Hematological Research Articles

Mandibular analysis of Beta thalassemia patients from hematological institutes of Karachi Pakistan.

Objective: To study the mandibular changes in the β-thalassemia major patient. Study Design: Cross sectional study. Setting: Husaini Blood Bank and Institute of Hematological Diseases Karachi, Department of Oral and Maxillofacial Surgery, and Department of Orthodontics, Baqai Dental College Baqai Medical University, Karachi. Period: January 2023-December 2023. Methods: 50 Orthopanthogram (OPG) radiographs of beta-thalassemia major patient were taken, analyzed and compared to check any variation from normal. Fifty diagnosed β-thalassemia major patients were voluntarily selected through convenience sampling. The study was carried out in collaboration of Husaini Institute of Blood Diseases Karachi, National institute of Oral Diseases Karachi Pakistan and, Department of Oral and Maxillofacial Surgery and department of orthodontics Baqai Dental College Baqai Medical University. Results: 18 (36%) patient’s alteration of trabecular pattern are present and in 32 (64%) patient alteration of trabecular pattern absent. Similarly, in 16 (32%) patients have short spiky roots are present and 34 (68%) patients short spiky roots absent. Conclusion: Effect of anemia is not so profound in mandible of thalassemia patients from population of Karachi.

The Effect of Oral Care Protocols on Mucositis in Pediatric Cancer Patients: A Randomized Controlled Trial

Background/Aims: Standard oral care protocols can reduce the incidence of mucositis. This study aimed to evaluate the effect of the "Oral Care Protocol" containing sodium bicarbonate or saline on mucositis development, degree, and duration in pediatric cancer patients. Methods: This study is a blind, parallel trial design, randomized controlled study. Patients (n = 43) who received inpatient chemotherapy treatment for more than three days at the Pediatric Hematology and Oncology Unit were included. The oral care protocol with saline was given to the patients in the control group (n = 22), and the oral care protocol with sodium bicarbonate was given to the patients in the study group (n = 21). The primary outcome was the development of mucositis. The secondary outcomes were mucositis degree, patient data at the time of mucositis development, and the duration of mucositis. The characteristics of the patients in the study and control groups and the data of patients with and without mucositis were compared with Fisher's exact test, t-test, and chi-square analysis. Results: No statistically significant difference was found between the study and control groups in terms of mean age, gender, diagnosis, relapse status, treatment stage, risk group, and treatment protocols. Mucositis developed in 18.2% of the patients in the control group and 9.5% of the patients in the study group. No statistically significant difference was found in terms of mucositis development, degree, and duration. Conclusions: The oral care protocol with sodium bicarbonate can be used to prevent mucositis in pediatric cancer patients. ClinicalTrials.gov Identifier: NCTXXX.

