLERANCE
Abstract. Background: Worldwide, glucose dysregulation (GD) and diabetes mellitus are common complications in transfusion-dependent β-thalassemia (β-TDT) patients. Impaired insulin sensitivity and insulin secretion are both involved in the deterioration of glucose tolerance from normal to a glucose-intolerant state. Objective: The main aim of the present study was to evaluate retrospectively the plasma glucose (PG) increment (PG %) at 2-h during oral glucose tolerance test (OGTT) over fasting plasma (FPG) concentration as a simple parameter to recognize early β -cell dysfunction in normoglycemic β-TDT patients with NGT and different severity of IOL. Patients and Methods: A total of 19 β-TDT young adult patients with normal OGTT were re-evaluated. OGTT was performed according to the American Diabetes Association (ADA) guidelines. Venous blood samples were collected at baseline and 30', 60' and 120' minutes to determine PG (mg/dL) and insulin concentrations (μIU/mL). The time required for the PG concentration to return to the fasting level was made by computing the percentage increment of 2-h PG in respect to FPG (PG%), using the formula [(2-h PG-FPG)/FPG]x 100. The early phase of insulin secretion (IGI) and sensitivity were assessed by validated surrogate indices calculated from parameters obtained during the four point OGTT. Results: The mean age of patients was 30.3 ± 5.7 (range:23.10-44.3). The mean ± SD, median and range of PG% increment, between 2 h-PG and FPG, was 35.5 ± 20.2 , 38.7 and 0 - 68.2, respectively. The PG% increment was negatively correlated to patient's age, FPG and IGI, and positively correlated with 2-h PG post-glucose load. IGI was negatively correlated with 1-h and 2-h PG after post-glucose load and positively correlated with oral disposition index (oDI). Conclusions: In conclusion the PG% is a simple useful screening parameter that can expand the clinical weight of OGTT and can provide valuable metabolic information on β-cell dysfunction.
Copyright (c) 2025 Vincenzo De Sanctis, Ashraf Soliman, Shahina Daar, Ploutarchos Tzoulis, Christos Kattamis http://creativecommons.org/licenses/by-nc/4.0
PLASMODIUM VIVAX INFECTIONS IN DUFFY-NEGATIVE INDIVIDUALS: A PARADIGM SHIFT IN INDIAN MALARIA EPIDEMIOLOGY
Aim: To investigate the occurrence of Plasmodium vivax infections in Duffy-negative individuals, challenging the long-held belief that P. vivax requires the Duffy antigen receptor for chemokines to infect human erythrocytes. Materials and Methods: In the present study, 365 samples were screened using serological techniques, PCR-RFLP analysis, and DNA sequencing of the ACKR1 gene promoter region mutation to identify Duffy-negative individuals. P. vivax infection was detected using PCR targeting the 18S rRNA gene and microscopic examination of Giemsa-stained blood smears. Results: Five individuals (1.36%) were confirmed Duffy-negative (Fy(a-b-)). Surprisingly, 3 out of these 5 Duffy-negative subjects (60%) were infected with P. vivax, as confirmed by both microscopy and PCR. Various parasite stages were observed in infected Duffy-negative samples, with parasitaemia ranging from 0.01% to 0.5%. Discussion: Our findings provide compelling evidence that P. vivax can infect Duffy-negative individuals, suggesting the existence of alternative invasion pathways or adaptations. This has profound implications for P. vivax biology, evolution, and global distribution. The burden of vivax malaria may be underestimated, particularly in regions with a high prevalence of Duffy negativity. This study highlights the need to reevaluate P. vivax epidemiology, diagnostic approaches, and control strategies, especially in areas previously considered at low risk. Further research is needed to elucidate the mechanisms enabling P. vivax invasion of Duffy-negative erythrocytes and to assess the clinical and epidemiological consequences of these infections.
Copyright (c) 2025 Roshan Shaikh, Ghosh Kanjaksha, Ajit Gorakshakar http://creativecommons.org/licenses/by-nc/4.0
ASSESSMENT OF THE EFFICACY OF PROCALCITONIN, C-REACTIVE PROTEIN AND ALBUMIN LEVELS-GUIDED ANTIBIOTICS USE IN SEPSIS
Background: Efficient management of sepsis requires precise antibiotic therapy. This study examines the efficacy of guiding such therapy using Procalcitonin (PCT), C-Reactive Protein (CRP), and albumin levels. Methods: A total of 127 adult sepsis patients were assigned to either standard care or a biomarker-guided group where antibiotic use was adjusted based on biomarker levels. Results: The biomarker-guided approach significantly reduced the duration of antibiotic therapy (9.0 vs. 10.5 days, P=0.04) and expedited antibiotic de-escalation. Hospital costs were lower in the biomarker-guided group (20,000 vs. 24,000 CNY, P=0.04), though reductions in secondary infections did not reach statistical significance. There was no significant difference in 28-day mortality rates. Conclusion: Biomarker-guided antibiotic therapy can enhance the efficiency of treatment in sepsis, reducing both duration and cost without impacting patient safety. These findings suggest the potential benefits of incorporating biomarkers into standard sepsis management protocols.
Copyright (c) 2025 Junyue Cao, YuChao Sun http://creativecommons.org/licenses/by-nc/4.0
EFFICACY OF VENETOCLAX COMBINED WITH AZACITIDINE IN ELDERLY PATIENTS WITH RELAPSED ACUTE MYELOID LEUKEMIA
Background: Elderly patients with relapsed acute myeloid leukemia (AML) have limited treatment options and poor prognosis. Venetoclax combined with azacitidine has shown promising activity in newly diagnosed or relapsed/refractory AML, but real-world data on older populations remain scarce. This study aimed to evaluate the efficacy, safety, and prognostic factors—including select blood biomarkers—of venetoclax plus azacitidine in elderly patients with relapsed AML. Methods: We conducted a single-center retrospective review of patients aged ≥65 years diagnosed with relapsed AML who received venetoclax plus azacitidine between January 2018 and December 2022. Patient demographics, baseline disease characteristics, and treatment details were collected. Blood biomarkers, such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and selected molecular markers (including FLT3-ITD and NPM1 mutations), were also assessed at baseline to evaluate their prognostic value. The primary endpoint was the overall response rate (ORR), defined as the sum of complete remission (CR) and CR with incomplete hematologic recovery (CRi). Secondary endpoints included overall survival (OS), event-free survival (EFS), and safety. Prognostic factors were identified through univariate and multivariate analyses using Cox proportional hazards models. Survival curves were constructed via the Kaplan-Meier method. Results: A total of 50 patients (median age, 72 years; range, 65–82) met the inclusion criteria. The ORR was 60% (40% CR and 20% CRi). The median OS was 9.2 months (95% CI: 6.8–11.5), and the median EFS was 6.0 months (95% CI: 4.2–8.3). Common Grade 3–4 adverse events included neutropenia (46%) and thrombocytopenia (32%). The 30-day treatment-related mortality rate was 4%. Elevated baseline LDH (≥ the upper limit of normal) was associated with reduced OS (p=0.03). Patients with high CRP levels and/or adverse molecular markers (e.g., FLT3-ITD positivity) also showed a trend toward poorer survival, although these did not reach statistical significance in the multivariate model. Multivariate analysis confirmed poor Eastern Cooperative Oncology Group (ECOG) performance status and adverse cytogenetics as independent predictors of reduced OS. Conclusion: Venetoclax combined with azacitidine demonstrated encouraging efficacy and manageable toxicity in this retrospective analysis of elderly patients with relapsed AML. Elevated LDH and adverse molecular/cytogenetic profiles were associated with worse outcomes. These findings highlight the importance of integrating blood biomarker assessment into routine evaluation and suggest venetoclax-based regimens may be a viable therapeutic option in older, relapsed AML populations. Prospective multicenter studies are warranted to confirm these results and refine patient selection.
Copyright (c) 2025 Linjuan Xu http://creativecommons.org/licenses/by-nc/4.0
EVOLVING DISEASE SPECTRUM AND CHARACTERISTICS OF PEOPLE WITH HIV IN EASTERN CHINA: A 12-YEAR STUDY
Background Acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) remains a serious public health problem. Opportunistic infections, and malignancies are the more frequent cause of hospitalization. We investigated hospitalized people with HIV (PWH) over the past 12 years, to determine the type and changing trends of the disease presentation in a large reference academic centre in Eastern China. Methods We evaluated a total of 2,140 hospitalized PWH from January 2010 to December 2021. Demographic, clinical and laboratory data, opportunistic infections, malignancies and in-hospital outcomes were collected and analyzed. Results Over time, the incidence of opportunistic infections has declined. Conversely, the incidence of malignancies has increased, and non-AIDS-defining cancers (NADCs) have occurred more frequently than ADCs. In 2020-2021, the incidence of NADCs became higher than that of opportunistic infections. The overall in-hospital mortality rate was 8.1%. and the in-hospital mortality gradually decreased over time. Opportunistic infections, malignancies, and CD4+T cell count were independent predictors for in-hospital mortality. Conclusion Our study provided a comprehensive description of the disease characteristics of PWH in eastern China over the past 12 years. The disease spectrum of PWH has undergone tremendous changes over time, highlighting the necessity of early HIV diagnosis and providing greater access to optimal treatment and management strategies. Keywords: HIV; Early Diagnosis; Changing treatments.
