The Impact of Qualification and Hospice Education on Staff Attitudes during Palliative Care in Pediatric Oncology Wards-A National Survey.

BACKGROUND: Our knowledge about the attitudes of healthcare staff to palliative care in pediatric oncology is scarce. We aimed to assess their perceptions of palliative care in Hungary and find answers to the question of how to provide good palliative care for children. METHOD: Physicians (n = 30) and nurses (n = 43) working in the field of pediatric oncology (12 of them specialized in hospice care) were interviewed. Palliative care practice (communication, integration of palliative care, professionals' feelings and attitudes, and opportunities for improvement) was assessed by semi-structured interviews evaluated in a mixed quantitative and qualitative way by narrative categorical content analysis and thematic analysis. RESULTS: All providers displayed high negative emotions, positive evaluations, and used many active verbs. Nurses showed higher levels of denial, more self-references, and were more likely to highlight loss. Physicians emphasized the importance of communication regarding adequate or inadequate palliative care. Hospice specialists showed a higher passive verb rate, a lower self-reference, a lower need for psychological support, and a greater emphasis on teamwork and professional aspects. CONCLUSION: Our results show that nurses are more emotionally stressed than doctors in palliative care in pediatric oncology. To our knowledge, a study comparing doctors and nurses in this field has yet to be carried out. Our results suggest that pediatric oncological staff can positively evaluate a child's palliative care despite the emotional strain. Regarding hospices, professional practice in palliative care may be a protective factor in reducing emotional distress and achieving professional well-being.

von Willebrand factor/factor VIII concentrate (Wilate) prophylaxis in children and adults with von Willebrand disease.

ABSTRACT: Long-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in patients with von Willebrand disease (VWD) who have a history of severe and frequent bleeds. However, data from prospective studies are scarce. WIL-31, a prospective, noncontrolled, international phase 3 trial, investigated the efficacy and safety of Wilate prophylaxis in severe patients with VWD. Male and female patients 6 years or older with VWD types 1, 2 (except 2N), or 3 who had completed a prospective, 6-month, on-demand, run-in study (WIL-29) were eligible to receive Wilate prophylaxis for 12 months. At baseline, patients (n = 33) had a median age of 18 years. Six (18%) patients had severe type 1, 5 (15%) had type 2, and 22 (67%) had type 3 VWD. The primary end point of a >50% reduction in mean total annualized bleeding rate (TABR) with Wilate prophylaxis vs prior on-demand treatment was met; mean TABR during prophylaxis was 5.2, representing an 84.4% reduction. The bleeding reduction was consistent across age, sex, and VWD types. The mean spontaneous ABR was 3.2, representing an 86.9% reduction vs on-demand treatment. During prophylaxis, 10 (30.3%) patients had 0 bleeding events and 15 (45.5%) patients had 0 spontaneous bleeding events. Of 173 BEs, 84.4% were minor and 69.9% treated. No serious adverse events related to study treatment and no thrombotic events were recorded. Overall, WIL-31 showed that Wilate prophylaxis was efficacious and well-tolerated in pediatric and adult patients with VWD of all types. The WIL-29 and WIL-31 trials were registered at www.ClinicalTrials.gov as #NCT04053699 and #NCT04052698, respectively.

Salivary Chemical Barrier Proteins in Oral Squamous Cell Carcinoma-Alterations in the Defense Mechanism of the Oral Cavity.

Oral squamous cell carcinoma (OSCC) is one of the most frequent types of head and neck cancer. Despite the genetic and environmental risk factors, OSCC is also associated with microbial infections and/or dysbiosis. The secreted saliva serves as the chemical barrier of the oral cavity and, since OSCC can alter the protein composition of saliva, our aim was to analyze the effect of OSCC on the salivary chemical barrier proteins. Publicly available datasets regarding the analysis of salivary proteins from patients with OSCC and controls were collected and examined in order to identify differentially expressed chemical barrier proteins. Network analysis and gene ontology (GO) classification of the differentially expressed chemical barrier proteins were performed as well. One hundred and twenty-seven proteins showing different expression pattern between the OSCC and control groups were found. Protein-protein interaction networks of up- and down-regulated proteins were constructed and analyzed. The main hub proteins (IL-6, IL-1B, IL-8, TNF, APOA1, APOA2, APOB, APOC3, APOE, and HP) were identified and the enriched GO terms were examined. Our study highlighted the importance of the chemical barrier of saliva in the development of OSCC.

