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Background: A personalised approach to the treatment of acute myeloid leukemia (AML) in children and adolescents, as well as the development of supportive therapies, has significantly improved survival. Despite this, some patients still die before starting treatment or in an early phase of therapy before achieving remission. The study analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment related deaths (TRD) of children and adolescents with AML., Methods: From January 2005 to November 2023, 646 children with AML treated in the centers of the Polish Pediatric Leukemia and Lymphoma Study Group according to three subsequent therapeutic protocols were evaluated: AML-BFM 2004 Interim (385 children), AML-BFM 2012 Registry (131 children) and AML-BFM 2019 (130 children)., Results: Out of 646 children, early death occurred in 30 children, including 15 girls. The median age was 10.7 years (1 day to 18 years). More than half of the patients (53%) were diagnosed with acute myelomonocytic leukemia (M5) and 13% with acute promyelocytic leukemia (M3). The ED rate for the three consecutive AML-BFM protocols was 4.9% vs. 5.3% vs. 3.1%, respectively. In 19 patients, death occurred before the 15th day of treatment, in 11 between the 15th and 42nd day. The most common cause of death before the 15th day (ED15) was leukostasis and bleeding, whereas between the 15th and 42nd day (ED15-42), infections, mainly bacterial sepsis. A significant association was found between ED15 and high leukocyte count (>10 × 10 9 /L), M3 leukemia ( p  < 0.001), and ED15-42 and age <1 year ( p  = 0.029). In the univariate analysis only initial high leukocyte count >100 × 10 9 /L, was a significant predictor of early death. The overall TRD for the entire study period was 3.4%. The main cause of death were infections, mainly bacterial sepsis (10 children out of 22, 45.4%)., Conclusions: Hyperleukocytosis remains significant factor of early mortality in patients with AML, despite the introduction of various cytoreductive methods. Infections are still the main cause of treatment related deaths. A more individualized approach by using new targeted drugs may be the therapeutic option of choice in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Pawińska-Wąsikowska, Czogała, Bukowska-Strakova, Surman, Rygielska, Książek, Sadowska, Pac, Skalska-Sadowska, Samborska, Wachowiak, Ciebiera, Chaber, Tomaszewska, Szczepański, Zielezińska, Urasiński, Rodziewicz-Konarska, Kałwak, Kozłowska, Irga-jaworska, Sikorska-Fic, Chyżyński, Łaguna, Muszyńska-Rosłan, Krawczuk-Rybak, Deleszkiewicz, Drabko, Bobeff, Młynarski, Chodała-Grzywacz, Karolczyk, Mycko, Badowska, Bartoszewicz, Styczyński, Machnik, Stolpa, Mizia-Malarz, Balwierz and Skoczeń.)

Purpose: This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL., Methods: The study group included 2303 children receiving intensive chemotherapy for ALL. The group was divided into patients with at least one episode of AP and those who did not develop AP after treatment for ALL., Results: The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for the development of AP (OR = 1.05; 95%CI = 1.006-1.098; p = 0.03). The overall mortality associated with AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) in both subgroups were 0.84 vs. 0.86, log-rank p = 0.65 and 0.75 vs. 0.80, log-rank p = 0.12, respectively. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent treatment phases. Only one patient re-exposed to ASP (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p = 0.27 and 0.63 vs. 0.79, log-rank p = 0.09, respectively)., Conclusions: The incidence of AP in children with ALL is low and related to patients' age. The development of AP does not seem to influence p-DFS and p-EFS in children with ALL. Recurrence of AP after re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP does not improve either p-DFS or p-EFS in children with ALL.

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.