A case of pediatric brain abscess secondary to rhinosinusitis

Acute bacterial rhinosinusitis is a common childhood infection and a frequent complication of viral infections or allergic inflammations of the upper respiratory tract. Untreated cases may have serious complications as meningitis, orbital cellulitis, epidural and brain abscesses (1,2). Brain abscesses rarely seen pediatric infections with high mortality and morbidity rates, are mostly observed secondary to extrasinus spread of rhinosinusitis and acute otitis media, hematogenous spread and penetrating trauma (3). The most common predisposing factors are immunodeficiencies, cyanotic heart and hematologic diseases. A 16-year-old boy was admitted to the emergency service due to seizure. It was learned from his history that he was admitted to the hospital 10 days ago due to headache and high fever. With the diagnosis of acute sinusitis, azithromycin and ornidazole treatment was started, but there was no improvement in his complaints.. On physical examination, clouding of consciousness and postnasal purulent discharge were detected. Remarkable laboratory test results: WBC: 22.500/mm3; platelets 156.000/mm3, C-reactive protein 226 mg/L. Brain tomography revealed a 4-cm suspicious abscess or mass lesion in the right frontal region of the brain compatible with right frontal and ethmoid sinusitis. Upon consultation with pediatric neurology and neurosurgery departments, cranial MRI and MR spectrometry were performed which revealed a lesion compatible with a 4- cm brain abscess, brain edema , shift, and acute sinusitis in the right frontal region. Treatment with cefotaxime, vancomycin and metroinidazole was started for acute sinusitis, and hypertonic sodium infusion and leveteresitam treatment for brain edema. Surgical drainage of the abscess > 2 cm was performed by neurosurgery. Gram staining and culture of the abscess material were unremarkable. Upon evaluation by pediatric immunology, cardiology and hematology departments, immunodeficiency, cyanotic heart disease and hematologic disease were not detected. The lesion was evaluated as inappropriately treated brain abscess secondary to acute sinusitis. In the 2nd week of treatment, edema surrounding the abscess, shift and pressure regressed, but the the abscess did not shrink, so the treatment with meropenem, vancomycin and metroinidazole was initiated. Antiedema therapy was discontinued, and antibiotherapy was maintained for 9 weeks until the abscess size was < 2 cm. When the abscess shrinked below 1 cm in the control cranial images he was discharged with follow-up recommendations. Acute bacterial sinusitis is one of the common, and clinically diagnosed infectious diseases of childhood. And current guidelines recommend amoxicillin, amoxicillin-clavulanic acid and cephalosporins (ie.cefdinir) as the first-line treatment. Considering the high drug resistance in our country, macrolides are not the first choice in patients without a history of penicillin allergy (2). If not treated appropriately, serious cranial complications preventable with timely appropriate antibiotherapy may develop. Brain abscesses are rare but mortal infectious diseases in childhood. The most common cause is the extrasinus spread of infections such as acute rhinosinusitis (3). Combination of medical and surgical treatment is usually recommended for abscesses > 2 cm. For abscesses < 2 cm and inoperable multiple abscesses only medical treatment is an option. Although the duration of treatment depends on the size, location, causative agent and treatment response, medical treatment is recommended for approximately 6-12 weeks until the abscess is < 2 cm (4)

In utero delivery of targeted ionizable lipid nanoparticles facilitates in vivo gene editing of hematopoietic stem cells

Monogenic blood diseases are among the most common genetic disorders worldwide. These diseases result in significant pediatric and adult morbidity, and some can result in death prior to birth. Novel ex vivo hematopoietic stem cell (HSC) gene editing therapies hold tremendous promise to alter the therapeutic landscape but are not without potential limitations. In vivo gene editing therapies offer a potentially safer and more accessible treatment for these diseases but are hindered by a lack of delivery vectors targeting HSCs, which reside in the difficult-to-access bone marrow niche. Here, we propose that this biological barrier can be overcome by taking advantage of HSC residence in the easily accessible liver during fetal development. To facilitate the delivery of gene editing cargo to fetal HSCs, we developed an ionizable lipid nanoparticle (LNP) platform targeting the CD45 receptor on the surface of HSCs. After validating that targeted LNPs improved messenger ribonucleic acid (mRNA) delivery to hematopoietic lineage cells via a CD45-specific mechanism in vitro, we demonstrated that this platform mediated safe, potent, and long-term gene modulation of HSCs in vivo in multiple mouse models. We further optimized this LNP platform in vitro to encapsulate and deliver CRISPR-based nucleic acid cargos. Finally, we showed that optimized and targeted LNPs enhanced gene editing at a proof-of-concept locus in fetal HSCs after a single in utero intravenous injection. By targeting HSCs in vivo during fetal development, our Systematically optimized Targeted Editing Machinery (STEM) LNPs may provide a translatable strategy to treat monogenic blood diseases before birth.

Impact of Dedicated Thalassemia Day Care Services: Pediatric Hematologist’s Perspective

Impact of Dedicated Thalassemia Day Care Services: Pediatric Hematologist’s Perspective

Unified Aedes aegypti Protein Resource Database (UAAPRD): An Integrated High-Throughput In Silico Platform for Comprehensive Protein Structure Modeling and Functional Target Analysis to Enhance Vector Control Strategies.