PersonALL: a genetic scoring guide for personalized risk assessment in pediatric B-cell precursor acute lymphoblastic leukemia.

BACKGROUND: Recurrent genetic lesions provide basis for risk assessment in pediatric acute lymphoblastic leukemia (ALL). However, current prognostic classifiers rely on a limited number of predefined sets of alterations. METHODS: Disease-relevant copy number aberrations (CNAs) were screened genome-wide in 260 children with B-cell precursor ALL. Results were integrated with cytogenetic data to improve risk assessment. RESULTS: CNAs were detected in 93.8% (n = 244) of the patients. First, cytogenetic profiles were combined with IKZF1 status (IKZF1normal, IKZF1del and IKZF1plus) and three prognostic subgroups were distinguished with significantly different 5-year event-free survival (EFS) rates, IKAROS-low (n = 215): 86.3%, IKAROS-medium (n = 27): 57.4% and IKAROS-high (n = 18): 37.5%. Second, contribution of genetic aberrations to the clinical outcome was assessed and an aberration-specific score was assigned to each prognostically relevant alteration. By aggregating the scores of aberrations emerging in individual patients, personalized cumulative values were calculated and used for defining four prognostic subgroups with distinct clinical outcomes. Two favorable subgroups included 60% of patients (n = 157) with a 5-year EFS of 96.3% (excellent risk, n = 105) and 87.2% (good risk, n = 52), respectively; while 40% of patients (n = 103) showed high (n = 74) or ultra-poor (n = 29) risk profile (5-year EFS: 67.4% and 39.0%, respectively). CONCLUSIONS: PersonALL, our conceptually novel prognostic classifier considers all combinations of co-segregating genetic alterations, providing a highly personalized patient stratification.

Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Acute Lymphoblastic Leukemia Intercontinental-Berlin-Frankfurt-Münster 2009 Trial.

PURPOSE: The International Berlin-Frankfurt-Münster (BFM) study group conducted a study on pediatric acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) was assessed using flow cytometry (FCM), and the impact of early intensification and methotrexate (MTX) dose on survival was evaluated. PATIENTS AND METHODS: We included 6,187 patients younger than 19 years. MRD by FCM refined the risk group definition previously used in the ALL intercontinental-BFM 2002 study on the basis of age, WBC count, unfavorable genetic aberrations, and treatment response measured morphologically. Patients at intermediate risk (IR) and high risk (HR) were randomly assigned to protocol augmented protocol I phase B (IB) versus IB regimen. MTX doses of 2 versus 5 g/m2 every 2 weeks, four times, were evaluated in precursor B-cell-ALL (pcB-ALL) IR. RESULTS: The 5-year event-free survival (EFS ± SE) and overall survival (OS ± SE) rates were 75.2% ± 0.6% and 82.6% ± 0.5%, respectively. Their values in risk groups were standard risk (n = 624), 90.7% ± 1.4% and 94.7% ± 1.1%; IR (n = 4,111), 77.9% ± 0.7% and 85.7% ± 0.6%; and HR (n = 1,452), 60.8% ± 1.5% and 68.4% ± 1.4%, respectively. MRD by FCM was available in 82.6% of cases. The 5-year EFS rates in patients randomly assigned to protocol IB (n = 1,669) and augmented IB (n = 1,620) were 73.6% ± 1.2% and 72.8% ± 1.2%, respectively (P = .55), while those in patients receiving MTX doses of 2 g/m2 (n = 1,056) and MTX 5 g/m2 (n = 1,027) were 78.8% ± 1.4% and 78.9% ± 1.4%, respectively (P = .84). CONCLUSION: The MRDs were successfully assessed using FCM. An MTX dose of 2 g/m2 was effective in preventing relapse in non-HR pcB-ALL. Augmented IB showed no advantages over the standard IB.[Media: see text].