"Managing Undernutrition in Pediatric Oncology" is a collaborative consensus statement of the Polish Society for Clinical Nutrition of Children and the Polish Society of Pediatric Oncology and Hematology. The early identification and accurate management of malnutrition in children receiving anticancer treatment are crucial components to integrate into comprehensive medical care. Given the scarcity of high-quality literature on this topic, a consensus statement process was chosen over other approaches, such as guidelines, to provide comprehensive recommendations. Nevertheless, an extensive literature review using the PubMed database was conducted. The following terms, namely pediatric, childhood, cancer, pediatric oncology, malnutrition, undernutrition, refeeding syndrome, nutritional support, and nutrition, were used. The consensus was reached through the Delphi method. Comprehensive recommendations aim to identify malnutrition early in children with cancer and optimize nutritional interventions in this group. The statement underscores the importance of baseline and ongoing assessments of nutritional status and the identification of the risk factors for malnutrition development, and it presents tools that can be used to achieve these goals. This consensus statement establishes a standardized approach to nutritional support, aiming to optimize outcomes in pediatric cancer patients.

Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld ® ) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study's non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.

Background: The reports of studies that compare the survival of adolescents and young adults with younger children with acute myeloid leukemia (AML) are contradictory., Patients and Methods: We retrospectively analyzed 220 AML patients aged 0-18 years treated in pediatric oncologic centers in Poland from 2015 to 2022. The evaluated group included 31 infants (below 1 year), 91 younger children (1-9.9 years), 59 older children (10-14.9 years), and 39 adolescents (15-18 years)., Results: A 5-year overall survival for adolescents was not significantly inferior compared to younger and older children (74.3 ± 7.6% vs. 80.5 ± 4.4% vs. 77.9 ± 5.1, p = 0.243). However, relapse-free survival was lower in adolescents compared to younger children (76.5 ± 7.8% vs. 65.7 ± 9.0%, p = 0.049), and treatment-related mortality tended to be higher (10.3% vs. 4.4%, p = 0.569). In the univariate analysis, high-risk genetics [HR, 2.0 (95% CI 1.1-3.6; p = 0.014)] and a leukocyte count at diagnosis above 100,000/μL [HR, 2.4 (95% CI 1.3-4.6; p = 0.004)] were found to be unfavorable prognostic factors for survival., Conclusions: Although we have not found that age over 15 years is an unfavorable factor for overall survival, the optimal approach to therapy in adolescents, as in other age groups, is to adjust the intensity of therapy to individual genetic risk and introduce targeted therapies when indicated.

Background/aim: The role of immune checkpoint inhibitors (ICIs; anti-PD1) in the treatment of childhood cancers is still evolving. The aim of this nationwide retrospective study was to assess the safety and effectiveness of ICIs used in a group of 42 patients, with a median age of 13.6 years, with various types of advanced malignancies treated in pediatric oncology centers in Poland between 2015 and 2023., Results: The indications for treatment with anti-PD1 were as follows: Hodgkin lymphoma (11); malignant skin melanoma (9); neuroblastoma (8); and other malignancies (14). At the end of follow-up, complete remission (CR) was observed in 37.7% (15/42) of children and disease stabilization in 9.5% (4/42), with a mean survival 3.6 (95% CI = 2.6-4.6) years. The best survival (OS = 1.0) was observed in the group of patients with Hodgkin lymphoma. For malignant melanoma of the skin, neuroblastoma, and other rare malignancies, the estimated 3-year OS values were, respectively, 0.78, 0.33, and 0.25 ( p = 0.002). The best progression-free survival value (0.78) was observed in the group with malignant melanoma. Significantly better effects of immunotherapy were confirmed in patients ≥ 14 years of age and good overall performance ECOG status. Severe adverse events were observed in 30.9% (13/42) patients.