A comprehensive examination of Aedes aegypti's proteome to detect key proteins that can be targeted with small molecules can disrupt blood feeding and disease transmission. However, research currently only focuses on finding repellent-like compounds, limiting studies on identifying unexplored proteins in its proteome. High-throughput analysis generates vast amounts of data, raising concerns about accessibility and usability. Establishing a dedicated database is a solution, centralizing information on identified proteins, functions, and modeled structures for easy access and research. This study focuses on scrutinizing key proteins in A. aegypti, modeling their structures using RaptorX standalone tool, identification of druggable binding sites using BiteNet, validating the models via Ramachandran plot studies and refining them via 50-ns molecular dynamic simulations using Schrodinger Maestro. By analyzing ~ 18k proteins in the proteome of A. aegypti in our previous studies, all proteins involved in the light and dark circadian rhythm of the mosquito, inclusive of proteins in blood feeding, metabolism, etc. were chosen for the current study. The outcome is UAAPRD, a unique repository housing information on hundreds of previously unmodeled and un-simulated mosquito proteins. This robust MYSQL database ( https://uaaprd.onrender.com/user ) houses data on 309 modeled & simulated proteins of A. aegypti. It allows users to obtain protein data, view evolutionary analysis data of the protein categories, visualize proteins of interest, and send request to screen against the pharmacophore models present in UAAPRD against ligand of interest. This study offers crucial insights for developing targeted studies, which will ultimately contribute to more effective vector control strategies.

Improved outcome of COVID-19 over time in patients treated with CAR T-cell therapy: Update of the European COVID-19 multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP) and the European Hematology Association (EHA) Lymphoma Group

COVID-19 has been associated with high mortality in patients treated with Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome has improved over time with the primary objective of assessing COVID-19-attributable mortality in the Omicron period of 2022 compared to previous years. Data for this multicenter study were collected using the MED-A and COVID-19 report forms developed by the EBMT. One-hundred-eighty patients were included in the analysis, 39 diagnosed in 2020, 35 in 2021 and 106 in 2022. The median age was 58.9 years (min-max: 5.2–78.4). There was a successive decrease in COVID-19-related mortality over time (2020: 43.6%, 2021: 22.9%, 2022: 7.5%) and in multivariate analysis year of infection was the strongest predictor of survival (p = 0.0001). Comparing 2022 with 2020–2021, significantly fewer patients had lower respiratory symptoms (21.7% vs 37.8%, p = 0.01), needed oxygen support (25.5% vs 43.2%, p = 0.01), or were admitted to ICU (5.7% vs 33.8%, p = 0.0001). Although COVID-19-related mortality has decreased over time, CAR T-cell recipients remain at higher risk for complications than the general population. Consequently, vigilant monitoring for COVID-19 in patients undergoing B-cell-targeting CAR T-cell treatment is continuously recommended ensuring optimal prevention of infection and advanced state-of-the art treatment when needed.

Unrelated hematopoietic stem cell donor registries: present reality and future prospects.

Stem cell donor registries play an important role in providing stem cell products from unrelated donors to patients with severe blood diseases. In this review, important aspects of donor registry work, current challenges and possible future developments are discussed. The current growth in global unrelated stem cell donations is in line with the long-term trend, indicating that donor registries have overcome the COVID-19 pandemic. A key challenge for donor registries is the recruitment of donors from disadvantaged populations to create greater equity in access to unrelated stem cell transplantation. In addition, recruiting young donors and increasing the availability of donors who are already registered are important goals. In recent years, numerous studies have looked at the context of these themes and the development of possible solutions. The international community of donor registries, together with the World Marrow Donor Association, has helped many patients in need of a stem cell transplant over the past decades and is, therefore, a bright example of international collaboration for a good cause. It is currently addressing a number of challenges to effectively help as many patients as possible from various populations also in the future.

