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Abstract Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a rare overgrowth condition caused by a pathogenic variant in the phosphatase and tensin homolog (PTEN) gene and belongs to a group of disorders called PTEN hamartoma tumor syndrome (PHTS). The diagnosis is often complicated by great phenotypic diversity. Furthermore, to this date treatment options are limited. Here we performed a systematic review using PubMed, Cochrane, and Scopus databases to identify cases of pediatric patients diagnosed with BRRS and summarized information about the clinical presentation, treatment, and long-term patient care. A total of 83 pediatric patients with BRRS were identified. The most common clinical findings were macrocephaly (77%) and developmental disorders (63%). Surgical interventions were the treatment of choice, described in 19 articles. Patient surveillance was proposed in 15 case reports and mostly aimed at periodic cancer screening. Recognition of BRRS clinical symptoms and early referral to a geneticist is important for better disease control and overall prognosis. As targeted treatment is still lacking, symptom relief and long-term surveillance remain the main management strategies.

Inequalities in research and innovations affect childhood cancer survival across Europe. Vilnius University Hospital Santaros Klinikos (VULSK, the coordinator) and eight research-intensive institutions from seven European countries implemented the TREL project (Twinning in Research and Education to improve survival in childhood solid tumours in Lithuania) supported by the Horizon 2020 Widening programme. TREL aimed to enhance translational, clinical, and survivorship research in paediatric CNS, neuroblastoma, and renal tumours to improve future treatment outcomes in Lithuania. From January 2021 to December 2023, 49 VULSK professionals and 55 peers from partner institutions collaborated in this twinning program. Achievements after three years were: nine educational events, the initiation of basic and clinical research on fertility preservation, ten VULSK researchers joining international research groups, six signed agreements to participate in international academic clinical trials and the implementation of the European Survivorship Passport. Thirty patients received individual treatment recommendations following multidisciplinary discussions with experts from partner institutions. Twenty-five rare genetic variants were classified by the twinning bioinformatician teams with direct consequences on patient management. In conclusion, coordination of the Horizon 2020 project enhanced VULKS’s research capacities, networking channels and attractiveness for industry and academia-initiated innovative actions that will improve survival rates in the long run.

BackgroundTo overcome knowledge gaps and optimize long-term follow-up (LTFU) care for childhood cancer survivors, the concept of the Survivorship Passport (SurPass) has been invented. Within the European PanCareSurPass project, the semiautomated and interoperable SurPass (version 2.0) will be optimized, implemented, and evaluated at 6 LTFU care centers representing 6 European countries and 3 distinct health system scenarios: (1) national electronic health information systems (EHISs) in Austria and Lithuania, (2) regional or local EHISs in Italy and Spain, and (3) cancer registries or hospital-based EHISs in Belgium and Germany. ObjectiveWe aimed to identify and describe barriers and facilitators for SurPass (version 2.0) implementation concerning semiautomation of data input, interoperability, data protection, privacy, and cybersecurity. MethodsIT specialists from the 6 LTFU care centers participated in a semistructured digital survey focusing on IT-related barriers and facilitators to SurPass (version 2.0) implementation. We used the fit-viability model to assess the compatibility and feasibility of integrating SurPass into existing EHISs. ResultsIn total, 13/20 (65%) invited IT specialists participated. The main barriers and facilitators in all 3 health system scenarios related to semiautomated data input and interoperability included unaligned EHIS infrastructure and the use of interoperability frameworks and international coding systems. The main barriers and facilitators related to data protection or privacy and cybersecurity included pseudonymization of personal health data and data retention. According to the fit-viability model, the first health system scenario provides the best fit for SurPass implementation, followed by the second and third scenarios. ConclusionsThis study provides essential insights into the information and IT-related influencing factors that need to be considered when implementing the SurPass (version 2.0) in clinical practice. We recommend the adoption of Health Level Seven Fast Healthcare Interoperability Resources and data security measures such as encryption, pseudonymization, and multifactor authentication to protect personal health data where applicable. In sum, this study offers practical insights into integrating digital health solutions into existing EHISs.

