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Therapy results in pediatric Hodgkin lymphoma reflect remarkable progress in pediatric oncology. In the last decade, relevant development of new therapeutic options for children with refractory or relapsed disease has been made. In this study, we retrospectively analyzed therapy results and risk factors in children treated in a single oncology center according to five therapeutic protocols. Data from 114 children treated by a single institution between 1997 and 2022 were analyzed. Classic Hodgkin lymphoma therapy results were divided into four therapeutic periods: 1997–2009, 2009–2014, 2014–2019, and 2019–2022. For nodular lymphocyte-predominant Hodgkin lymphoma, data from one therapeutic protocol was analyzed. For the entire group, the 5-year probability of overall survival was 93.5%. There were no statistically significant differences between therapeutic periods. The occurrence of B symptoms at diagnosis and incidence of relapse were risk factors for death (p = 0.018 and p p = 0.086). The 5-year probability of event-free survival for all patients was 91.3%. Five patients died, and the most common cause of death was relapse. Modern therapeutic protocols in pediatric Hodgkin lymphoma are marked by excellent outcomes. Patients with disease relapses have a notably high risk of death, and the development of new therapeutic options for this group remains one of the main goals of current trials.

Introduction: We analyzed the epidemiology and outcomes of treatment of invasive fungal disease (IFD) in children during anticancer therapy (PHO, pediatric hematology and oncology) or after hematopoietic cell transplantation (HCT) over a period of eight consecutive years in a single-center study. Material and methods: Overall, a total of 254 HCTs were performed, and 415 children were newly diagnosed for malignancy. Incidence, epidemiology and outcome of IFD were analyzed. Results: The cumulative incidence of any IFD was 32.6% in allo-HCT, 22.2% in PHO, and 6.0% in auto-HCT patients. The incidence of proven +probable IFD was 12.6%, 10.4%, and 6.0%, respectively. As many as 77.0% HCT and 67.4% PHO of fungal episodes occurred in acute leukemia patients: the highest incidence of any IFD was observed for acute lymphoblastic leukemia (29.3% in HCT; 40.5% in PHO) and for acute myeloblastic leukemia (51.1% in HCT; 65.0% in PHO) patients. There were no significant differences in the incidence of fungal infections in both allo-HCT and PHO patients between the 2-year periods. Factors contributing to an increased risk of IFD in allo-HCT patients were: CMV replication, and acute and chronic graft-versus-host disease (GvHD). Survival from IFD was 91.9% in PHO, and 78.1% in HCT patients. Fungal pneumonia in HCT patients resolved in 62.9%, while in PHO patients it resolved in 93.5%. Conclusions: The risk of IFD in allo-HCT patients is much higher than in auto-HSCT and PHO patients. The outcome of IFD is better in PHO and auto-HCT than in allo-HCT settings.

The concept of ambulatory/outpatient transplantations is based on variable distribution and location of performing basic stages of hematopoietic cell transplantation (HCT): central venous catheter insertion, high-dose chemotherapy administration, hematopoietic stem cells infusion, and supportive care during aplastic phase. Our objective was to present the concept of outpatient transplantation and to review the available data on prophylaxis of infectious complications early after outpatient transplantation. In our general recommendations, patients, family members and caregivers should be trained before discharge on the careful monitoring of fever and other signs and symptoms of infections. The clinical evaluation of patients should be performed twice weekly until clinical recovery. Standard transplant approach should be applied for dose of CD34 + cells, use of granulocyte colony-stimulating factor after HSC infusion, use of primary antimicrobial prophylaxis, and supportive care. Antimicrobial prophylaxis for ambulatory auto-HCT patients should be the same as for a conventional inpatient setting, including antibacterial, antiviral and anti- Pneumocystis jiroveci pneumonia (PjP) prophylaxis. For patients undergoing allo-HCT in an outpatient setting, the general recommendations are the same as for auto-HCT patients. Frequent monitoring of immunosuppressive treatment is recommended. Monitoring for cytomegalovirus infection and Aspergillus galactomannan should be the same as for conventional allo-HCT. Primary anti-mold prophylaxis is strongly suggested. Ambulatory auto-HCT is feasible and safe, making this an important alternative option. This is an especially attractive option for multiple myeloma patients, as it has a very low transplant-related mortality risk. Obviously, ambulatory auto-HCT cannot be regarded as a routine procedure.