Copyright (c) 2025 Ye Xiong, Bohao Dai, Dairong Xiang, Jean-Pierre Routy, Biao Zhu http://creativecommons.org/licenses/by-nc/4.0
INTEGRATION OF CD200, CD43 AND ROR1 IN MULTIPARAMETER FLOW CYTOMETRY (MFC) ROUTINE PANELS FOR THE DIFFERENTIAL DIAGNOSIS OF B-CELL LYMPHOPROLIFERATIVE DISORDERS (B-LPDS)
Background: Clonal mature B-cell lymphoproliferative disorders (B-LPDs) are a heterogeneous group of neoplasia characterized by the proliferation of mature B lymphocytes in the peripheral blood, bone marrow and/or lymphoid tissues. B-LPDs classification into different subtypes and their diagnosis are based on a multiparametric approach, however accurate diagnosis may be challenging, especially for cases of ambiguous interpretation. Multiparameter flow cytometry (MFC) represents an extensively used technique to detect the presence of different cellular lines in immunology and hematology. MFC results provide an essential contribution to B-LPDs diagnostic process, even more considering that panels are constantly integrating novel markers to improve diagnostic accuracy. Objectives: The aim was to evaluate the contributing role of MFC routinary studies analyzing the expression and the mean fluorescence intensity (MFI) of CD200, ROR1 and CD43 in various B-LPDs, to evaluate their usefulness in differential diagnosis of these diseases. Methods: We retrospectively evaluated a total of 2615 consecutive cases of newly samples (collected mostly from patients with lymphocytosis) analyzed by MFC carried out in B-LPDs diagnostic process referred to the Division of Hematology of ‘Sapienza’ University of Rome. We compared results of CD200, ROR1 and CD43 expression percentage and their MFI between different subtypes of B-LPDs. Results: In chronic lymphocytic leukemia (CLL) CD200, ROR1 and CD43 were always expressed with bright intensity. CLL samples presented CD200 expression and MFI [CD200%, mean: 100 (range, 24-100); positivity rate: 100%; MFI, mean = 168 (range, 10-1200)] and highly expressed statistically higher than mantle cell lymphoma (MCL) (p<0.001), which is usually negative for CD200, and variant hairy cell leukemia (vHCL, according to 2022 ICC) (p<0.001), but comparable with classic HCL (cHCL) (p>0.9). ROR1 resulted expressed in all CLL [ROR1%, mean: 100 (range, 52-100), positivity rate: 100%; MFI, mean 53 (range, 10-202)] and MCL cases with comparable MFI (p>0.9). CD43 expression and MFI were significantly higher in CLL [CD43%, mean: 99 (range, 59-100); positivity rate: 100%; MFI, mean = 218 (range, 41-980)] than in MCL, vHCL, cHCL and all the others mature B-cell neoplasia (p<0.001). CD200 and CD43 expression and MFI were significantly higher in cHCL compared to vHCL. Among the others mature B-cell neoplasia, CD200 was variably expressed in follicular lymphoma (FL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL) and lymphoplasmacytic lymphoma (LPL). ROR1 and CD43 presented a very low expression percentage in this latter group, being mostly negative. Persistent polyclonal B-cell lymphocytosis (PPBL) resulted uniformly positive for CD200 and negative for ROR1 and CD43. Conclusions: Our data suggest that evaluation of CD200, ROR1 and CD43 antigens and their intensity of expression, along with commonly used markers in MFC routine panels for B-LPDs, might be extremely useful for a prompt diagnostic evaluation in the differential diagnosis of these diseases.
Copyright (c) 2024 Alessandro Laganà, Raffaele Maglione, Alessandro Costa, Biancamaria Mandelli, Maria Laura Bisegna, Maria Laura Milani, Valeria Filipponi, Maria Grazia Nardacci, Tania Soriano, Eugenio Santacroce, Luigi Petrucci, Carla Giordano, Maurizio Martelli, Maria Stefania De Propris http://creativecommons.org/licenses/by-nc/4.0
IMPACT OF RED CELL EXCHANGE TRANSFUSION ON INFLAMMATORY MARKERS IN SICKLE CELL DISEASE
Background: Red Blood Cell Exchange (RBCX) is a common treatment for pediatric sickle cell disease (SCD), particularly in cases complicated by cerebrovascular disease. Since inflammation plays a crucial role in SCD and elevated pro-inflammatory cytokines are observed in these patients, this study hypothesized that RBCX might lower these cytokines and aimed to assess the impact of this technique on these markers. Methods: This prospective and observational study included pediatric SCD patients (HbSS genotype) enrolled in a chronic RBCX program at a Portuguese Hospital from October 2022 to May 2024. Patients with acute exacerbations were excluded. Blood samples were collected before and after RBCX to assess hematological parameters and inflammatory cytokines. Data were analyzed using SPSSv25Ⓡ (Significance level set at p < 0.05); Informed consents were obtained. Results: Thirty-one children (median age 10 years) were studied. Fourteen patients were new to RBCX, while 17 were already in a chronic RBCX program. RBCX mainly aimed to prevent cerebrovascular disease (81%). A total of 286 RBCXs were analyzed, showing no major adverse events or disease-related hospitalizations. Hemoglobin levels increased by 1.5g/dL, HbS decreased by 69%, and leukocytes decreased by 20%. IL-1, ferritin and procalcitonin showed high levels before RBCX. IL-1 levels dropped significantly post-RBCX (p<0.001), while other markers like C-Reactive Protein, IL-6, and TNF-α showed no significant changes. Conclusions: RBCX safely reduces HbS, leukocytes, and IL-1 levels, suggesting a modulatory effect on inflammation in SCD patients. Further research is needed to explore cytokine mechanisms in SCD.
Copyright (c) 2024 Adriana Costa, Inês Mendes, Joana Lage, Marta Moniz, Catarina Amorim, Pedro Nunes, Helena Almeida, Carlos Escobar, Ana Ventura, Teresa Ferreira http://creativecommons.org/licenses/by-nc/4.0
CAUSAL RELATIONSHIP BETWEEN HELICOBACTER PYLORI ANTIBODIES AND IMMUNE THROMBOCYTOPENIA: A MENDELIAN RANDOMIZATION STUDY
Background Previous observational studies have suggested a potential causal relationship between Helicobacter pylori (H. pylori) infection and Immune thrombocytopenia (ITP). However, the evidence for causal inference remains contentious, and the underlying mechanisms require further investigation. In order to delve deeper into the relationship between H. pylori and ITP, we conducted a Mendelian randomization (MR) analysis. Method In this study, we used two-sample Mendelian Randomization (MR) to assess the causality of seven different specific protein antibodies targeting H. pylori on ITP. 76 single nucleotide polymorphisms (SNPs) related to H. pylori antibodies levels were obtained from the European Bioinformatics Institute (EBI). Summary data of ITP was obtained from the FinnGen database, Inverse variance weighted (IVW) analysis was identified as our main method. To ensure the reliability of the findings, many sensitivity analyses were performed. Result Genetically predicted serum levels of H. pylori GroEL antibodies were positively associated with an increased risk of ITP (odds ratio [OR] = 1.802, 95% CI 1.106–2.936, P = 0.01799). No causal relationship was found between other H. pylori antibodies and ITP. Conclusion The outcomes derived from our two-sample Mendelian randomization analysis demonstrate a discernible link between the levels of H. pylori GroEL antibodies and an augmented susceptibility to ITP. However, it is imperative to expand the sample size further in order to corroborate the correlation between H. pylori infection and ITP.