Background: Gemtuzumab ozogamicin (GO), one of the first targeted drugs used in oncology, consists of an anti-cluster of differentiation 33 (CD33) monoclonal antibody bound to a derivative of cytotoxic calicheamicin. After the drug withdrawn in 2010 due to a significantly higher rate of early deaths, GO regained approval in 2017 for the treatment of newly diagnosed, refractory, or relapsed acute myeloid leukemia (AML) in adults and children over 15 years of age. The objective of the study was a retrospective analysis of clinical characteristics, treatment outcomes, and GO toxicity profile in children with primary refractory or relapsed (R/R) AML treated in Poland from 2008 to 2022., Methods: Data were collected through the Polish Registry of Acute Myeloid Leukemia. From January 2008 to December 2022, 35 children with R/R AML were treated with GO in seven centers of the Polish Pediatric Leukemia and Lymphoma Study Group., Results: Most of the children (30 of 35) received only one GO cycle in combination with various chemotherapy cycles (IDA-FLA, DOXO-FLA, FLA, FLAG, and others). Eighteen children (51%) achieved complete remission (CR), 14 did not respond to treatment, and three progressed. GO therapy was followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 18 children in CR. The 5-year overall survival (OS) after GO therapy was 37.1% ± 8.7% for the total cohort. There was a trend toward a superior outcome in patients with strong expression of CD33 expression (over 50% positive cells) compared with that in patients with lower expression of CD33 (OS, 41.2% ± 11.9% versus 27.8% ± 13.2%; p = 0.5; 5-year event-free survival, 35.4% ± 11.6% versus 25.7% ± 12.3%; p = 0.5, respectively). Children under 15 years have better outcome (OS, 34.9% ± 10.4% versus 30% ± 14.5%, p = 0.3). The most common adverse events were bone marrow aplasia, fever of unknown origin, infections, and elevated liver enzyme elevation. Sinusoidal obstruction syndrome occurred in two children., Conclusions: The use of GO in severely pretreated children, including those under 15 years of age, with previous failure of AML treatment is a feasible and effective bridging therapy to allo-HSCT with an acceptable toxicity profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Pawinska-Wasikowska, Czogala, Skoczen, Surman, Rygielska, Ksiazek, Pac, Wieczorek, Skalska-Sadowska, Samborska, Wachowiak, Chaber, Tomaszewska, Szczepanski, Zielezinska, Urasinski, Moj-Hackemer, Kalwak, Kozlowska, Irga-Jaworska, Balwierz and Bukowska-Strakova.)

The most common complications related to the treatment of childhood acute lymphoblastic leukemia (ALL) are infections. The aim of the study was to analyze the incidence and mortality rates among pediatric patients with ALL who were treated in 17 Polish pediatric hematology centers in 2020-2021 during the pandemic. Additionally, we compared these results with those of our previous study, which we conducted in the years 2012-2017. The retrospective analysis included 460 patients aged 1-18 years with newly diagnosed ALL. In our study, 361/460 (78.5%) children were reported to have microbiologically documented bacterial infections during chemotherapy. Ten patients (2.8%) died due to sepsis. Fungal infections were reported in 99 children (21.5%), of whom five (5.1%) died due to the infection. We especially observed an increase in bacterial infections during the pandemic period compared to the previous study. The directions of our actions should be to consider antibiotic prophylaxis, shorten the duration of hospitalization, and educate parents and medical staff about complications (mainly infections) during anticancer therapy. It is necessary to continue clinical studies evaluating infection prophylaxis to improve outcomes in childhood ALL patients., (© 2023. The Author(s).)

Magnetic Resonance Imaging (MRI) plays a leading role in diagnosing soft tissue pathologies, especially in the head and neck. It is increasingly popular for evaluating salivary gland issues like neoplasms and Sjogren's Syndrome. Advanced MRI methods, including MRI sialography and texture analysis, offer non-invasive alternatives, enhancing MRI's role. This study focused on the relationship between the apparent diffusion coefficient (ADC) and T2-weighted MRI sialography and texture analysis (TA) of parotid glands in children with and without Sjogren's Syndrome (SS). Using 3.0 Tesla MRI with DWI and T2-weighted imaging, expended texture analysis, first-order statistics (FSOs), second-order, and higher-order statistics were conducted. The results showed significant differences in parotid ADC values, with lower values in the SS group, particularly in cases of higher disease activity. Lower kurtosis values were associated with more severe Tonami Scale grades. FSO parameters correlated well with the texture analysis from T2-weighted images, indicating promise in grading parotid gland inflammation. However, further research is needed to understand the impact of variables like binning and region of interest (ROI) size. This study highlights the potential of texture analysis for assessing parotid gland inflammation and emphasizes the need for more investigations in this area.