Next-Generation Sequencing-Based Genomic Profiling of Children with Acute Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) represents a major cause of childhood leukemic mortality, with only a limited number of studies investigating the molecular landscape of the disease. Here, we present an integrative analysis of cytogenetic and molecular profiles of 75 patients with pediatric AML from a multicentric, real-world patient cohort treated according to AML Berlin-Frankfurt-Münster protocols. Targeted next-generation sequencing of 54 genes revealed 17 genes that were recurrently mutated in >5% of patients. Considerable differences were observed in the mutational profiles compared with previous studies, as BCORL1, CUX1, KDM6A, PHF6, and STAG2 mutations were detected at a higher frequency than previously reported, whereas KIT, NRAS, and KRAS were less frequently mutated. Our study identified novel recurrent mutations at diagnosis in the BCORL1 gene in 9% of the patients. Tumor suppressor gene (PHF6, TP53, and WT1) mutations were found to be associated with induction failure and shorter event-free survival, suggesting important roles of these alterations in resistance to therapy and disease progression. Comparison of the mutational landscape at diagnosis and relapse revealed an enrichment of mutations in tumor suppressor genes (16.2% versus 44.4%) and transcription factors (35.1% versus 55.6%) at relapse. Our findings shed further light on the heterogeneity of pediatric AML and identify previously unappreciated alterations that may lead to improved molecular characterization and risk stratification of pediatric AML.

Daily serum phosphate increase as early and reliable indicator of kidney injury in children with leukemia and lymphoma developing tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) and its most serious complication, acute kidney injury (AKI) are one of the emergency conditions in onco-hematology. It is difficult to predict the degree of kidney involvement. Therefore, we studied children with leukemia and lymphoma treated in four Hungarian tertiary centers (inpatient university clinics) retrospectively (2006-2016) from a nephrological aspect. METHOD: Data of 31 pediatric patients were obtained from electronic- and paper-based medical records. Physical status, laboratory test results, treatments, and outcomes were assessed. Patients were analyzed according to both "traditional" TLS groupings, as laboratory TLS or clinical TLS, and nephrological aspect based on pRIFLE classification, as mild or severe AKI. RESULTS: Significant differences were found between the changes in parameters of phosphate homeostasis and urea levels in both classifications. Compared to age-specific normal phosphate ranges, before the development of TLS, hypophosphatemia was common (19/31 cases), while in the post-TLS period, hyperphosphatemia was observed (26/31 cases) most frequently. The rate of daily change in serum phosphate level was significant in the nephrological subgroups, but peaks of serum phosphate level show only a moderate increase. The calculated cut-off value of daily serum phosphate level increased before AKI was 0.32 mmol/L per ROC analysis for severe TLS-AKI. The 24-h urinalysis data of eight patients revealed transiently increased phosphate excretion only in those patients with TLS in whom serum phosphate was elevated in parallel. CONCLUSION: Daily serum phosphate level increase can serve as a prognostic factor for the severity of pediatric TLS, as well as predict the severity of kidney involvement. A higher resolution version of the Graphical abstract is available as Supplementary information.

Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors.

BACKGROUND: The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support methods. Digital drug assignment (DDA) is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers, targets, and targeted agents. DDA has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical trial. The aim of this study was to evaluate the utility of DDA in pediatric oncology. METHODS: Between 2017 and 2020, 103 high-risk pediatric cancer patients (< 21 years) were involved in our precision oncology program, and samples from 100 patients were eligible for further analysis. Tissue or blood samples were analyzed by whole-exome (WES) or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the DDA algorithm for therapeutic decision support. Finally, a molecular tumor board (MTB) evaluated the results to provide therapy recommendations. RESULTS: Of the 100 cases with comprehensive molecular diagnostic data, 88 yielded WES and 12 panel sequencing results. DDA identified matching off-label targeted treatment options (actionability) in 72/100 cases (72%), while 57/100 (57%) showed potential drug resistance. Actionability reached 88% (29/33) by 2020 due to the continuous updates of the evidence database. MTB approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases (78%). The approved therapies had significantly higher aggregated evidence levels (AELs) than dismissed therapies. Filtering of WES results for targeted panels missed important mutations affecting therapy selection. CONCLUSIONS: DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine care of high-risk pediatric cancers. Knowledgebase updates enable automatic interpretation of a continuously expanding gene set, a "virtual" panel, filtered out from genome-wide analysis to always maximize the performance of precision treatment planning.