Copyright (c) 2024 Yuzhan Chen, Qitian Mu, Guifang Ouyang http://creativecommons.org/licenses/by-nc/4.0
A MULTICENTER ICET-A SURVEY ON ADHERENCE TO ANNUAL ORAL GLUCOSE TOLERANCE TEST (OGTT) SCREENING IN TRANSFUSION-DEPENDENT THALASSEMIA (TDT) PATIENTS - THE EXPERT CLINICIANS’ OPINION ON FACTORS INFLUENCING THE ADHERENCE AND ON ALTERNATIVE STRATEGIES FOR ADHERENCE OPTIMIZATION
Abstract. Background: Current guidelines for screening glucose dysregulation (GD) in patients with transfusion-dependent thalassemia (TDT) recommend an annual 2-hour oral glucose tolerance test (OGTT) starting at the age of 10 years. Objective: Assessment of adherence to OGTT screening in patients with TDT. Methods: A questionnaire was distributed to 18 Thalassemia Centers in 10 different countries, targeting factors influencing adherence to annual OGTT screening in specialized multidisciplinary pediatric and adult TDT units and identifying strategies to improve adherence to OGTT in TDT patients. Results: The mean reported percentage of all types of GD across 16 of the 18 centers ,at last OGTT assessment, was 32.0% while the mean percentage for thalassemia-related diabetes mellitus (Th-RDM) was 12.2 ± 9.7% (range: 0% - 41%; median:13.2 % ) in all participating centers. Notably, a high percentage of suboptimal or poor adherence to annual OGTT screening (mean 41.3%; range 10-90%) was reported by 17/18 centers. Poor adherence to annual OGTT among eligible patients was multifactorial, related to both patient-, and healthcare system barriers. The most commonly suggested actions by hematologists and endocrinologists for improving the adherence to OGTT were: flexibility in timing, easy approach to test location, improved collaboration among team members and persistent reminding. Conclusions: Young adult patients with TDT are at high risk for developing GD and Th-RDM, thus annual screening with a 2-hour OGTT is recommended. Nevertheless, there are several patient barriers associated with low adherence to annual OGTT. It is desirable to develop intensive initiatives to improve screening rate for GD, while studies are warranted to update the current guidelines in TDT patients with low risk factors for GD and for countries with low-resource settings.
Copyright (c) 2024 Vincenzo De Sanctis http://creativecommons.org/licenses/by-nc/4.0
ATYPICAL DERMATOLOGICAL MANIFESTATIONS OF SYPHILIS IN ADVANCED HIV: A CASE-BASED NARRATIVE REVIEW
Syphilis, a sexually transmitted infection caused by Treponema pallidum (T. pallidum), is re-emerging globally. Recent epidemiological data show a rising incidence, particularly among men who have sex with men (MSM). Known as ‘the great mimic’ for its broad clinical spectrum, secondary syphilis classically presents with a maculopapular rash involving the trunk and extremities. However, it can also present with atypical cutaneous manifestations, especially in immunocompromised patients. This aspect may contribute to delayed diagnosis and treatment. Starting from a clinical case, we will conduct a literature review on syphilis/HIV coinfection, with a particular focus on the broad spectrum of cutaneous manifestations and the key differential diagnoses involved. We report the case of a 60-year-old male living with HIV who presented with non-pruritic, polymorphic skin lesions sparing the palms and soles. The patient had a prior history of treated latent syphilis. Initial diagnostic workup excluded common differentials, including monkeypox and fungal infections. Serologic testing confirmed active syphilis with a reactive Rapid Plasma Reagin (RPR) titer of 1:32, skin biopsy showed dense plasma cell-rich infiltrate, and immunohistochemistry was positive for T. pallidum. Despite negative cerebrospinal fluid findings, neurological symptoms prompted treatment with intravenous penicillin G, and the symptoms resolved with treatment. This case underscores the importance of considering syphilis in the differential diagnosis of atypical dermatologic presentations, given its increasing prevalence and potential for severe systemic involvement.
Copyright (c) 2025 Irene Scarvaglieri, Federico Cesanelli, Giorgio Tiecco, Iacopo Ghini, Davide Minisci, Caterina Davoli, Stefano Rapino, Emanuele Focà, Maria Alberti, Martina Salvi, Francesco Castelli, Eugenia Quiros-Roldan http://creativecommons.org/licenses/by-nc/4.0
BRUTON’S TYROSINE KINASE (BTK) MUTATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A CLINICAL VIEW.
Bruton’s tyrosine kinase inhibitors (BTKis) have reshaped the management of chronic lymphocytic leukemia (CLL). The first-generation BTKi ibrutinib demonstrated significant efficacy, leading to the development of second-generation agents (acalabrutinib, zanubrutinib) with improved selectivity and safety. However, resistance—most often driven by BTK C481S mutations—remains a major therapeutic limitation. Non-covalent BTKis, such as pirtobrutinib, offer effective options for patients relapsing after covalent BTKi therapy. However, the emergence of novel resistance mutations continues to limit durable responses. As insights into the molecular basis of BTK resistance evolve, routine mutation testing is poised to become integral to personalized treatment in CLL. Future clinical trials are expected to adopt mutation-driven stratification to guide therapeutic sequencing. Ultimately, overcoming BTKi resistance will require innovative strategies, including BTK degraders, bispecific antibodies, and T cell–engaging immunotherapies.
Copyright (c) 2025 Stefano Molica http://creativecommons.org/licenses/by-nc/4.0
MANAGING INVASIVE FUNGAL INFECTIONS DURING ALLOGENEIC HEMATOPOIETIC TRANSPLANTATION: A 2025 UPDATE
Invasive fungal infections (IFIs) mostly affect immunocompromised hosts and are responsible for high rates of complications and mortality. Prevalence of IFIs has been reported between 7 and 15% and is evolving due to the introduction of new drugs in the prophylaxis of high-risk patients. Invasive candidiasis has become less frequent, while cases of aspergillosis are increasing. The most important risk factors for IFIs can be divided into 3 categories: those related to the hematological neoplasm, those related to the patient's lifestyle, and those dictated by the transplant characteristics. In high-risk patients, prophylaxis is driven by both local epidemiology and time of the engraftment. In the pre-engraftment period there is a wide spectrum of drugs that could be chosen as antifungal, while in the post-engraftment period posaconazole is recommended for patients presenting GvHD undergoing immunosuppression. Regarding treatment, voriconazole is still the recommended drug for invasive aspergillosis, although adverse events, toxicity, and drug interactions are particularly relevant. In the management of IFIs, international guidelines recommend the best drugs for prophylaxis and treatment, but the future holds new molecules that are already demonstrating excellent efficacy and tolerability.
Copyright (c) 2025 Martina Quattrone, Alessia Di Pilla, Sara Brunetti, Antonio Giordano, Luana Fianchi, Livio Pagano, Marianna Criscuolo http://creativecommons.org/licenses/by-nc/4.0
Guest Editor: Pellegrino Musto HOW FIRST-LINE THERAPY IS CHANGING IN NON-TRANSPLANT ELIGIBLE MULTIPLE MYELOMA PATIENTS.
Treatment outcomes for patients with multiple myeloma have improved in recent decades thanks to new insights into the biology of the disease and the introduction of new drugs and therapeutic approaches. More than half of patients with multiple myeloma are not eligible for transplantation and for years their treatment has been difficult due to the heterogeneity of this patient group and the lack of treatment options. Recently, attention has focused on the concept of frailty and its quantification in order to adapt the schedule and dosage of treatment to the state of fitness. Modulation of therapy for frailty can reduce side effects and toxicity-related death and define the various successes of therapy. The role of frailty and the development of new tools may provide a way forward to customize the treatment of different patients with multiple myeloma who are not eligible for transplantation. The use of the new association, particularly based on monoclonal antibodies against CD38, showed profound and durable results in terms of progression-free survival and overall survival. Today, these combinations, especially daratumumab-lenalidomide and dexamethasone, represent the “gold standard” of treatment for these patients. The latest quadruplet therapies and cell-directed therapies, including bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) treatment, appear to be very effective and achieve a high rate of negative minimal residual disease. These latter approaches could redefine the population over the age of 65 that is now considered transplant eligible.