Background. Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods. We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan–Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results. The presence of metastases (3y-EFS: 0.33 vs. 0.68; P

BackgroundThe 5-year survival rate of childhood cancer exceeds 80%, however, many survivors develop late effects including infertility. The aim of this study was to evaluate the current status of oncofertility care at Vilnius University Hospital Santaros Klinikos (VULSK) within the framework of the EU-Horizon 2020 TREL project.MethodsAll parents or patients aged 12–17.9 years treated from July 1, 2021 until July 1, 2022 were invited to complete an oncofertility-care-evaluation questionnaire. After completing the questionnaire, patients were triaged to low-risk (LR) or high-risk (HR) of gonadal damage using a risk stratification tool (triage). Data was assessed using descriptive statistics.ResultsQuestionnaires were completed by 48 parents and 13 children triaged as 36 (59%) LR and 25 (41%) HR patients. Most HR respondents (21/25, 84%) were not counseled by a fertility specialist. Six boys (4 HR, 2 LR) were counseled, none of the girls was counseled. Three HR boys underwent sperm cryopreservation. Only 17 (27.9%, 9 HR, 8 LR) respondents correctly estimated their risk. All counseled boys (n = 6) agreed the risk for fertility impairment had been mentioned as compared to 49.1% (n = 27) of uncounseled. All counseled respondents agreed they knew enough about fertility (vs. 42%).ConclusionsRespondents counseled by a fertility specialist were provided more information on fertility than uncounseled. HR patients were not sufficiently counseled by a fertility specialist. Based on the current experience oncofertility care at VULSK will be improved.

Purpose: Radiation therapy (RT) is an integral part of Ewing sarcoma (EwS) therapy. The Ewing 2008 protocol recommended RT doses ranging from 45 to 54 Gy. However, some patients received other doses of RT. We analyzed the effect of different RT doses on event-free survival (EFS) and overall survival (OS) in patients with EwS. Methods and Materials: The Ewing 2008 database included 528 RT-admitted patients with nonmetastatic EwS. Recommended multimodal therapy consisted of multiagent chemotherapy and local treatment consisting of surgery (S&RT group) and/or RT (RT group). EFS and OS were analyzed with uni- and multivariable Cox regression models including known prognostic factors such as age, sex, tumor volume, surgical margins, and histologic response. Results: S&RT was performed in 332 patients (62.9%), and 145 patients (27.5%) received definitive RT. Standard dose ≤ 53 Gy (d1) was admitted in 57.8%, high dose of 54 to 58 Gy (d2) in 35.5%, and very high dose ≥ 59 Gy (d3) in 6.6% of patients. In the RT group, RT dose was d1 in 11.7%, d2 in 44.1%, and d3 in 44.1% of patients. Three-year EFS in the S&RT group was 76.6% for d1, 73.7% for d2, and 68.2% for d3 (P = .42) and in the RT group 52.9%, 62.5%, and 70.3% (P = .63), respectively. Multivariable Cox regression revealed age ≥ 15 years (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.63-4.38) and nonradical margins (HR, 1.76; 95% CI, 1.05-2.93) for the S&RT group (sex, P = .96; histologic response, P = .07; tumor volume, P = .50; dose, P = .10) and large tumor volume (HR, 2.20; 95% CI, 1.21-4.0) for the RT group as independent factors (dose, P = .15; age, P = .08; sex, P = .40). Conclusions: In the combined local therapy modality group, treatment with higher RT dose had an effect on EFS, whereas higher dose of radiation when treated with definitive RT was associated with an increased OS. Indications for selection biases for dosage were found. Upcoming trials will assess the value of different RT doses in a randomized manner to control for potential selection bias.