To a large extent, the clinical picture of pediatric mastocytosis depends on the age at which it is diagnosed. A neonate with diffuse cutaneous mastocytosis may frequently present in a severe state requiring treatment. Toddlers may require long-term anti-mediator therapy, and this may lead to concerns such as organizing preschool education due to the need for epinephrine injections. A teenager may have to face cutaneous disease persistence or a diagnosis of systemic mastocytosis. Further studies are needed to refine the available treatment options and prognosis for different age groups., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The FMS-like tyrosine kinase 3 (FLT3) gene mutated in 10-15% of pediatric acute myeloid leukemia (AML) is associated with an inferior outcome. The aim of the study was to analyze the outcome and characteristics of FLT3-ITD-positive pediatric AML., Methods: We retrospectively analyzed the nationwide pediatric AML database from between 2005 and 2022. FLT3-ITD was found in 54/497 (10.7%) patients with available analysis. Three consecutive treatment protocols were used (AML-BFM 2004 Interim, AML-BFM 2012 Registry, AML-BFM 2019 recommendations)., Results: Probabilities of 5-year overall (OS), event-free (EFS) and relapse-free survival were significantly lower in the FLT3-ITD-positive patients compared to FLT3-ITD-negative (0.54 vs. 0.71, p = 0.041; 0.36 vs. 0.59, p = 0.0004; 0.47 vs. 0.70, p = 0.0029, accordingly). An improvement in the outcome was found in the analyzed period of time, with a trend of better survival in patients treated under the AML-BFM 2012 and AML-BFM 2019 protocols compared to the AML-BFM 2004 protocol (5-year EFS 0.52 vs. 0.27, p = 0.069). There was a trend of improved outcomes in patients treated with FLT3 inhibitors (n = 9, 2-year EFS 0.67 vs. 0.33, p = 0.053) and those who received stem cell transplantation (SCT) (n = 26; 5-year EFS 0.70 vs. 0.27, p = 0.059). The co-occurrence of the WT1 mutation had a dismal impact on the prognosis (5-year EFS 0.23 vs. 0.69, p = 0.002), while the NPM1 mutation improved survival (5-year OS 1.0 vs. 0.44, p = 0.036)., Conclusions: It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.

Background: The survivors of childhood cancer suffer from a number of long-term side effects. These include atherosclerosis and cardiovascular diseases (CVDs) that develop earlier in adulthood than in the rest of the population. The aim of this study was to identify prognostic factors of developing atherosclerosis before the development of symptomatic CVD., Methods: A total of 141 children that were 7-18 years old were examined; there were 116 survivors of childhood malignancies (hematopoietic and lymphoproliferative malignancies-52; neuroblastoma-22; Wilms tumor-24; other solid tumors-18) and 25 healthy controls. Anthropometric measurements, blood pressure measurements, ultrasonography of the abdomen, echocardiography, and laboratory tests were performed., Results: There were no significant differences in gender distribution, time from the end of the treatment, weight, BMI, prevalence of central obesity, blood pressure and resistive index of the renal arteries, lipid profile, or glucose and fibrinogen levels. Patients with solid tumors had a significantly lower height and worse renal function. Patients with hematological malignancies significantly presented the lowest shortening fraction of the left ventricle. The salusin β levels were significantly higher in the control group than among the patients., Conclusions: The type and severity of side effects are closely related to the type of neoplasm and the treatment that has been undergone. Careful observation and regular follow-up are necessary.

Background and Objectives: The primary objective of the undertaken study was to determine the morphological changes that occur within the oral epithelium in children undergoing chemotherapy following a diagnosis of hematological malignancies., Materials and Methods: The study group consisted of 18 patients diagnosed with leukemia or lymphoma undergoing treatment with chemotherapy. Swabs (liquid-based cytology) were collected from the oral cavity for microscopic evaluation at baseline, during the chemotherapy cycle with oral mucositis symptoms present, and upon completion of the cycle. Both the neutrophil count and oral mucositis (OM) were registered using the WHO (World Health Organization) scale. The control group included 41 children who were generally healthy. All samples underwent microscopical analyses at the Department of Pathology, Medical University of Gdansk, Poland., Results: A total of 190 cytological preparations were evaluated. The baseline preparations revealed similar cytological images, and the superficial cells of the epithelial layers were seen. A significant ( p < 0.01) increase in the number of cells in the intermediate layer of the oral epithelium, as well as a decrease ( p < 0.01) in the volume of cells in the superficial layers, was observed in further stages of cytostatic treatment., Conclusions: A decrease in the percentage of superficial epithelial cells with a corresponding increase in the number of intermediate epithelial cells is considered to be a result of toxic damage to the oral mucosa during chemotherapy.