IntroductionLeukemia belong to 31% of all childhood malignancies. Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric leukemia accounting for 80–85% of all cases. Progress in diagnostics and therapy of leukemia is dependent on international cooperation. The objective of the study was the analysis of non-hematological toxicity during intensive chemotherapy according to two consecutive intercontinental protocols.Patients and methodsA total number of 210 children diagnosed for ALL who were treated in single center between 2002 and 2018 were divided in two groups defined by therapeutic protocol: ALL IC-BFM 2002 (group 1) and ALL IC-BFM 2009 (group 2). Data were entered prospectively from 2002 into international ALL IC-BFM 2002 and ALL IC-BFM 2009 registry. Non-hematological toxicity was analyzed according to the criteria followed in protocols, compatible with CTCAE criteria.ResultsThe most frequent toxicities included hepatic toxicity with transaminitis and hyperbilirubinemia, infections, oral mucositis and gut toxicity with vomiting, and/or diarrhea. Non-hematological toxicity episodes calculated as a ratio per patient were comparably often observed in both the groups; however, the distribution was different. There were more grade III and less grade II toxicities. This was mainly related to significant increase in the rates of infections and transaminitis. However, there was a significant decrease in vomiting and central and peripheral neurotoxicity.ConclusionsIntensive treatment of ALL is burdened with frequent severe toxic and infectious complications. Further progress in therapy of pediatric ALL is dependent on sophisticated supportive therapy and very well experienced and knowledgeable therapeutic team.

Background/AimNeurofibromatosis type 1 (NF1) is characterized by the occurrence of multisystem tumors. The objective of this study was to analyze the demographic and oncological profile of 830 NF1-individuals regarding prevalence, type, and spectrum of malignancy.Patients and methodsThe medical records of patients diagnosed with NF1 with a median age of 22.1 years (range: 0.8–81.6 years) who were followed up for malignancies from 1999 to 2018 were retrospectively reviewed.ResultsThe prevalence of malignancy occurring in patients diagnosed with NF1 was 34.8% (289/830). The most common types of neoplasia encompassed tumors strictly associated with NF1, including plexiform neurofibromas (PNF; 200/830; 24.1%) and optic pathway gliomas (91/830; 11%). The prevalence of PNFs-transforming to malignant peripheral nerve sheath tumors (MPNST) was 3.5% (7/200). The prevalence of other tumors was 4.8% (40/830). One patient was diagnosed with acute myeloid leukemia (AML), thus the risk of hematological malignancies among all patients with NF1 was 0.1% (1/830). In the population of patients with malignancies, 43/289 (14.9%) individuals were diagnosed with more than one malignancy.ConclusionsThe odds ratio (OR) of malignancy in a studied cohort of patients with NF1 was 23 (p < 0.001), while the OR of hematological malignancy was 5.1 (p = 0.1) in comparison with the general population.

Background/aim The objective of the study was to propose clinical guidelines for the use of minimally invasive surgery (MIS) in pediatric oncology. Patients and methods Two groups of experts, including pediatric surgeons and pediatric oncologists were created in order to establish strategies of diagnostic and therapeutic surgical management in pediatric oncology. Results On the basis of the analysis of the existing literature, we elaborated guidelines that were graded according to the simple practical clinical system: yes/no. This project was dedicated to the following topics: adrenal tumors including neuroblastoma, renal tumors including Wilms tumor (nephroblastoma), ovarian tumors and pulmonary nodules and metastases (osteosarcoma). Conclusion Although existing data do not allow the recommendation of the use of MIS for all indications, this technique should currently be regarded as a standard of care in several areas of pediatric oncology.

Background A retrospective analysis was performed to investigate the survival outcomes in pediatric acute lymphoblastic leukemia (ALL) based on time period. We hypothesized that improvement has been obtained with the time-dependent therapeutic era and rise in the gross domestic product (GDP) and Human Development Index (HDI). Materials and methods Data from 710 children who were treated for ALL between 1958 and 2018 at a single pediatric center were analyzed for probability of 5-year overall survival (pOS), event-free survival (pEFS) and relapse risk (pRR). Time periods were defined by the treatment protocols used in seven consecutive therapeutic eras. Results Over the 60-year period analyzed, pOS increased from 1.2% to 90.7%, pEFS from 1.2% to 86.6%, and pRR decreased from 98.8% to 9.9% for patients treated in the past decade. Risk of mortality for patients who received chemotherapy and hematopoietic cell transplant was reduced to 9.9% in the recent era, however, no statistically significant survival difference was found between patients treated with stem cell transplant and those not. Conclusion The therapeutic era, related to improved GDP and HDI, was a statistically significant predictor of increased OS from ALL.