Abstract Background Currently the five-year survival of childhood cancer is up to 80% due to improved treatment modalities. However, the majority of childhood cancer survivors develop late effects including infertility. Survivors describe infertility as an important and life-altering late effect. Fertility preservation options are becoming available to pre- and postpubertal patients diagnosed with childhood cancer and fertility care is now an important aspect in cancer treatment. The use of fertility preservation options depends on the quality of counseling on this important and delicate issue. The aim of this manuscript is to present a questionnaire to determine the impact of fertility counseling in patients suffering from childhood cancer, to improve fertility care and evaluate what patients and their parents or guardians consider good fertility care. Methods Within the framework of the EU-Horizon 2020 TREL project, a fertility care evaluation questionnaire used in the Netherlands was made applicable for international multi-center use. The questionnaire to be used at least also in Lithuania, incorporates patients’ views on fertility care to further improve the quality of fertility care and counseling. Results evaluate fertility care and will be used to improve current fertility care in a national specialized pediatric oncology center in the Netherlands and a pediatric oncology center in Lithuania. Conclusion An oncofertility-care-evaluation questionnaire has been developed for pediatric oncology patients and their families specifically. Results of this questionnaire may contribute to enhancement of fertility care in pediatric oncology in wider settings and thus improve quality of life of childhood cancer patients and survivors.

Hematopoietic stem cell transplantation (HSCT) is a complex procedure that is curative for several fatal pediatric malignancies and non-malignant diseases. Despite its complexity, potential toxicity, and high costs HSCT has become a standard procedure worldwide for several decades. Pediatric HSCT programs encounter several specific challenges. The rarity and heterogeneity of primary diseases, result in an almost 10-fold inferior number of pediatric HSCT as compared to adults. In contrast to the adult programs, where autologous HSCT is more common, allogeneic HSCT (that is more complex) prevails in pediatric setting which is underpinned by a higher number of inborn disorders transplanted in early childhood. In Lithuania, the pediatric HSCT program (EBMT CIC* 508) was launched at Vilnius University Hospital Santaros Klinikos in February 2002. Currently, this is the only specialized pediatric HSCT center in Lithuania and in the Baltic countries. Since 2011 it is a reference center for Latvian children who need autologous or allogeneic transplantation. Here we summarize conference proceedings presented at the scientific event “Pediatric hematopoietic stem cell transplantation in Lithuania – 20 years of progress through collaboration”. The meeting held on September 22-23, 2022, in Vilnius and aimed at commemorating 20 years of the launch of the pediatric transplant program in Lithuania. The event pursued sharing the experience in the field of pediatric HSCT in the Baltic countries. Given a very small population in all three Baltic countries, Lithuania, Latvia, and Estonia face an additional challenge in maintaining sufficient transplant volume and gaining experience. Several distinguished speakers from USA, Denmark, Italy, Germany, Spain, UK and Ukraine shared their expertise in the field and emphasized the crucial role of national and international collaboration to achieve progress in the management of this very rare and complex procedure that offers cure for otherwise fatal pediatric conditions.

Abstract Pediatric very rare tumors (VRTs) represent a heterogeneous subset of childhood cancers, with reliable survival estimates depending dramatically on each (un)registered case. The current study aimed to evaluate the number of VRTs among Lithuanian children, to assess the impact of the registration status on survival rates and to track changes in treatment outcomes over the 16-year study period. We performed a population-based retrospective study across children below 18 years old diagnosed with VRTs in Lithuania between the years 2000 and 2015. The identified cases were cross-checked with the Lithuanian Cancer Registry—a population-based epidemiology cancer registry—for the fact of registration and survival status. The overall survival was calculated in relation to the registration status and treatment period. Thirty-seven children with VRTs were identified within the defined time frame. Six of them (16.2%) were not reported to the Lithuanian Cancer Registry at diagnosis. The probability of overall survival at 5 years (OS5y) differed significantly between the registered (n = 31) and unregistered (n = 6) cohorts: 51.6% versus 100%, respectively (p = 0.049). A 5-year survival estimate for children diagnosed with a VRT at the age of 0–14 years differed by 10 percentage points according to the registration completeness: 52.1% calculated for the entire cohort versus 42.1% for registered patients only. The OS5y has not improved over the analyzed period: 61.1% in 2000–2007 versus 57.9% in 2008–2015 (p = 0.805). The survival continued to decline beyond 5 years post-diagnosis due to late cancer-related adverse events: 59.5% of patients were alive at 5 years as compared to 44.3% at 10 years. The OS5y of children affected by VRT was lower than in more common childhood cancers. The survival rate of the unregistered patients may lead to misinterpretation of treatment outcomes. Meticulous registration of VRTs is crucial for correct evaluation of treatment outcomes, especially across small countries with few cases.