Hypercitrullination and anti-citrullinated protein antibodies in chronic apical periodontitis, a laboratory investigation. Does autoimmunity contribute to the pathogenesis?

AIM: The presence of Gram-negative anaerobic bacteria, in particular, Porphyromonas gingivalis (P. gingivalis) in periapical granulomas predicts the generation of citrullinated proteins in the lesion. Citrullination of proteins may lead to the formation of anti-citrullinated autoantibodies (ACPA-s) initiating the formation of an autoimmune loop which may contribute to the perpetuation of inflammatory reactions and tissue damage in chronic apical periodontitis. The objective of this study was to demonstrate the formation of citrullinated proteins in chronic apical periodontitis and whether they can act as autoantigens. METHODOLOGY: Twenty-five periapical granulomas (n = 25) were investigated in the study. Healthy periodontal tissue samples served as normal control tissue (n = 6). The peptidyl-citrulline level was determined with the dot blot method. ACPA levels were analysed using anti-citrullinated cyclic peptide (anti-CCP) EDIA kit. Differences between periapical granuloma and control samples were assessed using Mann-Whitney U tests. p Values <.05 were considered as statistically significant. RESULTS: Protein concentrations, peptidyl-citrulline levels and anti-CCP ratios were compared between periapical granuloma and healthy control groups. Multiple linear regression analysis revealed significant (p = .042) hypercitrullination in periapical granuloma samples. Moreover, there was a significant difference in the ACPA ratios between periapical granuloma (2.03 ± 0.30) and healthy control (0.63 ± 0.17) groups (p = .01). Seventeen of 25 periapical granuloma samples (17/25; 68%), whereas one out of six control samples (1/6; 17%) were shown to be positive for the presence of ACPA. CONCLUSIONS: This is the first study detecting the presence of citrullinated peptides and APCA in periapical granuloma, suggesting the contribution of autoimmune reactions in the pathogenesis and perpetuation of chronic apical periodontitis.

Disease Activity Is Associated with Obesity in Newly Diagnosed Pediatric Patients with Ulcerative Colitis.

Malnutrition and inflammatory bowel disease (IBD) are interrelated conditions. Our aim was to assess the prevalence of malnutrition, to compare anthropometric parameters in the evaluation of nutritional status in pediatric IBD, and to investigate the association between anthropometric parameters and disease activity indices (AI). Pediatric patients with newly diagnosed IBD recorded between 2010 and 2016 in the Hungarian Pediatric IBD Registry were included in this cross-sectional study. Body weight, body mass index (BMI), weight-for-height, and ideal body weight percent (IBW%) were analyzed. Pearson linear and non-linear correlations and polynomial regression analyses were performed to assess correlation between nutritional status and AI. p-values < 0.05 were considered significant. Anthropometric data of 1027 children with IBD (Crohn's disease (CD): 699; ulcerative colitis (UC): 328; mean age 13.7 years) were analyzed. IBW% identified more obese patients than BMI both in CD (7.02% vs. 2.28%) and UC (12.17% vs. 5.48%). Significant negative correlation was found among anthropometric parameters and AI in CD. In contrast, polynomial regression analysis revealed a U-shaped correlation curve between IBW% and AI in UC. Our findings show that obesity has a bimodal association with disease activity in pediatric UC. Furthermore, IBW% was more useful to identify obese pediatric patients with IBD.

The role of urinary N-acetyl-ß-D-glucosaminidase in early detection of acute kidney injury among pediatric patients with neoplastic disorders in a retrospective study.