The impact of past COVID-19 infection on the immune system remains unidentified. So far, several papers have revealed the dependence between the count of lymphocytes and their subsets and the outcome of an acute disease. However, still there is little information about long-term consequences, particularly in the pediatric population. We attempted to verify whether a dysregulation of the immune system may be the reason for observed complications after past COVID-19 infection. Hence, we tried to prove that abnormalities in lymphocyte subpopulations are found in patients a certain time after the COVID-19 infection. In our paper, we enrolled 466 patients after SARS-CoV-2 infection, and evaluated their subsets of lymphocytes within 2-12 months after infection and compared them to the control group assessed several years before the pandemic. It occurred that main differences are observed in CD19 + lymphocytes and the index CD4 + /CD8 + lymphocytes. We believe that this is only the introduction to further investigation of the immune system of pediatric patients post-COVID-19 infection.

Acute P./myeloid leukemia post cytotoxic therapy (AML-pCT) is rare complication of cancer treatment in childhood. The objective of the study was to identify clinical characteristics and provide an analysis of the outcomes in pediatric AML-pCT. We retrospectively analyzed the data of 40 children with AML-pCT, treated from 2005 to 2020 within the Polish Pediatric Leukemia and Lymphoma Study Group. The most common primary malignancies were acute lymphoblastic leukemia (32.5%) and brain tumors (20%). The median latency period was 2.9 years (range: 0.7-12.9). Probabilities of overall (OS), event-free (EFS), and relapse-free survival (RFS) in the whole cohort were 0.49 ± 0.08, 0.43 ± 0.08, and 0.64 ± 0.10, respectively. Significant improvements in outcomes were observed in patients treated from 2015-2022 (two induction cycles followed by stem cell transplantation-SCT in 69% of patients) compared to 2005-2014 (four induction cycles followed by SCT in 49% of patients). The probability of EFS increased from 0.30 ± 0.10 to 0.67 ± 0.12 ( p = 0.07) and RFS increased from 0.46 ± 0.11 to 1.0 ( p = 0.01). The poorest outcome (OS and EFS 0.25 ± 0.20) was in AML post brain tumor, mainly due to deaths from toxicities. To conclude, treatment results achieved in patients with AML-pCT treated from 2015-2022, with two induction cycles followed by immediate SCT, were better than those reported by other authors, and comparable to the results in de novo AML.

Introduction: This study aimed to present the clinical features and results of treatment of patients diagnosed with refractory or relapsed acute myeloid leukaemia (AML) in Polish Paediatric Leukaemia/Lymphoma Study Group (PPL/LSG) institutions, treated in accordance with the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012, as their first-line therapy., Material and Methods: The outcome data of 10 patients with refractory AML (median age 9.5 years) and 30 with relapsed AML (median age 12 years) were analysed retrospectively. Re-induction was usually based on idarubicin, fludarabine, and cytarabine along with allogeneic haematopoietic stem cell transplant (allo-HSCT) in 5 patients with refractory AML and 7 relapsed AML children., Results: 37.5% (3/8) of refractory AML patients achieved second complete remission second complete remission (CRII). One of ten patients (1/10; 10%) was alive and stayed in complete remission for 34 months after the allo-HSCT. The probability of 3-year event-free survival (pEFS) in this group was 0.125 ±0.11. In the group of relapsed AML patients, the CRII was achieved in 9 patients (34%), and the probability of survival was: pEFS = 0.24 ±0.08; probability overall survival (pOS) = 0.34 ±0.09, with significantly better results achieved in patients who underwent allo-HSCT (pOS = 0.54 ±0.14 vs. 0.08 ±0.08, p < 0.0001)., Conclusions: The prognosis of refractory AML and the first AML recurrence in children who were first-line treated in PPL/LSG centres according to Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 is poor. Failures of re-induction treatment particularly result from difficulties in achieving remission. Allogeneic HSCT improves prognosis in children with refractory and first recurrent AML, under the condition it is performed in complete remission. Novel therapeutic approaches are needed to increase the remission rate and improve the outcomes., Competing Interests: The author declares no conflict of interest., (Copyright © 2023 Termedia.)