Abstract Background ABL-class and JAK-STAT signaling pathway activating alterations have been associated with both a poor post-induction minimal residual disease (MRD) response and an inferior outcome in B-cell acute lymphoblastic leukemia (B-ALL). However, in most of the studies patients received non-uniform treatment. Methods We performed a population-based analysis of 160 (122 pediatric and 38 adult) Lithuanian BCR-ABL1-negative B-ALL patients who had been uniformly treated according to MRD-directed NOPHO ALL-2008 protocol. Targeted RNA sequencing and FISH analysis were performed in cases without canonical B-ALL genomic alterations (high hyperdiploids and low hypodiploids included). Results We identified ABL-class fusions in 3/160 (1.9%) B-ALL patients, and exclusively in adults (p = 0.003). JAK-STAT pathway fusions were present in 4/160 (2.5%) cases. Of note, P2RY8-CRLF2 fusion was absent in both pediatric and adult B-ALL cases. Patients with ABL-class or JAK-STAT pathway fusions had a poor MRD response and were assigned to the higher risk groups, and had an inferior event-free survival (EFS) / overall survival (OS) compared to patients without these fusions. In a multivariate analysis, positivity for ABL-class and JAK-STAT fusions was a risk factor for worse EFS (p = 0.046) but not for OS (p = 0.278) in adults. Conclusions We report a low overall frequency of ABL-class and JAK-STAT fusions and the absence of P2RY8-CRLF2 gene fusion in the Lithuanian BCR-ABL1 negative B-ALL cohort. Future (larger) studies are warranted to confirm an inferior event-free survival of ABL-class/JAK-STAT fusion-positive adult patients in MRD-directed protocols.

Background and objectives: Acute lymphoblastic leukaemia (ALL) is associated with a cytokine imbalance and oxidative stress, which can be aggravated by malnutrition. Malnutrition, defined by the World Health Organisation (WHO) as obesity or undernutrition, can affect treatment complications and outcomes. Therefore, we aimed to analyse the change in the body mass index (BMI) z-score during induction, as well as evaluate the impact of childhood malnutrition on fevers at an ALL presentation and early response to therapy. Methods: An observational cohort study of 50 consecutive children with ALL, diagnosed in 2019–2022, was performed. Patients were divided into age groups of 0–5, 6–11, and 12–17 years. BMI-for-age z-scores were used to define undernutrition and overnutrition according to WHO growth standards. Results: The number of patients with an abnormal BMI increased from 3 (6%) at diagnosis to 10 (20%) at the end of induction (from 2 (4%) to 6 (12%) in overweight/obese, and from 1 (2%) to 4 (8%) in underweight patients). At the end of induction, all overweight/obese patients were 0–5 years old. On the other hand, a statistically significant decrease in the mean BMI z-score among patients aged 12–17 was observed (p = 0.005). The mean BMI z-score differed statistically significantly among children aged 0–5 presenting with and without fever (p = 0.001). The minimal residual disease (MRD) level at the end of induction was not related to BMI at diagnosis. Conclusions: Despite the use of steroids, adolescents are prone to losing weight during an ALL induction, in contrast to preschool children, who tend to gain weight under the same treatment. BMI at diagnosis was related to a fever of ≥38 °C (at ALL presentation) in the 0–5 age group. The results emphasise the importance of careful nutritional status monitoring, with younger and older children as important target groups for weight gain and weight loss interventions, respectively.