Copyright (c) 2025 Daniele Derudas http://creativecommons.org/licenses/by-nc/4.0
OUTLINE OF IRON METABOLISM, WITH EMPHASIS TO ERYTHROID CELLS
Iron is required for several vital biological processes in all human cells. In mammals, a considerable number of proteins are involved in iron metabolism and utilize iron in many essential cellular processes, such as oxygen transport, mitochondrial respiration, gene regulation and DNA synthesis or repair. Iron metabolism is a complex system finely regulated at both systemic and cellular levels. It involves the development of specialized mechanisms for iron absorption, transport, recycling, storage and export, and protection against toxic compounds that can be generated during iron redox cycling in the presence of oxygen. The erythropoietic compartment consumes the majority of iron to support the high demand for hemoglobin synthesis. A tightly regulated system enables efficient iron uptake by erythroid cells and its subsequent processing for the synthesis of large amounts of heme, which is then incorporated into hemoglobin. A bidirectional regulatory system between erythropoiesis and iron metabolism ensures precise coordination between the two processes. This regulation is often disrupted in various anemic conditions. Keywords : Iron; Ferritin; Ferroportin; DMT1; Hepcidin
Copyright (c) 2025 Ugo Testa, Elvira Pelosi, Germana Castelli http://creativecommons.org/licenses/by-nc/4.0
FROM LEGACY TO INNOVATION: PIDOTIMOD’S EXPANDING THERAPEUTIC HORIZON
Pidotimod, a synthetic dipeptide, has been utilized for over three decades as an immunomodulatory agent to prevent recurrent respiratory infections, particularly in immunocompromised populations such as children and the elderly. Originally developed for its ability to enhance innate and adaptive immune responses, pidotimod is now being revisited in light of new clinical insights and emerging therapeutic needs. Recent studies have expanded its potential beyond traditional indications, with evidence supporting its role in patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), allergic rhinitis, and even viral infections, including SARS-CoV-2. Pidotimod exerts its effects by stimulating dendritic cells, enhancing toll-like receptor (TLR) expression, and promoting cytokine production, including IL-2 and IFN-γ, thereby supporting both cellular and humoral immunity. This broad-spectrum immune modulation makes pidotimod a promising adjunct in managing immune-mediated diseases and infections in both immunocompetent and immunocompromised individuals. In this review, we examine pidotimod's pharmacodynamics, summarize clinical evidence from recent studies, and explore its evolving role in modern therapeutic strategies for infectious diseases. Given its safety profile and oral administration, pidotimod holds significant promise not only for preventing infections but also as part of a broader immunomodulatory approach in complex disease management.
Copyright (c) 2025 Claudio Ucciferri, Francesca Chiappini, Jacopo Vecchiet, Katia Falasca http://creativecommons.org/licenses/by-nc/4.0
WALDENSTRÖM MACROGLOBULINEMIA - A STATE-OF-THE-ART REVIEW: PART 2- FOCUS ON THERAPY
Abstract: The diagnosis and treatment of Waldenstrom macroglobulinemia (WM) are the subjects of this two-part review, which aims to provide current and thorough knowledge of these topics. The first portion of the study, previously published, investigated the epidemiology, etiology, clinicopathological aspects, differential diagnosis, prognostic factors, and impact on WM-specific groups. Specifically, this second section examines both the standard consolidated method and the new therapeutic strategy to handle the complex topic of the treatment of WM.
Copyright (c) 2025 Michele Bibas, Shayna Sarosiek , jorge castillo http://creativecommons.org/licenses/by-nc/4.0
Guest Editor: Pellegrino Musto BISPECIFIC ANTIBODIES AND CAR T IN MULTIPLE MYELOMA: APPROPRIATE SELECTION OF PATIENTS AND SEQUENCING
T-cell redirecting therapies (TCR) marked a step forward in the treatment of relapsed/refractory multiple myeloma (RRMM). These agents, represented by chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsAbs), proved to ameliorate the prognosis of difficult-to-treat patients in pivotal clinical trials, leading to their introduction into clinical practice. Both strategies rely on recruiting patients’ T-cells against specific tumor antigens, with B-cell maturation antigen (BCMA) and G-protein coupled receptor group C family 5 member D (GPRC5D) being the targets most extensively studied. Nevertheless, most of these regimens under the current label do not hesitate in a clear plateau of survival curves, thus raising the scenario of patients receiving more than one TCR agent in sequence. Also, they differ in their toxicity profiles and administration features. Consequently, the appropriate application of these agents mandates a careful selection of the right treatment for the right patient, with the ultimate intent of optimizing patient outcomes. In this respect, practical considerations regarding tumor- and patient-specific features are of high importance. Tailored clinical trials and analysis of real-word experiences are also crucial to produce evidence-based recommendations. Likewise, pre-clinical research is critical for the conceptualization of treatment algorithms potentially driven by immunological clues and knowledge of mechanisms of resistance. In this review we aim at providing practical guidance for defining the most appropriate treatment sequencing and determining the selection of patients for each treatment.
Copyright (c) 2025 Michele Puppi, Ilaria Sacchetti, Katia Mancuso, Paola Tacchetti, Lucia Pantani, ilaria Rizzello, Miriam Iezza, Marco Talarico, Enrica Manzato, Simone Masci, Roberta Restuccia, Simona Barbato, Silvia Armuzzi, Barbara Taurisano, Ilaria Vigliotta, Elena Zamagni http://creativecommons.org/licenses/by-nc/4.0
TOXICITIES ASSOCIATED WITH CAR-T CELL THERAPIES
Chimeric antigen receptor (CAR) T-cells therapy has improved the outcomes of patients with relapsed/refractory B-cell lymphomas, B-cell acute lymphoblastic leukemia and multiple myeloma. However, CAR-T cell therapy is also associated with distinct toxicities that contribute to morbidity and mortality. A large number of studies now define the different toxicities associated with CAR-T cell therapy and have, in part, clarified their mechanisms. In particular, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two main acute toxicity events that occur after CAR-T cell infusion. Other CAR-T-related toxicities occur later after CAR-T cell infusion and include B-cell aplasia, hypogammaglobulinemia, infections and cytopenia. Infections represent the main cause of non-relapse death observed in patients undergoing CAR-T cell therapy. Second primary malignancies are rare and are mainly represented by myeloid malignancies.
Copyright (c) 2025 Ugo Testa, Dr. Germana Castelli, Dr. Elvira Pelosi, Dr. Galli, Prof. Patrizia Chiusolo http://creativecommons.org/licenses/by-nc/4.0
Guest Edtor: Pellegrino Musto NOVELTIES ON MULTIPLE MYELOMA FROM THE MAIN 2024 HEMATOLOGY CONFERENCES
Despite the introduction of several therapies in recent years, multiple myeloma (MM) remains a difficult to treat haematological malignancy due to its extreme inter- and intra-patient heterogeneity. However, at the 2024 major international conferences, very significant data have emerged on new approaches that can improve outcomes even in high-risk or very advanced disease. Up-front quadruplet combinations including anti-CD38 monoclonal antibodies proved to be the best therapy in terms of depth of response and long-term efficacy in both transplant eligible and not eligible patients with MRD assessment that could play a key role in determining the duration of therapy avoiding unnecessary overtreatment. However, also quadruplets fail to overcome negative prognostic value of high risk cytogenetics or circulating tumor cells therefore in patients with these features alternative approaches will have to be evaluated. Moreover, considering that not all patients, particularly older and frail ones, will be able to undergo such therapies, it will be necessary to refine the ability to identify the most appropriate therapy for each patient. Bispecific antibodies and CAR-T cells represent the new frontier in the treatment of advanced MM but they have shown even more efficacy with less toxicity in early relapses and in functional high-risk patients. Extremely promising are the results obtained with the inclusion of novel immunotherapies in the upfront setting. In relapsed/refractory MM patients agents as belantamab mafodotin and CELMoDs, in combination with proteasome inhibitors or immunomodulatory agents, will probably represent another valid option.
Copyright (c) 2025 Sonia Morè, Laura Corvatta, Valentina Maria Manieri, Erika Morsia, Antonella Poloni, Massimo Offidani http://creativecommons.org/licenses/by-nc/4.0
CUPROPTOSIS: A REVIEW ON MECHANISMS, ROLE IN SOLID AND HEMATOLOGICAL TUMORS, AND ASSOCIATION WITH VIRAL INFECTIONS
Cuproptosis is a distinct modality of regulated cell death precipitated by an overload of intracellular copper, critically dependent on mitochondrial respiration. The underlying mechanism involves the direct interaction of copper ions with lipoylated components integral to the mitochondrial tricarboxylic acid (TCA) cycle. This binding event triggers the aggregation of these proteins, induces significant proteotoxic stress, and leads to the depletion of essential iron-sulfur cluster proteins, culminating in cell demise. Given that copper homeostasis is frequently dysregulated within cancer cells, rendering them potentially more susceptible to copper-induced toxicity, cuproptosis has rapidly become a focal point of oncological research. This systematic review meticulously analyzes and synthesizes findings from a curated collection of 45 research articles. It aims to provide a comprehensive description of the molecular intricacies of cuproptosis, explore its documented associations with a spectrum of solid tumors (including gastric, lung, liver, neuroblastoma, and ovarian cancers) and lymphoma, and examine its emerging connections with viral infections like COVID-19 and pseudorabies virus. The review elaborates on the reported prognostic significance of cuproptosis-related genes and associated pathways across various malignancies. Furthermore, it details the burgeoning therapeutic strategies designed to harness cuproptosis, encompassing the application of copper ionophores, the development of sophisticated nanomedicine platforms, and synergistic approaches that combine cuproptosis induction with immunotherapy, chemotherapy, or sonodynamic therapy. The potential clinical utility of cuproptosis-associated biomarkers for predicting patient prognosis and therapeutic response is discussed based on the evidence presented in the reviewed literature.