BACKGROUND: The 1-year cumulative incidence of AKI reportedly is high (52%) in pediatric neoplastic disorders. About half of these events occur within 2 weeks. However, subclinical AKI episodes may remain unrecognized by the conventional creatinine-based approaches. We investigated the diagnostic value of urinary N-acetyl-ß-D-glucosaminidase (uNAG) as an early marker of acute kidney injury (AKI). METHODS: In our retrospective study, 33 children with neoplastic disorders were inculded who had serial uNAG tests (at least 5 samples/patient) with a total of 367 uNAG measurements. Renal function was determined by cystatin-C and creatinine based GFR, and relative increase of uNAG index (uNAGRI). We focused on detecting both clinical and subclinical AKI episodes (according to Biomarker-Guided Risk Assessment using pRIFLE criteria and /or elevated uNAG levels) and the incidence of chronic kidney damage. RESULTS: Sixty episodes in 26 patients, with positivity at least in one parameter of kidney panel, were identified during the observation period. We detected 18/60 clinical and 12/60 subclinical renal episodes. In 27/60 episodes only uNAG values was elevated with no therapeutic consequence at presentation. Two patients were detected with decreased initial creatinine levels with 3 "silent" AKI. In 13 patients, modest elevation of uNAG persisted suggesting mild, reversible tubular damage, while chronic tubuloglomerular injury occurred in 5 patients. Based on ROC analysis for the occurence of AKI, uNAGRI significantly indicated the presence of AKI, the sensitivity and specificity are higher than the changes of GFRCreat. Serial uNAG measurements are recommended for  the reduction of the great amount of false positive uNAG results, often due to overhydratation. CONCLUSION: Use of Biomarker-guided Risk Assessment for AKI identified 1.5 × more clinical and subclinical AKI episodes than with creatinine alone in our pediatric cancer patients. Based on the ROC curve for the occurence of AKI, uNAGRI has relatively high sensitivity and specificity comparable to changes of GFRCysC. The advantage of serial uNAG measurements is to decrease the number of false positive results. TRIAL REGISTRATION: The consent to participate is not applicable because it was not reqired for ethical approval and it is a retrospectiv study.

Case Report: A Child With Hemophilia A Serves as Donor for Hematopoietic Stem Cell Transplantation to Cure His Brother's Severe Aplastic Anemia.

The first-line treatment of severe aplastic anemia is allogeneic hematopoietic stem cell transplantation with a matched sibling donor. However, co-morbidities of the identical donor can make donation difficult. We present a transplantation where in parallel with the patient's conditioning treatment, the preparation of the donor with severe hemophilia A required a special management with perioperative factor VIII substitution. Donation was successful without complications, and 18 months after transplantation, the patient and his donor are well without any long-term sequelae. To our knowledge, this is the first reported succesfull transplantation with hemophilic child serving as a bone marrow donor. The procedure did not mean a significant risk to donor health, so donors with hemophilia should not be excluded from donation.

Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in Primary Human Endometrial Carcinomas: Novel Therapeutic Approaches.

Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various tumors, including endometrial carcinomas (EC). However, tumoral receptors that mediate the antiproliferative effects of GHRH antagonists in human ECs have not been fully characterized. In this study, we investigated the expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors (GHRH-R) in 39 human ECs and in 7 normal endometrial tissue samples using RT-PCR. Primers designed for the PCR amplification of mRNA for the full length GHRH-R and SVs were utilized. The PCR products were sequenced, and their specificity was confirmed. Nine ECs cancers (23%) expressed mRNA for SV1, three (7.7%) showed SV2 and eight (20.5%) revealed mRNA for SV4. The presence of SVs for GHRH-Rs could not be detected in any of the normal endometrial tissue specimens. The presence of specific, high affinity GHRH-Rs was also demonstrated in EC specimens using radioligand binding studies. Twenty-four of the investigated thirty-nine tumor samples (61.5%) and three of the seven corresponding normal endometrial tissues (42.9%) expressed mRNA for GHRH ligand. Our findings suggest the possible existence of an autocrine loop in EC based on GHRH and its tumoral SV receptors. The antiproliferative effects of GHRH antagonists on EC are likely to be exerted in part by the local SVs and GHRH system.

Clinical Course of COVID-19 Disease in Children Treated With Neoplastic Diseases in Hungary.