BackgroundHalf the children with high-risk neuroblastoma die with widespread metastases. Molecular radiotherapy is an attractive systemic treatment for this relatively radiosensitive tumor. 131I-mIBG is the most widely used form in current use, but is not universally effective. Clinical trials of 177Lutetium DOTATATE have so far had disappointing results, possibly because the administered activity was too low, and the courses were spread over too long a period of time, for a rapidly proliferating tumor. We have devised an alternative administration schedule to overcome these limitations. This involves two high-activity administrations of single agent 177Lu-DOTATATE given 2 weeks apart, prescribed as a personalized whole body radiation absorbed dose, rather than a fixed administered activity. “A phase II trial of 177Lutetium-DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma - LuDO-N” (EudraCT No: 2020-004445-36, ClinicalTrials.gov Identifier: NCT04903899) evaluates this new dosing schedule.MethodsThe LuDO-N trial is a phase II, open label, multi-center, single arm, two stage design clinical trial. Children aged 18 months to 18 years are eligible. The trial is conducted by the Nordic Society for Pediatric Hematology and Oncology (NOPHO) and it has been endorsed by SIOPEN (https://www.siopen.net). The Karolinska University Hospital, is the sponsor of the LuDO-N trial, which is conducted in collaboration with Advanced Accelerator Applications, a Novartis company. All Scandinavian countries, Lithuania and the Netherlands participate in the trial and the UK has voiced an interest in joining in 2022.ResultsThe pediatric use of the Investigational Medicinal Product (IMP) 177Lu-DOTATATE, as well as non-IMPs SomaKit TOC® (68Ga-DOTATOC) and LysaKare® amino acid solution for renal protection, have been approved for pediatric use, within the LuDO-N Trial by the European Medicines Agency (EMA). The trial is currently recruiting. Recruitment is estimated to be finalized within 3–5 years.DiscussionIn this paper we present the protocol of the LuDO-N Trial. The rationale and design of the trial are discussed in relation to other ongoing, or planned trials with similar objectives. Further, we discuss the rapid development of targeted radiopharmaceutical therapy and the future perspectives for developing novel therapies for high-risk neuroblastoma and other pediatric solid tumors.

Background: Acute kidney injury (AKI) is a frequent and widely recognized complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite relatively high prevalence, AKI after allo-HSCT and its risk factors in children remain obscure. The aim of this study was to describe the prevalence and course of AKI during the first 100 days after allo-HSCT in children and to investigate its associations with baseline characteristics.Methods: Retrospective single-center chart review of all patients under 18 who underwent allo-HSCT during 2011–2017 was performed. AKI was defined using the pediatric RIFLE criteria and only the patients with pRIFLE stage I (eGFR decrease by 50% or more) or higher were considered for the analysis. Recurrent AKI and acute kidney disease (AKD) were defined according to the Acute Disease Quality Initiative consensus. Demographic, clinical, and procedure-related characteristics were recorded at the day of HSCT.Results: Fifty-one patients (68.6% boys) with a median age of 9 years (range: 0.25–17) were included. During a median follow-up of 82 (IQR, 60–98) days, 27 (52.9%) patients experienced a total of 39 AKI episodes, translating into one AKI episode per 100 patient days. Multiple AKIs occurred in 11 (21.6%) patients and 18 (35.3%) progressed to AKD. Four patients died, all with ongoing or previous AKI. Patients with AKD were, on average, older (10 vs. 6 years; p = 0.03) and had higher baseline body mass index (BMI) [standard deviation score (SDS) 0.83 vs. 0.04, p = 0.05], whereas patients with recurrent AKI had higher baseline estimated glomerular filtration rate (eGFR) (244.1 vs. 193.9 ml/min/1.73 m2, p = 0.02). In the adjusted Cox models (HR; 95% CI), older age (1.10; 1.01–1.20) was associated with higher risk of overall AKI and higher eGFR (1.02; 1.01–1.04) was associated with higher risk of recurrent AKI, while older age (1.17; 1.04–1.31), higher eGFR (HR 1.01; 1.0–1.02), and higher BMI SDS (1.66; 1.01–2.72) were associated with higher risk of AKD.Conclusions: AKI is a frequent early complication of allo-HSCT in children, and approximately one fifth experience AKI recurrence and one third develop AKD. Older age, higher BMI, and higher eGFR at the day of transplant may have an effect on the risk of AKI development and its course.