Copyright (c) 2025 MAURIZIO MARTINI, Pietro Tralongo, Mariagiovanna Ballato, Vincenzo Fiorentino, Walter Giordano, Valeria zuccalà, Cristina Pizzimenti, Arianna Bakacs, Antonio Ieni, Giovanni Tuccari, Guido Fadda, Luigi Maria Larocca http://creativecommons.org/licenses/by-nc/4.0
HEPARIN-BINDING PROTEIN AS A DIAGNOSTIC AND PROGNOSTIC MARKER OF INFECTIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Heparin-binding protein (HBP) is a granule protein derived from neutrophils, located in secretory vesicles and neutrophilic granules, also known as cationic antimicrobial protein of 37 kDa (CAP37) or azurocidin. This study evaluates the diagnostic and prognostic value of HBP levels in relation to infection, organ dysfunction, and mortality in adult patients. A systematic review and meta-analysis were conducted by searching PubMed, Web of Science, EMBASE, and the Cochrane Database from their inception through June 2024. Original studies assessing HBP levels' diagnostic and prognostic utility in predicting infection and disease severity in critically ill adult patients were included. The primary outcome was the diagnostic and predictive role of HBP in infection and severity. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to evaluate bias risk. A total of 56 studies involving 11,486 patients were included. Pooled analysis showed HBP had a sensitivity of 0.87 (95% CI, 0.82–0.91), specificity of 0.87 (95% CI, 0.79–0.92), and an AUC of 0.93 (95% CI, 0.91–0.95) for infection diagnosis. For prognostic assessment, sensitivity was 0.77 (95% CI, 0.74–0.80), specificity was 0.72 (95% CI, 0.68–0.76), and AUC was 0.81 (95% CI, 0.78–0.85). HBP outperformed procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count (WBC) in diagnosing and predicting critical illness. No publication bias was detected. HBP demonstrates high sensitivity and specificity for diagnosing infections in critically ill adult patients. Additionally, it effectively predicts disease progression, including organ dysfunction and mortality, surpassing traditional biomarkers such as PCT, CRP, and WBC. All that cannot be true for subjects with severe neutropenia. Keywords: Heparin-binding protein; Systematic review, Meta-analysis, Diagnosis, Prognosis, Infectious disease, Sepsis, Organ failure, Mortality.
Copyright (c) 2025 Wenshan Yang, Wei Dong http://creativecommons.org/licenses/by-nc/4.0
Guest Editor: Pellegrino Musto AN UPDATE OF THE APPROPRIATE SEQUENCING FOR SALVAGE THERAPIES IN MULTIPLE MYELOMA
Current treatment strategies have led to unpredictable improvements in the management of multiple myeloma (MM) over time. However, resistance to therapy, particularly regarding lenalidomide refractoriness and, more recently, daratumumab and lenalidomide refractoriness, even in the first line setting, has become an increasingly significant issue in recent years. This complicates the identification of the optimal treatment algorithm for patients with relapsed/refractory MM, particularly at first relapse. In this review, we focus on current strategies for MM patients progressing on or after lenalidomide-based and daratumumab-lenalidomide-based regimens. The forthcoming availability of next-generation immunotherapies, along with a deeper understanding of resistance mechanisms, is highly anticipated. Meanwhile, based on promising results from recent studies, the approval of novel drugs to expand the current therapeutic armamentarium against MM is bringing us closer to the goal of making a potential cure for the disease much more achievable in the hopefully near future.
Copyright (c) 2025 Gregorio Barila', Francesca Rezzonico, Laura Pavan, Alessandro Corso, Renato Zambell0 http://creativecommons.org/licenses/by-nc/4.0
PLASMA CELL LEUKEMIA UPDATE ON IMMUNOPHENOTYPE, MOLECULAR CHARACTERISTICS, AND THERAPY. The second part of plasma cell neoplasms with spreading in the blood and tissues
Plasma cell leukemia (PCL) is a rare and aggressive form of multiple myeloma (MM), characterized by the presence of malignant plasma cells in the peripheral blood. Until 2021, PCL was defined by having plasmacytosis making up at least 20% of the differential white blood cell count . PCL was found in 2-4% of newly diagnosed MM cases (primary PCL). It can also develop from a preexisting, usually end-stage, MM, known as secondary PCL (sPCL), which exhibits distinct biological and clinical features. Both primary plasma cell leukemia (pPCL) and secondary plasma cell leukemia (sPCL) are very rare presentations of MM. However, the rate of MM transforming into sPCL is increasing as patients are living longer. According to the International Myeloma Working Group, plasma cell leukemia is generally diagnosed when the percentage of CPCs in peripheral blood exceeds 5%. PCL has a more aggressive clinical presentation than MM, involving more severe cytopenia, hypercalcemia, and renal failure. Higher tumor burden and proliferation activity in PCL are reflected by elevated levels of B2-microglobulin and lactate dehydrogenase (LDH). Extramedullary localization at diagnosis is more common in pPCL and sPCL than in MM. Conversely, osteolytic lesions are less frequent in pPCL. The immunophenotype of PCL expresses the common MM markers, CD38 and CD138. Still, it exhibits a more immature phenotype than MM. Molecularly, PCL lacks a specific marker but shows a markedly lower frequency of hyperploidy, gains of chromosome 1, and translocations t(14;16) or t(14;20). The recent therapy of PCL is similar to that of other high-grade myelomas, taking advantage of anti-proteasome, like bortezomib, an immunomodulator, like lenalidomide, and dexamethasone triplet + anti-CD38 antibody and/or cyclophosphamide, and hematopoietic stem cell transplantation. However, the results are not as good as in the other forms of myeloma.
Copyright (c) 2025 Giuseppe G.M. Leone, Ugo Testa http://creativecommons.org/licenses/by-nc/4.0
Guest Editor: Pellegrino Musto HOW FIRST LINE THERAPY IS CHANGING IN TRANSPLANT-ELIGIBLE MULTIPLE MYELOMA PATIENTS
Multiple myeloma is a malignant haematological neoplasm characterized by the proliferation of plasma cells in the bone marrow. Each year, over 35,000 new cases are diagnosed in the United States, and nearly 13,000 patients die from the disease1. The main cause of morbidity is bone disease, characterized by osteolytic lesions, which, unlike other malignancies that metastasize to bone, are not followed by new bone formation2. Other major clinical manifestations include anemia, hypercalcemia, renal failure, and an increased risk of infections. Approximately 1-2% of patients present with extramedullary disease (EMD) at the time of diagnosis, while 8% develop EMD later in the course of the disease3. Although multiple myeloma remains incurable, its treatment continues to evolve rapidly. Approved therapies include immunomodulatory agents (IMiDs, such as thalidomide, lenalidomide, and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), and monoclonal antibodies (mAb) targeting CD38 (especially daratumumab and isatuximab) and SLAMF7. New therapeutic avenues include bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) therapy4-5. The latest ESMO (European Society for Medical Oncology)6 and NCCN (National Comprehensive Cancer Network) guidelines7 have set the standard of care for patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation, particularly those in good general condition and < 70 years old. This approach is divided in four phases: induction therapy, hematopoietic stem cell collection and autologous transplant, consolidation, and maintenance. The most significant differences between the guidelines occur during the induction phase, influenced by regulatory approvals in the United States and Europe. This article will focus on the changing landscape of therapies for newly diagnosed multiple myeloma (NDMM) in transplant-eligible (TE) patients and how the trend is increasingly focusing on therapies targeting minimal residual disease (MRD) and baseline risk stratification.
Copyright (c) 2025 Yasmine Houbaida, Maria Livia Del Giudice, Sara Galimberti, Gabriele Buda http://creativecommons.org/licenses/by-nc/4.0
Guest Editor: Pellegrino Musto REFINING HIGH-RISK MULTIPLE MYELOMA: ADVANCEMENTS IN GENOMIC, CLINICAL, AND PROGNOSTIC CRITERIA
Multiple myeloma (MM) is a heterogeneous disease with MM patients experiencing different clinical outcomes depending on the disease’s biological features. Novel insights into the molecular mechanisms of MM have led to the introduction of sophisticated drugs, which dramatically improved patient treatment and survival. To date, young patients with newly diagnosed MM could experience a median overall survival (OS) of 10 years. Nevertheless, a small proportion of patients still undergoes early disease progression and death. Indeed, cases defined as ultra-high-risk MM (uHRMM) and high-risk MM (HRMM) are destined for a worse outcome, with an OS of 2-3 and 3-5 years, respectively. In this regard, current risk stratification systems failed to identify this subset of patients better. The application of existing risk models has led to the identification of extremely heterogeneous categories of patients, and they have not taken into account biological and clinical differences. The concept of HRMM was initially formalized in 2015. Since then, a great effort has been made to identify those parameters whose presence pone MM patients at higher risk of developing an early relapse. The simultaneous presence of 2 or more unfavorable cytogenetic abnormalities, the identification of an extramedullary disease or the detection of circulating plasma cells, as well as high-risk gene expression profiling (GEP) signature, have shown to be well related to a worse outcome and are going to be incorporated into new prognostic systems. The introduction of the Individualized Risk Model for Multiple Myeloma (IRMMa) marks a significant advancement in the management of HRMM by integrating genomic and clinical data to tailor treatment strategies. This model demonstrates improved prognostic accuracy compared to traditional staging systems and emphasizes the importance of personalized treatment approaches. The implementation of these advanced tools is essential for enhancing precision medicine in MM and improving outcomes for patients in high-risk categories.