The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

Umbilical cord blood stem cells: transplantation prospects in neurological practice

Umbilical cord blood has evolved from being considered a mere cellular/tissue waste product after childbirth to a valuable biological material with a wide regenerative potential. Today, hematopoietic cord blood stem cells are used in the same way as bone marrow and mobilised peripheral blood as part of the standard medical treatment for haemoblastoses and hereditary blood diseases. There is an increasing amount of experimental data showing possibility of umbilical cord blood cell fractions using for treatment of non-hematological diseases and, in particular, diseases of the central nervous system. One of the key challenges in cell therapy for central nervous system diseases is the choice of cellular material for neurotransplantation. This is particularly relevant for ischemic and traumatic injuries, as well as neurodegenerative diseases. Stem or mature somatic cells prepared for neurotransplantation should have predictable and reproducible characteristics thataccording therapeutic purposes, exactly: trophic and/or neuroprotective action to increase neurons viability in damaged area; axon growth stimulation and myelination; cell matrix restoration or predictable differentiation direction to replace amount of lost brain or spinal cord cells. The fact that umbilical cord blood contains not only hematopoietic, but also various non-hematopoietic stem cells with a wide regenerative potential has become the basis for active use of these cells for neurotransplantation. The proposed review provides historical information about umbilical cord blood introduction into practical medicine, its cellular composition and clinical applications of stem cells various types for children central nervous system diseases treatment, such as ischemic encephalopathy, stroke, cerebral hemorrhage, cerebral palsy, autism, and in adults — for stroke treatment, spinal cord injury and neurodegenerative diseases.

Utilization and Perceptions of Hydroxyurea Therapy Among Adult Patients With Sickle Cell Disease in Al Ahsa, Saudi Arabia: A Cross-Sectional Study.

Sickle cell disease (SCD) is a prevalent genetic disorder characterized by abnormal hemoglobin formation, resulting in severe complications. Hydroxyurea (HU) therapy has demonstrated efficacy in reducing SCD-related complications; however, its utilization patterns and patient perceptions remain underexplored, particularly in the Al Ahsa region of Saudi Arabia. This cross-sectional study aimed to assess the prevalence of HU usage among adult patients with SCD in Al Ahsa; identify the barriers to starting, maintaining, and discontinuing HU therapy; and evaluate the patient-reported outcomes associated with its use. Data were collected through face-to-face surveys and medical record reviews of adult SCD patients attending outpatient clinics in the Hereditary Blood Diseases Center of Al Ahsa, Saudi Arabia, between December 2023 and March 2024. Descriptive statistics and inferential analyses were performed using SPSS version 26. A total of 345 adult SCD patients were included, with a mean age of 34.12 ± 11.1 years. Most participants were male (58.6%) and unmarried (55.4%). HU utilization was reported by 57.1% of the participants, with the highest adherence observed among older age groups (p = 0.001). Significant improvements in pain severity, hospitalization rates, and quality of life were reported among HU users (p < 0.001). Common barriers to HU use included concerns about side effects, lack of medical justification, and absence of medical advice. This study provides valuable insights into theutilization and perceptions of HU therapy among adults with SCDin Al Ahsa, Saudi Arabia. Addressing identified barriers and promoting patient education are crucial for optimizing therapy adherence and improving clinical outcomes in this population.

Clinical features and prognostic factors of advanced myelodysplastic syndromes in children

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 μg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

Neonatal Leukaemia: A Case Report and Review of the Literature

&amp;lt;i&amp;gt;Background:&amp;lt;/i&amp;gt; Acute leukemia has a particularly bad prognosis in the newborn era. Its prognosis is significantly poorer than in older youngsters. The occurrence of leukaemia in the neonatal period can present diagnostic challenges due to the rarity of the condition and its clinical presentation, which may be misleading or inconspicuous. &amp;lt;i&amp;gt;Case report:&amp;lt;/i&amp;gt; A case of neonatal acute myeloblastic leukaemia (AML) in a newborn with trisomy 21 is presented herein. The patient was admitted with respiratory distress and a clinical examination revealed a facial dysmorphic syndrome, pallor, hepatosplenomegaly, and a bone marrow failure syndrome with bone marrow invasion by 36% myeloblasts, confirming the diagnosis of AML. The immunophenotyping results indicated that the patient had AML0, with a low CD13+ and CD33+ MPO myeloid population. During the patient&amp;apos;s hospitalisation, a multi-resistant Klebsiella pneumoniae urinary tract infection was diagnosed, and septic shock was diagnosed after four days. &amp;lt;i&amp;gt;Conclusion:&amp;lt;/i&amp;gt; Acute neonatal leukaemia is a rare and complex condition that requires the expertise of both neonatologists and paediatric haematologists.