Background/aim Nivolumab is an immune checkpoint inhibitor with high antitumor activity in selected neoplasms. The aim of the study was to evaluate the efficacy and safety of nivolumab in pediatric patients with various types of highly malignant advanced tumors. Patients and methods Ten patients with a median age of 15.1 years were included in the study. The indications for treatment were: malignant skin melanoma (n=5), brain tumor (n=2), malignant melanoma of the brain (n=1), Hodgkin lymphoma (n=1) and soft tissue sarcoma (n=1). Results Complete disease remission was observed in 4 patients. Overall survival at 24 months from diagnosis for the entire group was 0.36. Two patients receiving combination therapy of nivolumab and ipilimumab did not achieve a remission. Adverse events of immunotherapy were observed in 4/10 patients. Conclusion Nivolumab is a promising option in pediatric advanced malignancies. Treatment with immunotherapy was relatively well tolerated, and emerging side-effects were manageable.

Resveratrol, polyphenol naturally occurring in grapes or nuts, has anti-cancer properties in the treatment of neuroblastoma – the most common childhood solid tumor. It affects cancer cells by increasing apoptosis, inducing cell necrosis and reducing tumor mass. Mechanism of action – (1) converting procaspases, mainly procaspases three and nine into active forms – caspases, (2) blocking kinases, and also (3) leading the cell to the S-cell cycle, where it is most effective while increasing the concentration of cyclin E and lowering the concentration of p21 protein. In vitro, as well as, rodent animal models studies are available and show promising results. Therapeutic doses, currently within 10–100 μmol/L, are also being tested, as well as other forms of resveratrol, such as its trans-4,4′-dihydroxystilbene analog and polyphenol lipoconjugates. In our review, we presented the known molecular mechanisms of polyphenol anti-tumor activity against neuroblastoma and discussed the studies confirming its effectiveness.

Background/aim Immune recovery is a key factor in the management of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study analyzed the factors contributing to immune reconstitution after allo-HSCT. Patients and methods Overall, 65 children with malignant or non-malignant diseases were included in multivariate analyses. Results The following factors contributed to a faster immune recovery: peripheral blood as a stem cell source and reactivation of CMV infection for CD3+ and CD4+ lymphocyte subpopulations; reactivation of CMV infection for CD8+ subset; donor EBV-IgG+ and no EBV reactivation for CD19 lymphocytes; recipient age below 10 years and peripheral blood as a stem cell source for NK cells. For CD2 and CD4/CD8 ratio no factor was significant in multivariate analysis. Conclusion Patients receiving a graft from an EBV-IgG-positive donor and not having early EBV post-transplant viremia show faster recovery of the B-cells, while patients with early CMV-DNA-emia have a better re-establishment of T-cell subsets.

Introduction Bone abnormalities occur often in patients with neurofibromatosis type 1 (NF1). This suggests that the metabolism of bone tissue may be affected in these patients. Objective Evaluation of markers of bone mineral density and bone metabolism with respect to bone abnormalities in patients with NF1. Methods A total number of 57 NF1 patients and 145 controls were studied. Activity or concentrations of following markers of bone mineralization and bone metabolism were performed on all patients: bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG) and collagen type I crosslinked C-telopeptide (CTX). Results Bone abnormalities were observed in 75.44% NF1 patients. NF1 patients had a significant decrease in BMD z-score compared with controls (–0.679 ± 1.157 vs 0.000 ± 1.000 g/cm2, p Conclusions Sceletal defects often occurs in NF1 patients, with scoliosis being the most common pathology. NF1 can predispose to premature loss of bone mass. Analyzed markers indicate that bone resorption predominates over ossification in NF1 patients.

Introduction Nonneoplasmatic pineal cyst changes are quite often found during brain MRI of pediatric patients. Usually, they are asymptomatic; however, clinical signs such as headache, sight disorders, dizziness or hydrocephalia may occur. Objective Epidemiological and clinical evaluation of the occurrence of pineal cysts in children treated in a single oncological ward over a period of 7 years. Methods Retrospective analysis of the patients hospitalized in the Department of Pediatrics, Hematology and Oncology in Bydgoszcz and diagnosed for pineal cyst by MRI. Results The incidence of pineal cysts in patients who underwent MRI for various reasons was 5.2%. In 52% of the patients, MRI examination was performed to check their reported headache. The size of the cysts in MRI varied from 3 mm to 21 mm. Control MRI was performed in 64% of the children after 1–12 months. In 2 of them, little reduction of the size of the cyst was observed; in one case, slight enlargement was observed, and in the remaining, the size was stable. None of the patients required neurosurgical intervention. Conclusions Pineal cysts were diagnosed in 5.2% of the children with central nervous system disorder symptoms. In half of the cases, headache was the reason for starting the diagnostic procedures. Size of the pineal cysts observed in the population of pediatric patients usually does not exceed 10 mm. Most of the pineal cysts have mild clinical character but always require excluding the presence of malignant process. No clinical progression was observed within 6–12 month observation in any of the patients.