Copyright (c) 2024 Dr. Enrica A. Martino, Dr. G. Mele, Dr. F. Morabito, Massimo Gentile http://creativecommons.org/licenses/by-nc/4.0
PLASMACELL NEOPLASMS WITH SPREADING IN THE BLOOD AND TISSUES: EXTRAMEDULLARY MYELOMA DISEASE A RARE AGGRESSIVE FORM OF MULTIPLE MYELOMA (First of two parts)
Multiple myeloma is a disease related to the proliferation of malignant plasma cells; in the large majority of patients the disease is confined at the level of bone marrow. However, in a minority of patients the malignant plasma cells are localized also outside bone marrow, either at the level of peripheral blood (plasma cell leukemia) or at the level of soft tissues (extramedullary multiple myeloma). These two rare forms of aggressive MM (ultrahigh-risk (uHR) MM as MM leading to death within 24-36 months) are both associated with some molecular features and with a limited response to current treatments.
Copyright (c) 2024 Giuseppe G.M. Leone; Prof. Testa http://creativecommons.org/licenses/by-nc/4.0
Is laboratory monitoring useful in DOACs management?
Copyright (c) 2025 Mario Biglietto, Rosaria Mormile, Matteo Totaro, Maria Laura Bisegna, Cristina Santoro, Antonio Chistolini http://creativecommons.org/licenses/by-nc/4.0
Addition of daratumumab to first-line therapy of newly diagnosed multiple myeloma in patients eligible for autologous stem cell transplantation: a single-center real-life experience
Copyright (c) 2025 Edoardo Olivari http://creativecommons.org/licenses/by-nc/4.0
Thalidomide treatment for thrombocytopenia secondary to hypersplenism in children with β-thalassemia major: a case series
Copyright (c) 2025 Kun Yang http://creativecommons.org/licenses/by-nc/4.0
Genetically Predicted Antibody Levels as a Proxy for Helicobacter pylori Infection
Copyright (c) 2025 Nawfal R Hussein http://creativecommons.org/licenses/by-nc/4.0
Antimicrobial Stewardship in a world racked by conflict and uncertainty: A Call for global resilience
its not necessary for the tetter to the editor
Copyright (c) 2025 Edmond Puca, Lul Raka, Najada Como, Entela Puca, Monika Fida, Mustafa Altındiş http://creativecommons.org/licenses/by-nc/4.0
Successful Management of Steroid-Resistant cutaneous Acute Graft-versus-Host Disease, Toxic Epidermal Necrolysis-Like, with Ruxolitinib
A case of Acute graft-versus-host disease (aGVHD) with severe cutaneous manifestations resembling Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is presented.
Copyright (c) 2025 Fahir Ozturk, Mehmet Sezgin Pepeler, Esra Ucaryilmaz Ozhamam, Gulten Korkmaz http://creativecommons.org/licenses/by-nc/4.0
THE Co-Occurrence of Jak2/Calr-Positive Myeloproliferative Disorder and Bcr-Abl-Positive Chronic Myelogenous Leukaemia Treated with Combination of Tyrosine Kinase Inhibitors and Ruxolitinib.
The concomitant presence of BCR-Abl1 and JAK2/CALR mutations in Myeloproliferative neoplasms (MPNs) is rare. The clinical presentation of Chronic Myelogenous Leukemia (CML) and Ph-negative MPN may vary, but CML seems to play a dominant role, so patients usually receive treatment with tyrosine kinase inhibitor (TKI) only. The second Ph-negative MPN becomes evident under the selective pressure of the TK.I.
Copyright (c) 2025 Katia Paciaroni, Selenia Campagna, Nicoletta Villiva', Enrico Maffini, Francesca Celesti, Attilio Tordi, Mariangela Lombardi, Giulia Dragonetti, Tommaso Caravita di Toritto http://creativecommons.org/licenses/by-nc/4.0
A case of severe gastrointestinal toxicity after allogeneic hematopoietic stem cell transplantation: can we improve the evaluation of the “gut fitness“ ?
Copyright (c) 2025 Gabriele Magliano, Enrico Morello, Mirko Farina, Vera Radici, Marco Galli, giulia brambilla, Michele Malagola, Domenico Russo, Daniele Avenoso http://creativecommons.org/licenses/by-nc/4.0
Monoclonal gammopathy of neurological significance: a case report and a novel approach
There is increasing evidence regarding gammopathy of clinical significance (MGCS), conditions in which there is paraprotein-mediated tissue and organ damage via mechanisms independent of tumor growth. There is no standard treatment for these novel entities. We describe a case of a 61 years old male presenting with a monoclonal gammopathy of neurological significance (MGNS) treated with four weekly doses of Rituximab (RTX), without benefit, and then with a novel protocol.
Copyright (c) 2025 Mario Biglietto, Martina Gherardini, Raffaele Maglione, Azzurra Anna Romeo, Luciano Fiori, Piera Giovangrossi, Alessandro Pulsoni, Ugo Coppetelli http://creativecommons.org/licenses/by-nc/4.0
Direct oral anticoagulants (DOACs) in the onco-hematologic patients
Copyright (c) 2025 Mario Biglietto, Silvio Ligia, Alessandro Laganà, Giovanni Manfredi Assanto, Martina Gherardini, Erminia Baldacci, Cristina Santoro, Antonio Chistolini http://creativecommons.org/licenses/by-nc/4.0
Interstitial pneumonia triggered by H1N1 influenza A virus as the initial presentation of chronic myeloid leukemia
Copyright (c) 2025 Zhan Su, Feng Wang http://creativecommons.org/licenses/by-nc/4.0
Clinical Manifestation of Children with Kawasaki Disease during the COVID-19 Pandemic in Iran: A Case Series
The aim of the present study was to investigate the various characteristics of Kawasaki disease in children during the COVID-19 pandemic.
Copyright (c) 2025 zahra Fotokian http://creativecommons.org/licenses/by-nc/4.0
Efficacy and safety of teclistamab followed by autologous stem cells transplant in functional high-risk and triple class refractory multiple myeloma
Copyright (c) 2025 Vincenzo Sammartano, Sara Ciofini, Beatrice Esposito Vangone, Chiara Carrara, Monica Bocchia, Alessandro Gozzetti http://creativecommons.org/licenses/by-nc/4.0
Isavuconazole successfully treated pulmonary mucormycosis in acute myeloid leukemia: A case report
Copyright (c) 2025 Hong Chen, Kun Chen, wenqiang kong http://creativecommons.org/licenses/by-nc/4.0
COVID-19-associated cold agglutinin syndrome and hemophagocytic phenomenon in a patient with monoclonal gammopathy of undetermined significance
This manuscript presents a rare case of cold agglutinin syndrome (CAS) and the hemophagocytic phenomenon as complications of COVID-19, highlighting the role of monoclonal gammopathy of undetermined significance (MGUS) in the pathophysiology of these conditions.
CMV Reactivations During and after Letermovir Prophylaxis In Allogeneic Hematopoietic Stem Cell Transplantation: a Single-Center Experience.
Fecal microbiota transplantation as a salvage therapy for concomitant resistant digestive graft versus host disease and cryptosporidiosis in a patient post hematopoietic stem cell transplant : about a case
Chronic myeloid leukemia (CML) is a hematologic malignancy characterized by an uncontrolled proliferation of myeloid cells, particularly neutrophils. It is revealed through the detection of a Philadelphia chromosome (BCR;ABL). While tyrosine kinase inhibitors have dramatically improved short and middle-term outcomes, in some resistant or relapsing cases, allogeneic hematopoietic stem cell transplantation (HSCT) can be a curative option. In this first-ever documented case, we report the successful use of fecal microbiota transplantation (FMT) to treat both corticosteroid-resistant gastrointestinal GvHD and concomitant cryptosporidiosis, leading to significant clinical improvement in a patient post umbilical cord blood HSCT.