We report on children with cancer in Hungary suffering from COVID-19, surveying a 13-months-long period of time. We performed a retrospective clinical trial studying the medical documentation of children treated in seven centers of the Hungarian Pediatric Oncology-Hematology Group. About 10% of children admitted to tertiary hemato-oncological centers for anti-neoplastic treatment or diagnosis for de novo malignancies were positive for SARS-CoV-2 infection. Nearly two-thirds of the infected patients were asymptomatic or had only mild symptoms but showed seropositivity by 1-4.5 months after positive PCR. One third of the SARS-CoV-2-positive children were hospitalized due to symptomatic COVID-19. Five children required antiviral treatment with remdesivir. One child was referred to the intensive care unit, requiring intubation and mechanical ventilation. Delay in the scheduled anti-cancer treatment did not exceed 2 weeks in the majority (89%) of cases. There was only one patient requiring treatment deferral longer than a month. There was no COVID-19-related death in patients under 18 years of age, and nor was multisystem inflammatory syndrome diagnosed. In conclusion, SARS-CoV-2 infection did not represent an untoward risk factor among children with cancer in Hungary.

Salivary miR-31-5p, miR-345-3p, and miR-424-3p Are Reliable Biomarkers in Patients with Oral Squamous Cell Carcinoma.

If not detected early, oral squamous cell carcinoma (OSCC) has very poor prognosis, emphasizing the need for reliable early diagnostics. Saliva is considered a promising surrogate biosample for OSCC detection, because it comes into contact with many cells of the tumor mass, providing a comprehensive sampling of tumor-specific biomolecules. Although several protein- and RNA-based salivary biomarkers have been proposed for the detection of OSCC, the results of the studies show large differences. Our goal was to clarify which salivary microRNAs (miRNA) show reliably high expression in the saliva of OSCC patients, to be used as cancer-specific biomarkers, and potentially as early diagnostic biomarkers. Based on a detailed literature search, we selected six miRNAs commonly overexpressed in OSCC, and analyzed their expression in saliva samples of cancer patients and controls by real-time quantitative PCR. Our results suggest that miR-345 and miR-31-5p are consistently upregulated salivary biomarkers for OSCC, and a three-miRNA panel of miR-345, miR-31-5p, and miR-424-3p can distinguish cancer and control patients with high sensitivity.

Remission, treatment failure, and relapse in pediatric ALL: an international consensus of the Ponte-di-Legno Consortium.

Comparison of treatment strategies in de novo pediatric acute lymphoblastic leukemia (ALL) requires standardized measures of efficacy. Key parameters that define disease-related events, including complete remission (CR), treatment failure (TF; not achieving CR), and relapse (loss of CR) require an updated consensus incorporating modern diagnostics. We collected the definitions of CR, TF, and relapse from recent and current pediatric clinical trials for the treatment of ALL, including the key components of response evaluation (timing, anatomic sites, detection methods, and thresholds) and found significant heterogeneity, most notably in the definition of TF. Representatives of the major international ALL clinical trial groups convened to establish consensus definitions. CR should be defined at a time point no earlier than at the end of induction and should include the reduction of blasts below a specific threshold in bone marrow and extramedullary sites, incorporating minimal residual disease (MRD) techniques for marrow evaluations. TF should be defined as failure to achieve CR by a prespecified time point in therapy. Relapse can only be defined in patients who have achieved CR and must include a specific threshold of leukemic cells in the bone marrow confirmed by MRD, the detection of central nervous system leukemia, or documentation of extramedullary disease. Definitions of TF and relapse should harmonize with eligibility criteria for clinical trials in relapsed/refractory ALL. These consensus definitions will enhance the ability to compare outcomes across pediatric ALL trials and facilitate development of future international collaborative trials.

A Novel Method for the Evaluation of Bone Marrow Samples from Patients with Pediatric B-Cell Acute Lymphoblastic Leukemia-Multidimensional Flow Cytometry.