Almost all individuals with neurofibromatosis type 1 (NF1) develop peripheral nerve sheath tumors (PNSTs), mainly benign neurofibromas, however about 10% of PNSTs will undergo transformation to malignant peripheral nerve sheath tumors (MPNSTs). Surgical treatment of PNSTs has traditionally been regarded as a standard approach. The availability of new agents that target specific molecular pathways involved in the pathogenesis of PNST has led to a number of clinical trials, which resulted in increased chances for better survival and quality of life. This review presents the latest evidence and clinical implications for new therapies of PNSTs in patients with NF1 emphasizing the potential benefit from the use of Ras/MAPK pathway inhibitors, immunotherapy, chemotherapy or radiation therapy. We present evaluation of current knowledge on available treatment modalities.

Background/aim Neurofibromatosis type 1 (NF1) is characterized by the occurrence of multisystem tumors, among which the most characteristic are optic pathway gliomas (OPGs) and plexiform neurofibromas (PNFs). With the development of new anticancer drugs targeting the immune system, it is important to examine the immunological status of patients with NF1. Furthermore, the immune system has been suggested as a probable modulator of NF1-associated phenotypes. The objective of this study was the analysis of lymphocyte subset populations with respect to the presence of PNFs and OPGs. Patients and methods Fifty-three patients with NF1 diagnosed with OPG/PNF were analyzed for lymphocyte subpopulations. Results Significantly lower levels of B-cells, T-cells and natural killer (NK) cells were observed in the group of patients with PNFs compared to those with OPG. Conclusion Our observation may indicate a correlation between weakened functioning of the immune system and the formation of PNFs.

High-dose chemotherapy with autologous hematopoietic stem cell transplantation improves event-free survival in patients with high-risk neuroblastoma. However, in heavily pretreated patients, poor marrow function can be an obstacle in the successful proceeding of therapy. Priming with plerixafor plus filgrastim is an option for effective mobilization and collection of stem cells. In addition, thrombopoietin agonist eltrombopag can improve the outcome of posttransplantation thrombocytopenia and poor graft function in the posttransplant setting. We describe a case of a child with high-risk neuroblastoma, for whom plerixafor and eltrombopag were used as an effective and safe supportive therapy.

Background/aim Malignant melanoma is a rare disease in the pediatric population and there are no recommendations regarding its management in children, while the current standard of care in metastatic or unresectable melanoma in adult patients includes immunotherapy (anti-CTLA-4 and anti-PD-1 antibodies). Advances in the management of adults with melanoma offer the prospect of promising therapeutic options for children. Case report We describe a case of a 7-year-old patient with recurrent metastatic melanoma, for whom pembrolizumab was used as an adjuvant therapy on compassionate use basis. Conclusion Due to adverse events, the treatment was discontinued after 5 months of pembrolizumab, but with 12-months of follow-up, patient remains in complete remission.

BACKGROUND/AIM Neurocutaneous disorders, also referred as phacomatoses, are congenital disorders manifesting at different ages with central nervous system and cutaneous abnormalities. Analysis of the demographic and clinical profile of patients with phacomatoses in the context of the incidence and spectrum of malignancy. MATERIALS AND METHODS This is a retrospective analysis of 20 years of data in a single-center study in Poland. RESULTS Phacomatoses were diagnosed in 45.6% (913/2,003) of referred patients, including 61.4% children. The distribution of phacomatoses included: neurofibromatosis type 1 (NF1) in 92.4%, tuberous sclerosis complex (TSC) 3.9%, neurofibromatosis type 2 (NF2) 2.0%, Klippel-Trenaunay syndrome 0.5%, Von Hippel-Lindau syndrome 0.5%, and other sporadic diseases 0.7%. Non-phacomatosis patients were diagnosed mainly for cafe-au-lait-macules (42.8%). The frequency of malignancy was 9.4% (86/913), including 9.1% in patients with NF1; 27.8% in NF2; and 8.3% in TSC. Multiple malignancies were diagnosed in 0.7% and 7% of all phacomatosis and malignancy-diagnosed patients, respectively. CONCLUSION The risk of malignancy in patients with phacomatoses was 21.3-fold higher than in the general population. The risk of secondary malignancy was 7%.