Approach to Glomerular Disease in Pregnancy

The presence of glomerular diseases in pregnancy presents challenges to both patients and nephrologists. The preconception planning in patients with kidney disease involves comprehensive stratification, treatment optimization, and comorbidity assessment, requiring nephrologists to engage in well-informed decision-making processes alongside their patients. There is a necessity for a multidisciplinary approach to meet their complex healthcare needs. Effective control of blood pressure, proteinuria, and disease activity are pivotal in mitigating adverse pregnancy events. This comprehensive review intends to equip nephrologists with the requisite knowledge and understanding to navigate the intricate landscape of glomerular diseases in pregnancy. It delves into the challenges associated with the diagnosis of glomerular diseases, the significance of preconception counseling, and the nuances of antenatal and postnatal care. Additionally, the article provides insights into the management and prognosis of glomerular diseases, shedding light on the judicious use of immunosuppression as a therapeutic tool.

Infections with Klebsiella pneumoniae in Children Undergoing Anticancer Therapy or Hematopoietic Cell Transplantation: A Multicenter Nationwide Study.

Background:Klebsiella pneumoniae is a nosocomial pathogen that causes severe infections in immunocompromised patients. The aim of the study was to conduct a microbiological and clinical analysis of K. pneumoniae infections in children with malignancies or undergoing hematopoietic cell transplantation in Poland. Methods: We conducted a retrospective, multicenter study including children and adolescents under 19 years old treated between 2012 and 2021. We analyzed patients' characteristics, microbiological data, and the outcomes of antibiotic therapy. Results: A total of 9121 newly diagnosed children were treated for malignancy and 1697 pediatric patients underwent hematopoietic cell transplantation. K. pneumoniae infections were diagnosed in 527 patients. Their overall incidence was 4.86% in pediatric hematology and oncology patients and 4.95% in patients who underwent hematopoietic cell transplantation. The incidence of infection was higher in patients with acute leukemia than with solid tumors (7.8% vs. 4.1%; OR = 2.0; 95% CI = 1.6-2.4; p < 0.0001). The most frequent source of infection was in the urinary tract at 55.2%. More than 57% of K. pneumoniae strains were extended-spectrum β-lactamase-positive and almost 34% were multidrug-resistant. Infections with K. pneumoniae contributed to death in 3.22% of patients. Conclusions: K. pneumoniae is one of the most critical pathogens in children suffering from malignancies or undergoing hematopoietic cell transplantation. The incidence of multidrug-resistant K. pneumoniae strains is increasing and contributing to poor clinical outcome.

Survival rates and extra-regional migration patterns of children and adolescents with cancer in Italy: The 30-year experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP) with the Italian hospital-based registry of pediatric cancer (Mod. 1.01).

Since the 1970s, Italian pediatric oncologists have collaborated through the Italian Association for Pediatric Hematology Oncology (AIEOP) network using a common centralized system for the registration of childhood cancer, known as Model 1.01 (Mod. 1.01). In this study, we report on recruitment trends, extra-regional migration and changes in outcome over time in the Italian population of children (0-14 years) and adolescents (15-19 years) registered and treated within the national AIEOP network in the period between 1989 and 2017. In almost 30 years, a cohort of 43,564 patients with a neoplasia diagnosis was registered in Mod. 1.01. The analysis of national extra-regional migration showed that patients tend to migrate from the South to the North and, to a lesser extent, to the Center of the country. During the study period, migration apparently decreased, especially for lymphohematopoietic diseases, whereas it remained substantial for solid tumors. Our data showed a progressive and significant increase in the cumulative survival 5 years after diagnosis since the 1990s, reaching almost 84% for all patients diagnosed in the last decade. Survival rates of Mod. 1.01 patients are similar to those provided by the main national and international reports showing childhood cancer surveillance estimates. The AIEOP Mod 1.01 has proved to be an invaluable tool from both an epidemiological and a health policy point of view, allowing us, in this study, to examine the survival experience of the largest cohort of Italian pediatric cancer patients with a very long follow-up.