Background: Vitamin D deficiency is ubiquitous within the population of children. A similar problem is recognized among pediatric patients with acute lymphoblastic leukemia. The purpose of this study was to analyze the prevalence of vitamin D deficiency and to investigate the connection between vitamin D status and the course of induction treatment of ALL., Materials and Methods: A cross-sectional study including 59 patients with newly diagnosed ALL from May 2017 until November 2020., Results: Vitamin D deficiency was found in 39% of the patients. There were no seasonal differences in vitamin D status. Patients with optimal 25(OH)D concentration presented more profound thrombocytopenia ( P =0.015) and required more frequent platelet transfusions ( P =0.018). Good prognosis factors such as B phenotype and hyperdiploidy were also more frequent among children with higher 25(OH)D concentration ( P =0.01 and 0.014, respectively)., Conclusions: The study showed that patients with a higher serum concentration of 25(OH)D presented deeper thrombocytopenia and needed more frequent transfusions. Moreover, those patients showed higher rates of B-cell leukemia and hyperdiploid karyotype. We did not find any influence of the possible exposure to sunlight (defined as the season of the year on admission) on serum 25(OH)D concentration, which supports the argument for supplementing vitamin D all year round. Moreover, the supplementing of vitamin D seems to be safe and does not cause any renal complications connected to calcium and phosphorus imbalance as no correlation between their levels and 25(OH)D concentration was found., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Stroke remains one of the greatest health challenges worldwide, due to a high mortality rate and, despite great progress in its treatment, the significant disability that it causes. Studies conducted around the world show that the diagnosis of stroke in children is often significantly delayed. Paediatric ischaemic arterial stroke (PAIS) is not only a problem that varies greatly in frequency compared to the adult population, it is also completely different in terms of its risk factors, clinical course and outcome. The main reason for the lack of a rapid diagnosis of PAIS is a lack of access to neuroimaging under general anaesthesia. The insufficient knowledge regarding PAIS in society as a whole is also of great importance. Parents and carers of children should always bear in mind that paediatric age is not a factor that excludes a diagnosis of stroke. The aim of this article was to develop recommendations for the management of children with acute neurological symptoms suspected of ischaemic stroke and further treatment after confirmation of the ischaemic aetiology of the problem. These recommendations are based on current global recommendations for the management of children with stroke, but our goal was also to match them as closely as possible to the needs and technical diagnostic and therapeutic possibilities encountered in Poland. Due to the multifactorial problem of stroke in children, not only paediatric neurologists but also a neurologist, a paediatric cardiologist, a paediatric haematologist and a radiologist took part in the preparation of these recommendations.

Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk molecular subtype with a gene expression profile similar to Philadelphia-positive ALL, but not harboring the BCR-ABL1 gene fusion. We aimed to investigate the efficacy of target therapy with the Janus kinase inhibitor, ruxolitinib, in patients with Ph-like ALL and molecular signature of JAK-STAT signaling pathway. A systematic search of the literature was performed to identify reports concerning administration of ruxolitinib in Ph-like ALL patients. Additionally, Polish Pediatric ALL registries were searched for patients with Ph-like ALL treated with ruxolitinib. Extracted information included epidemiological background, somatic aberrations, treatment response, and patient outcome. After PubMed database search, twelve patients were identified, and one was identified in the Polish Pediatric ALL registry. In nine patients gene fusions affecting JAK2 (n = 7) and EPOR (n = 2) were detected. Surface overexpression of CRLF2 and IKZF1 deletions were observed in two and three patients, respectively. Induction failure occurred in all the patients. Therapy with ruxolitinib led to complete (n = 7) and partial (n = 2) remission, in three individuals no information was found. Based on the limited number of studies describing the efficacy of ruxolitinib as an additional compound administrated with standard ALL therapy, we conclude that this approach can be considered in patients with aberrations activating JAK-STAT pathway., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Infections caused by Stenotrophomonas maltophilia (SM) have documented high mortality rate in immunocompromised patients., Aim: This nationwide multicenter study was performed to analyze the epidemiology of SM infections in children undergoing anticancer therapy (pediatric hematology and oncology [PHO]) or hematopoietic cell transplantation (HCT) over 2012-2019, including incidence and outcome of SM infections, as well as treatment regimens and multidrug resistance., Methods: Cumulative incidence of SM infections was calculated using the competing risk analysis from the day of diagnosis (PHO setting) or from the day of transplantation (HCT setting). The Kaplan-Meier method was used to determine survival from infection., Results: During the study period of 8 years, a total number of 1356 HCTs and 7337 children newly diagnosed for malignancy were analyzed. Diagnosis of acute leukemia was a predisposing factor for SM infection. The cumulative incidence of SM infections was comparable in HCT patients in comparison to PHO (0.81% vs. 0.76%). High rate of trimethoprim/sulfamethoxazole susceptibility among SM isolates was observed in both groups of patients (80.8%). Although this was the drug of choice, survival rates from SM infections were significantly lower in HCT than in PHO (45% vs. 85%, P = 0.001, log-rank test). We found the transplant procedure and lack of clinical resolution after 18 days of antibiotic therapy to be independent mortality risk factors., Conclusions: The risk of SM infections and the occurrence of resistant bacterial strains in allo-HCT patients were comparable to PHO patients. Irrespective of target antibiotic therapy, the outcome of SM infections was better in the PHO setting., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Viral infections can be a serious complication of therapy in children with acute lymphoblastic leukemia (ALL). In this study, we focused on the incidence and the profile of viral infection in children with ALL treated in 17 pediatric oncology centers in Poland in the two-year periods of 2018-2019 and 2020-2021. We also compared the frequency of viral infections in 2018-2019 to that in 2020-2021. In 2020-2021, a total of 192 children with ALL had a viral infection during intensive chemotherapy. A total number of 312 episodes of viral infections were diagnosed. The most common infections detected in the samples were: COVID-19 (23%), rhinovirus (18%), and respiratory syncytial virus (14%). COVID-19 and BK virus infections were the reason for the death 1% of all patients. In 2018-2019, a total of 53 ALL patients who had a viral infection were reported and 72 viral events were observed, mainly adenovirus (48.6%), rotavirus (31.9%), and herpes zoster (8.3%). No deaths were reported during this period. The cumulative incidence of viral infections in 2018-2019 was 10.4%, while for 2020-2021, it was 36.7%. In conclusion, a high incidence of COVID-19 infection was observed among pediatric patients with ALL in Poland. The mortality rate in our material was low. The viral profile in ALL children undergoing chemotherapy can be useful for clinicians to improve prophylactic and therapeutic strategies.

Background and Objectives : One of the most debilitating side effects of chemotherapy is oral mucositis (OM). Photobiomodulation (PBM) demonstrates high efficacy in the management of OM. The aim of the study was to investigate the incidence of oral mucositis and evaluation of the effectiveness of PBM therapy. Materials and Methods : A total of 23 children diagnosed with leukaemia or lymphoma affected by chemotherapy-induced OM were enrolled in the study. OM grade was assessed with the World Health Organization (WHO) scale. Patients completed an approved questionnaire, and blood cell counts were read every 2 days. OM lesions were treated with class IV laser therapy with a frequency of every 48 h and density of 2, 4, 8, 16 or 30 J/cm 2 . The level of pain was measured with VAS scale. Results : The 23 patients developed a total of 41 OM episodes with a mean duration of 7.61 days ± 4.70. Laser therapy showed a great reduction regarding pain and a better function of patients even with neutropenia. Conclusions : Oral mucositis represents a significant burden to children. PBM brings positive aspects for patients; however, the optimal treatment parameters require further study.