Copyright (c) 2025 Thomas Finotto, Carole Chevenet, Amandine Fayard http://creativecommons.org/licenses/by-nc/4.0
Fusion Gene Landscape in a Case of Acute Myelocytic Leukemia with Myelocyte Morphology
Copyright (c) 2024 Zhan Su, Yan Li, Haidong Zhu, Yaqi Wang, Meiying Yang http://creativecommons.org/licenses/by-nc/4.0
West Nile Virus Encephalitis in A Patient with Chronic Lymphocytic Leukemia
Copyright (c) 2024 Giovanni D'Arena, Carmela Palladino, Michele Bosco, Michele Gambardella http://creativecommons.org/licenses/by-nc/4.0
A case of multiple myeloma in a patient in treatment for chronic lymphocytic leukemia
Synchronous and sequential diagnosis of Multiple Myeloma (MM) and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) is a rare event with no cases described with a need for concomitant treatment for both diseases. Here we describe a case of a 58 years old male patient diagnosed with CLL and then MM, needing concomitant treatment for both diseases. We treated the patient with a BELLINI trial-like regimen including Bortezomib, Venetoclax and Dexamethasone, obtaining a good response for both the malignancies.
Copyright (c) 2025 Mario Biglietto, Ugo Coppetelli, Luciano Fiori, Martina Gherardini, Raffaele Maglione, Alessandro Pulsoni, Azzurra Anna Romeo http://creativecommons.org/licenses/by-nc/4.0
Risk Factors of Hepatitis B Virus Infection in the Kurdistan Region of Iraq: A Cross-Sectional Study
Abstract Background and Objectives: Hepatitis B virus (HBV) poses a significant public health challenge worldwide, contributing to substantial morbidity and mortality. Despite the availability of effective vaccines, immunoglobulins and antiviral medications, HBV prevalence remains high in developing regions. This study investigates the potential risk factors associated with HBV infection in the Kurdistan region of Iraq to aid in developing targeted prevention strategies. Design and Methods: A cross-sectional study was conducted involving 4091 participants from Duhok and Zakho, in Kurdistan region of Iraq. Data on demographics and potential risk factors were collected via a structured questionnaire. HBV surface antigen (HBsAg) was screened using enzyme-linked immunosorbent assay (ELISA) to determine infection status. Statistical analysis included univariate and multivariate logistic regression to identify independent risk factors. Results: The mean age of enrolled participants was 29.33 years ± 10.74. Among them, 2851/4091 (69.69%) were females, 3385/4091 (82.74%) were residents of city and 3682/4091 (88.68%) were married. The prevalence of HBV infection among them was 3.67% (150/4091) and the following factors were significantly associated with HBV infection: female gender (p = 0.001), rural residency (p = 0.001), being married (p = 0.0014). Though a history of general operation and tattooing was found to be associated with HBV infection, this association was lost in multivariate analysis (p > 0.05) possibly due to confounding effect. A history of receiving blood or dental procedure was not significantly associated with HBV infection (p > 0.05). Conclusion: The prevalence of HBV infection in Duhok and Zakho remains high and several predictive factors were identified which can be used to target infection control measures. Future research should focus on a population-based study to investigate the prevalence and risk factors of HBV infection to better inform public health policies.
Copyright (c) 2025 Nawfal R Hussein, Halder J Abozait, Ibrahim A Naqid, Nashwan MR Ibrahim, Fatima K Khalid, Dildar H Musa, Zana SM Saleem http://creativecommons.org/licenses/by-nc/4.0
Bladder microbiota snapshots help to monitor urinary tract infections in vulnerable patients
The development of next generation sequencing technology has undoubtedly impairs the classic microbiological approach even though main questions remain still elusive. To date, nobody can define the existence of a unique healthy microbial community, nor a diagnostic application can be definitely assessed. In this context, “snapshots” of the microbiota contribute to reveal factors associated with a disease, even though lacking longitudinal data and the association with results obtained from gold standard microbiological tests. Here we show how the information obtained by microbiota can be a promising additional tool to monitor urinary tract infections revaluating beneficial communities or attention to particularly microbial patterns.
Copyright (c) 2025 Giulia Santarelli, Delia Mercedes Bianco, Margherita Capriati, Maurizio Sanguinetti, Claudia Rendeli, Flavio De Maio http://creativecommons.org/licenses/by-nc/4.0
Late-Onset Veno-Occlusive Disease (VOD) Post-Haploidentical Transplant: A Diagnostic Challenge Requiring Liver Biopsy– A Case Report
Abstract Background: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication post-hematopoietic stem cell transplantation (HSCT), classically presenting within the first 3 weeks. However, late-onset VOD, often presenting beyond day +21, may lack the classical hallmarks, making diagnosis particularly challenging. Case Presentation: We report a 41-year-old female with adverse-risk acute myeloid leukemia (AML) who underwent haploidentical HSCT in first complete remission. On day +35, she developed hemorrhagic cystitis due to BK polyomavirus and CMV viremia, followed by progressive abdominal distension, hepatomegaly, ascites, and mild hyperbilirubinemia. Initial imaging and laboratory investigations were non-specific. A diagnostic transjugular liver biopsy performed on day +52 revealed classical features of SOS with zone 3 perisinusoidal fibrosis. She was managed conservatively with complete clinical resolution. Conclusion: This case highlights the diagnostic complexity of late-onset VOD and reinforces the indispensable role of liver biopsy when conventional criteria are inconclusive.
Copyright (c) 2025 Mehak Trehan, Homdutt Sharma, Abhinav Sengupta, Anirudh Burli, Pradeep Kumar, Manoranjan Mahapatra http://creativecommons.org/licenses/by-nc/4.0
Luspatercept Treatment in a β-Thalassemia Patient with Pulmonary Arterial Hypertension: A Case Report
β-Thalassemia is associated with a range of complications, with pulmonary hypertension in affected individuals having a particularly high mortality rate. However, data on the use of pulmonary vasodilators in β-thalassemia are scarce. Here, we present the case of an adult male diagnosed with β-thalassemia and pulmonary hypertension. There was no improvement in symptoms or test results with low-dose Riociguat. After taking Luspatercept, the patient's hemoglobin level increased significantly. Notably, his PAH symptoms also improved, as reflected by better 6-minute walk test results and reduced tricuspid regurgitation velocity on echocardiography. These findings suggest that Luspatercept may be useful in reducing pulmonary vascular resistance and improving clinical outcomes in patients with β-thalassemia and pulmonary hypertension.">β-Thalassemia is associated with a range of complications, with pulmonary hypertension in affected individuals having a particularly high mortality rate. However, data on the use of pulmonary vasodilators in β-thalassemia are scarce. Here, we present the case of an adult male diagnosed with β-thalassemia and pulmonary hypertension. There was no improvement in symptoms or test results with low-dose Riociguat. After taking Luspatercept, the patient's hemoglobin level increased significantly. Notably, his PAH symptoms also improved, as reflected by better 6-minute walk test results and reduced tricuspid regurgitation velocity on echocardiography. These findings suggest that Luspatercept may be useful in reducing pulmonary vascular resistance and improving clinical outcomes in patients with β-thalassemia and pulmonary hypertension.
Copyright (c) 2025 beibei yang, dongmei liu, changyu yang, Yali zhou, Guiping Liao, jian huang, Yingying Li, yinjiang tang, xiaolin yin http://creativecommons.org/licenses/by-nc/4.0
Prevention of Early Death in Very Elderly Acute Promyelocytic Leukemia Patients Using Lower Induction Doses of All-trans Retinoic Acid
Copyright (c) 2025 Mark Dalgetty, Sruthi Dontu, Chandini Kannan, Amany Keruakous, Locke Bryan, Vamsi Kota, Anand Jillella http://creativecommons.org/licenses/by-nc/4.0
COVID-19 induces prolonged immunological exhaustion leading to relapse of hematological malignancies except in hematopoietic cell transplant recipients
We studied the impact of COVID-19 on relapse in patients with hematological malignancies who had achieved complete remission (CR) and were either treatment-free or maintained on uninterrupted therapy over a 24-month period, excluding patients who relapsed or succumbed to the infection within 30 days.
Copyright (c) 2025 SUPARNO CHAKRABARTI, Snigdha Banerjee, Mahak Agarwal, Gitali Bhagawati, Nilanjan Saha, SARITA JAISWAL http://creativecommons.org/licenses/by-nc/4.0
Clinical spectrum and genotypes of children with alpha-thalassemia in northeastern, Thailand
Background: Alpha-thalassemia is a common inherited hemoglobin disorder. Hemoglobin H (Hb H) disease, a form of alpha-thalassemia caused by the inactivation of three α-globin genes through deletional or non-deletional mutations, presents with a broad clinical spectrum, ranging from non-transfusion-dependent thalassemia (NTDT) to transfusion-dependent thalassemia (TDT). Objective: To characterize the clinical manifestations and genetic diversity of alpha-thalassemia in pediatric patients.