Multicolor flow cytometry (FC) evaluation has a key role in the diagnosis and prognostic stratification of ALL. Our aim was to create new analyzing protocols using multidimensional dot-plots. Seventy-two pediatric patients with ALL were included in this single-center study. Data of a normal BM sample and three BM samples of patients with BCP-ALL were merged, then all B cell populations of the four samples were presented in a single radar dot-plot, and those parameters and locations were selected in which the normal and pathological cell populations differed from each other the most. The integrated profile of immunophenotype resulted in a simple, rapid, and accurate method. There were no significant differences between the percentages of lymphoblasts in the detection of minimal residual disease (MRD) by multidimensional or conventional FC method (p = 0.903 at Day 15 and p = 0.155 at Day 33). Furthermore, we found associations between the position and the number of clusters of blast cells in the radar plots and cytogenetic properties (p = 0.002 and p < 0.0001 by the position and p = 0.02 by the number of subclones). FC analysis based on multidimensional dot-plots is not only a rapid, easy-to-use method, but can also provide additional information to screen cases which require detailed genetic examination.

Recent Advances in the Management of Pediatric Acute Myeloid Leukemia-Report of the Hungarian Pediatric Oncology-Hematology Group.

Outcome measures of pediatric acute myeloid leukemia (AML) improved considerably between 1990 and 2011 in Hungary. Since 2012, efforts of the Hungarian Pediatric Oncology-Hematology Group (HPOG) included the reduction in the number of treatment centers, contemporary diagnostic procedures, vigorous supportation, enhanced access to hematopoietic stem cell transplantation (HSCT), and to targeted therapies. The major aim of our study was to evaluate AML treatment results of HPOG between 2012 and 2019 with 92 new patients registered (52 males, 40 females, mean age 7.28 years). Two periods were distinguished: 2012-2015 and 2016-2019 (55 and 37 patients, respectively). During these periods, 2 y OS increased from 63.6% to 71.4% (p = 0.057), and the 2 y EFS increased significantly from 56.4% to 68.9% (p = 0.02). HSCT was performed in 37 patients (5 patients received a second HSCT). We demonstrate advances in the diagnosis and treatment of acute promyelocytic leukemia (APL) in two cases. Early diagnosis and follow-up were achieved by multidimensional flow cytometry and advanced molecular methods. Both patients were successfully treated with all-trans retinoic acid and arsenic-trioxide, in addition to chemotherapy. In order to meet international standards of pediatric AML management, HPOG will further centralize treatment centers and diagnostic facilities and join efforts with international study groups.

A Cross-National Survey of People Living with Hemophilia: Impact on Daily Living and Patient Education in Central Europe.

BACKGROUND: Information about the impact of hemophilia on daily living and information preferences for patients and their caregivers in Central Europe has been limited. METHODS: This cross-national survey was conducted between April 1 and October 15, 2020 and utilized a self-administered questionnaire to collect data (Typeform™) from people living with hemophilia in Bulgaria, Croatia, Czech Republic, Hungary, Slovakia and Slovenia. The questionnaire included 22 questions regarding difficulties in daily life and preferences for receiving hemophilia-related information. Respondents were stratified into two main groups, people with hemophilia (PwH) or their caregivers (CPwH). Results were analyzed using descriptive statistics. RESULTS: Of the 364 respondents, 232 were PwH (63.7%) and 132 were CPwH (36.3%). In total, 70.3% of hemophilia patients/caregivers responded that they are kept sufficiently informed about life with hemophilia, with 68.0%, 59.1% and 56.3% of respondents obtaining information from their physicians, patient associations and via digital media (internet and social media), respectively. However, 97.8% of respondents expressed an interest in additional information, particularly new hemophilia treatment options (62.1%), which in contrast to other topics was indicated most frequently by both patients and caregivers in all six countries. Most frequent difficulties in everyday life with hemophilia were identified as mobility problems (41.8%), unexpected bleeding (38.5%), pain (35.4%), and uncertainty with what they can or cannot do (25.0%). During the 2020 COVID-19 pandemic, 52.5% of respondents reported that they did not experience any major change in daily living with hemophilia. CONCLUSION: Based on our Central European survey, hemophilia mostly affects peoples' lives by causing mobility difficulties, unexpected bleeding, pain and uncertainty in daily activities. Although the majority of respondents reported being educated about hemophilia, most PwH and CPwH respondents sought additional information, highlighting the need for continuous personalized patient education to cope with present challenges.