Assessing Psychological Disorders in Turkish Adolescents with Transfusion-Dependent Thalassemia.

We investigated depression and anxiety levels and related psychological disorders in adolescents with transfusion-dependent thalassemia (TDT) in this study. The study was conducted in two pediatric hematology outpatient clinics and included adolescents with TDT (14.8 ± 2.4 years, n = 40) in the study and compared them with the healthy age-matched control group (14.3 ± 2.3 years, n = 62). The Turkish version of the Revised Child Anxiety and Depression Scale (RCADS) was used to determine depression, anxiety, and related psychologic disorders (obsession, panic disorder, social phobia). Depression, anxiety, obsession, panic disorder, and social phobia scores were significantly higher in the patient group compared with the control (all p < 0.05). Ferritin levels were positively correlated with total depression, general anxiety, separation anxiety, and social phobia scores, but transfusion frequency and young age were the confounding factors. Patients in early adolescence and those who require more frequent blood transfusions are at higher risk of developing psychological disorders; routine screening for mood disorders should be warranted. Serum ferritin level may be a good warning indicator for early recognition of psychologic disorders in TDT patients.

Corneal Toxicity in Patients Treated by BELANTAMAB MAFODOTIN: How to Improve and Facilitate Patients Follow-Up Using Refractive Shift?

Purpose: Multiple myeloma (MM) is the second most common neoplastic blood disease worldwide. Belantamab mafodotin is a new antibody conjugate anti-B-cell maturation antigen effective against refractory myelomas. It induces intracorneal microcysts leading to refractive fluctuations. The aim of this study is to assess the value of monitoring refractive fluctuations based on the location of microcystic-like epithelial changes (MECs) to facilitate patient follow-up. Methods: This observational and multicentric study was conducted using data collected from several French centers contacted through secure email through a standardized data collection table. Results: The fluctuation of objective refraction in spherical equivalent confirms a significant myopic shift from peripheral to central forms. A decrease in the best-corrected visual acuity (BCVA), an increase in keratometry, and an increase in central epithelial pachymetry have also been observed when MECs migrate toward the center. Conclusion: The myopization found in our study in patients with central and paracentral MECs is consistent with current literature. Fluctuations in BCVA, keratometry, and epithelial pachymetry are also consistent. This study is the first real-world study and highlights heterogeneity in follow-up, emphasizing the need to establish multidisciplinary follow-up strategies. The analysis of refractive fluctuations appears to be a reproducible and noninvasive screening method that could facilitate patient follow-up without the need for consultation focused on corneal diseases.

The Effect of Hematopoietic Stem Cell Transplantation on Treatment Outcome in Children with Acute Lymphoblastic Leukemia.

Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups. A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients' disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease. Among the 549 screened patients, a total of 418 patients were included in the study; B-ALL (n=379) and T-ALL (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.0016). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.0023) and OS (p=0.0221) when HSCT was done as upfront treatment. HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

The administration of PD-1 and PD-L1 inhibitors in pediatric hematology: a literature review

The discovery of immune checkpoints (IC) has become a landmark event in immuno-oncolog y, improving the understanding of the mechanisms of tumor cells evading immune sur veillance. Based on this, a group of drugs such as immune checkpoint inhibitors (ICIs) were developed, the ef fect of which is due to the rupture of the immunological synapse and recognition by tumor T cells. Currently, ICIs are successfully used in the treatment of a number of malignant neoplasms, improving the indicators of diseasefree and overall sur vival. However, determining the role of these drugs in the treatment of children with tumors of the blood system is the subject of active research. This article presents a review of the literature on topical aspects of the administration of PD-1 and PD-L1 inhibitors in pediatric hematolog y. Their mechanisms of action, ef fectiveness and potential complications of therapy are presented.