Introduction: Myeloid sarcoma (MS) is an extramedullary malignant tumor composed of immature myeloid cells. It occurs in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). MS may coincide with disease diagnosis or precede bone marrow involvement by months or even years; it can also represent the extramedullary manifestation of a relapse (1, 2)., Aim: The aim of this study is to describe clinical characteristics of children diagnosed with MS in Poland as well as to analyze diagnostic methods, treatment, and outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS). The study also attempted to identify factors determining treatment outcomes., Patients: The study group comprised 43 patients (F=18, M=25) aged 0-18 years (median age, 10.0 years; mean age, 8.8 years) diagnosed with MS based on tumor biopsy and immunohistochemistry or identification of underlying bone marrow disease and extramedullary tumor according to imaging findings., Methods: The clinical data and diagnostic and therapeutic methods used in the study group were analyzed. A statistical analysis of the treatment outcomes was conducted with STATISTICA v. 13 (StatSoft, Inc., Tulsa, OK, USA) and analysis of survival curves was conducted with MedCalc 11.5.1 (MedCalc Software, Ostend, Belgium). Statistical significance was considered at p<0.05., Results: In the study group, MS was most frequently accompanied by AML. The most common site of involvement was skin, followed by orbital region. Skin manifestation of MS was more common in the age group <10 years. The most frequent genetic abnormality was the t(8;21)(q22;q22) translocation. The 5-year OS probability (pOS), 5-year RFS probability (pRFS), and 5-year EFS probability (pEFS) were 0.67 ± 0.08, 0.79 ± 0.07, and 0.65 ± 0.08, respectively. In patients with isolated MS and those with concurrent bone marrow involvement by AML/MDS, pOS values were 0.56 ± 0.12 and 0.84 ± 0.09 (p=0.0251), respectively, and pEFS values were 0.56 ± 0.12 and 0.82 ± 0.08 (p=0.0247), respectively. In patients with and without the t(8;21)(q22;q22) translocation, pEFS values were 0.90 ± 0.09 and 0.51 ± 0.14 (p=0.0490), respectively., Conclusions: MS is a disease with a highly variable clinical course. Worse treatment outcomes were observed in patients with isolated MS compared to those with concurrent bone marrow involvement by AML/MDS. Patients with the t(8;21)(q22;q22) translocation were found to have significantly higher pEFS. MS location, age group, chemotherapy regimen, surgery, and/or radiotherapy did not have a significant influence on treatment outcomes. Further exploration of prognostic factors in children with MS is indicated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Samborska, Barańska, Wachowiak, Skalska-Sadowska, Thambyrajah, Czogała, Balwierz, Kołtan, Peszyńska-Żelazny, Wysocki, Ociepa, Urasiński, Wróbel, Węcławek-Tompol, Ukielska, Chybicka, Kitszel, Krawczuk-Rybak, Szmydki-Baran, Malinowska, Matysiak, Mizia-Malarz, Tomaszewska, Szczepański, Chodała-Grzywacz, Karolczyk, Maciejka-Kembłowska, Irga-Jaworska, Badowska, Dopierała, Kurzawa and Derwich.)

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, affecting mainly patients of Slavic origin. It is caused by a defect in the NBN gene, resulting in defective nibrin protein formation. This leads to chromosomal instability, which predisposes to cancer, with lymphoid malignancies predominating. Nibrin is also involved in gonadal development and its disfunction in females with NBS frequently results in a pure gonadal dysgenesis (PGD) causing hypergonadotropic hypogonadism. However, only a few ovarian tumors in NBS patients have been reported to date. We describe the first case of a girl with NBS with PGD, who developed metachronous bilateral ovarian germ cell tumors (dysgerminoma and gonadoblastoma). Pathogenesis of PGD, neoplastic transformation and therapeutic approach in females with NBS are discussed.