Copyright (c) 2025 Patcharee Komvilaisak, Nattakarn Sangkha, Arunee Jetsrisuparp, Kunanya Suwannaying1 Suwannaying, Goonnapa Fucharoen, Napat Laoaroon http://creativecommons.org/licenses/by-nc/4.0
Zanubrutinib as upfront treatment in de-novo B-cell prolymphocytic leukemia: the case of two elderlies.
B-cell prolymphocytic leukemia (B-PLL) is a rare lymphoproliferative disorder characterized by splenomegaly, lymphocytosis, and poor prognosis. Treatment options are limited, with modest responses to chemo-immunotherapy. We present two elderly patients with B-PLL treated with Zanubrutinib, a second-generation BTK inhibitor, achieving good disease response and tolerance. Both had TP53 deletion/mutations and high-risk complex karyotype. They obtained partial remission with normalization of hematologic parameters and spleen size. Given the rarity of the disease, further studies are needed to define treatment strategies, but Zanubrutinib appears to be a promising drug in this rare orphan drug disease.
Copyright (c) 2025 Silvia Giorgi, Giovanna Leonardi, Monica Maccaferri, Elena Sbadili, Carlo Caterina, Giovanni Fera, Ambra Paolini, Leonardo Potenza, Anna Candoni, Mario Luppi, Roberto Marasca http://creativecommons.org/licenses/by-nc/4.0
Early use of thrombopoietin receptor agonists (Tpo-Ras) in clinical practice: results from an Italian survey on behalf of the GIMEMA Working Group Anemia and Thrombocytopenia
Copyright (c) 2025 Mariasanta Napolitano, elisa lucchini, maria rosaria de paolis, antonio urso, nicola vianelli, francesco zaja, cristina santoro http://creativecommons.org/licenses/by-nc/4.0
Elevated endogenous alveolar carbon monoxide concentration in patients with transfusion-dependent thalassemia and its relation to ineffective erythropoiesis
Blood transfusion is a principal treatment for thalassemia at present, but there is still an absence of effective examination to evaluate the efficacy of blood transfusion and judge the timing of blood transfusion. Carbon monoxide (CO) breath test is a non-invasive and rapid examination way that could dynamically monitor red blood cell destruction in patients with thalassemia. A total of 61 patients with transfusion-dependent thalassemia and 21 healthy controls were recruited in the study.
Copyright (c) 2025 yanni xie http://creativecommons.org/licenses/by-nc/4.0
Long-term persistence of dysplastic features in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and arsenic trioxide
The introduction of arsenic trioxid (ATO) associated to all-trans retinoic acid (ATRA) is the therapeutic standard for standard-risk acute promyelocytic leukemia (APL). ATO has been shown to induce dysplastic changes on bone marrow progenitor cells. Despite that, observational studies evaluating bone marrow morphology during follow-up of APL patients treated with the ATRA-ATO combination are lacking. Hence, we conducted a retrospective study to evaluate morphological characteristics of bone marrow smears at different time-points during the follow up of 8 patients successfully treated with ATRA-ATO (end of consolidaton and 12 monts after end of therapy), as compared to those of 3 patients treated with the AIDA protocol. At 12 months after end of treatment, we highlighted higher grade of megakaryocytic dysplasia and increased promonocyte counts in patients treated with ATRA/ATO versus AIDA (p=0.026 and p=0.030 respectively), suggesting a long-term dysplastic effect of arsenic trioxide. Despite the morphological alterations described, none of the patients treated with ATRA-ATO developed cytopenia or a secondary myeloid neoplasm during follow-up, configuring an “idiopathic dysplasia of unknown significance” (IDUS).
Copyright (c) 2025 Enrico Santinelli, Maria Rosaria Pascale, Luca Guarnera, Arianna Savi, Flavia Mallegni, Carmelo Gurnari, Luca Maurillo, Maria Teresa Voso, Susanna Fenu http://creativecommons.org/licenses/by-nc/4.0
Genetic modulators of diversity in biological expression of sickle cell anemia in patients from democratic republic of Congo
Background: So far, the fetal hemoglobin (HbF) level is the most recognized modulator of sickle cell anemia (SCA) clinical expression. Variability in the HbF levels is associated with the SCA haplotypes and quantitative trait loci identified by Genome-Wide Association Studies (GWAS). Key words: sickle cell anemia, DR Congo, SCA haplotypes, HbF, single nucleotide polymorphisms
Copyright (c) 2024 MAMY NGOLE, MAMY NGOLE, GLOIRE MBAYABO, PAUL LUMBALA, VALERIE RACE, NONO MVUAMA, STEPHANIE DEMAN, ERIKA SOUCHE, PROSPER TSHILOBO LUKUSA, CHRIS VAN GEET, KOENRAAD DEVRIENDT, GERT MATTHIJS, AIME LUMAKA, ISABELLE CLEYNEN http://creativecommons.org/licenses/by-nc/4.0
Anti-mullerian hormone evaluates ovarian function in patients with non-transfusion-dependent thalassemia
Objective: This study analyzed anti-mullerian hormone (AMH) levels in patients with non-transfusion-dependent thalassemia (NTDT) to evaluate their ovarian function.
Copyright (c) 2024 Yan Li, Kun Yang, Yali Zhou, Shiwu Cheng http://creativecommons.org/licenses/by-nc/4.0
The diagnostic sensitivity of beta-D-glucan assay in patients with chronic disseminated candidiasis
Objectives: Chronic disseminated candidiasis (CDC) is a specific syndrome in patients with hematologic malignancies which usually occurs after the recovery of neutrophils due to previous chemotherapy. The beta-D-glucan (BDG) assay has been proposed as an adjunct test for diagnosing invasive fungal infection. However, data on BDG assay in patients with CDC are scarce. We aimed to investigate the diagnostic sensitivity of BDG assay in patients with CDC. Methods: All adult patients who were diagnosed as CDC in a tertiary hospital in Seoul, South Korea, from January 2017 to December 2019 and underwent BDG assay (Gold Mountain River Tech Development, Beijing, China) were retrospectively reviewed. CDC was defined by the demonstration of small, target-like abscesses in the liver or spleen (bull’s-eye lesions) or in the brain at the time of neutrophil recovery after a prolonged phase of neutropenia. The values for BDG over 80 pg/mL were classified as positive. Results: A total of 20 patients were enrolled. The median age was 51 years (IQR 39 – 64). Of these, 13 patients had AML, 3 ALL, 2 MDS, and 1 aplastic anemia. Candida spp. were isolated in 6 patients; 3 were C. tropicalis, 2 C. glabrata, and 1 C. krusei. Of the 20 patients, 10 (50%) revealed positive BDG results. The median BDG value was 174 pg/dL (IQR 137–402). More CDC patients with previous candidemia had positive BDG assay than those without candidemia, but with no statistical significance (4/5 (80%) vs. 6/15 (40%), P = 0.30). In the 7 patients with BDG assay-positive CDC, for whom follow-up BDG results were available, the BDG remained high in 6 patients (86%) for more than 4 weeks after adequate antifungal therapy. All 4 patients who died had a positive BDG assay, and 3 of them showed an increasing trend of BDG values during treatment. Conclusions: Negative BDG assay appears to be not useful to rule out CDC. BDG assay decreased slowly during the adequate treatment of CDC.
Copyright (c) 2024 Hyo Ju Son, Kyung Hwa Jung http://creativecommons.org/licenses/by-nc/4.0
Leukemia cutis in a patient with acute myeloid leukemia undergoing Azacitidine-Venetoclax: case presentation and review of the literature
Leukemia cutis (LC) is a rare extramedullary localization of acute myeloid leukemia (AML). LC management generally relies on AML treatment, namely intensive chemotherapy (IC). In frail patients with LC, viable options are hypomethylating agents (HMA) associated with Venetoclax, but literature about their use is scarce. Here, we report our experience and a short review of the previous cases of LC treated with HMA plus Venetoclax to underline the efficacy of such treatment in LC patients unsuitable for IC.
Copyright (c) 2025 Elisa Buzzatti, Cristina Mauro, Caterina Botti, Roberta Presicci, Giovangiacinto Paterno, Raffaele Palmieri, Carmelo Gurnari, Flavia Mallegni, Elisa Meddi, Federico Moretti, Lucia Cardillo, Valeria Mezzanotte, Kristian Taka, Lucrezia De Marchi, Luca Maurillo, Francesco Buccisano, Adriano Venditti, Maria Ilaria Del Principe http://creativecommons.org/licenses/by-nc/4.0