Background. Population-based EUROCARE-5 studies demonstrated that childhood cancer survival rates in Lithuania were 10–20% lower than the European mean. We aimed to analyse the change in the outcome of treatment of paediatric malignancies in Lithuania over 30 years. Methods. A single-centre retrospective analysis of children below 18 years of age treated for cancer at Vilnius University Hospital Santaros Klinikos between 1982 and 2011 was carried out. The minimal requirement of 5-year follow-up after diagnosis was specified for survival estimation. The vital status was assessed using data from the population-based Lithuanian Cancer Registry. To evaluate changes over time, the entire cohort was split into three groups according to the time of diagnosis: 1982–1991, 1992–2001, and 2002–2011. Results. A total of 1268 children met the inclusion criteria. The shortest median follow-up was 8.9 (IQR 6.4–11.5) years for patients treated in the third decade. The 5-year overall survival of the entire cohort increased from 37.3% (95% CI 30.2–44.3) in 1982–1991 to 70.7% (95% CI 66.4–74.1) in 2002–2011 (p < 0.0001). The same trend was evident when calculated separately for leukaemia (p < 0.0001), lymphoma (p < 0.0005), and solid tumours (p < 0.004). The percentage of cure rose from zero in the early years of the period analysed to 80% in 2010 and 2011. The improvement in the treatment outcome was attributable to the reduction of treatment-related mortality from 45.8% in 1982–1991 to 12.4% in 2002–2011 and disease recurrence from 30.4% to 19.6% for the same periods, respectively. Conclusions. Significant progress in the cure rate of children treated for cancer at our institution was observed over 30 years. Collaborative national and international clinical and research efforts are crucial to ensure further advances in care and cure.

Background: Variants in recombination-activating genes (RAG) are common genetic causes of autosomal recessive forms of combined immunodeficiencies (CID) ranging from severe combined immunodeficiency (SCID), Omenn syndrome (OS), leaky SCID, and CID with granulomas and/or autoimmunity (CID-G/AI), and even milder presentation with antibody deficiency.Objective: We aim to estimate the incidence, clinical presentation, genetic variability, and treatment outcome with geographic distribution of patients with the RAG defects in populations inhabiting South, West, and East Slavic countries.Methods: Demographic, clinical, and laboratory data were collected from RAG-deficient patients of Slavic origin via chart review, retrospectively. Recombinase activity was determined in vitro by flow cytometry-based assay.Results: Based on the clinical and immunologic phenotype, our cohort of 82 patients from 68 families represented a wide spectrum of RAG deficiencies, including SCID (n = 20), OS (n = 37), and LS/CID (n = 25) phenotypes. Sixty-seven (81.7%) patients carried RAG1 and 15 patients (18.3%) carried RAG2 biallelic variants. We estimate that the minimal annual incidence of RAG deficiency in Slavic countries varies between 1 in 180,000 and 1 in 300,000 live births, and it may vary secondary to health care disparities in these regions. In our cohort, 70% (n = 47) of patients with RAG1 variants carried p.K86Vfs*33 (c.256_257delAA) allele, either in homozygous (n = 18, 27%) or in compound heterozygous (n = 29, 43%) form. The majority (77%) of patients with homozygous RAG1 p.K86Vfs*33 variant originated from Vistula watershed area in Central and Eastern Poland, and compound heterozygote cases were distributed among all Slavic countries except Bulgaria. Clinical and immunological presentation of homozygous RAG1 p.K86Vfs*33 cases was highly diverse (SCID, OS, and AS/CID) suggestive of strong influence of additional genetic and/or epigenetic factors in shaping the final phenotype.Conclusion: We propose that RAG1 p.K86Vfs*33 is a founder variant originating from the Vistula watershed region in Poland, which may explain a high proportion of homozygous cases from Central and Eastern Poland and the presence of the variant in all Slavs. Our studies in this cohort of RAG1 founder variants confirm that clinical and immunological phenotypes only partially depend on the underlying genetic defect. As access to HSCT is improving among RAG-deficient patients in Eastern Europe, we anticipate improvements in survival.

Transient abnormal myelopoiesis (TAM) is a unique entity that usually occurs in children with Down syndrome (DS) or with trisomy 21 mosaicism. The somatic GATA1 mutation is a distinct feature of TAM. At presentation, TAM can resemble congenital leukemia (CL), which unlike TAM has an extremely poor prognosis and requires prompt therapeutic interventions. Therefore, correct and timely distinction between the two entities is crucial. We report a case of a phenotypically normal infant diagnosed with CL during the first weeks of life that retrospectively was reassessed as TAM. No acute myeloid leukemia (AML) specific mutations were found except for trisomy 21 confined exclusively to leukemic blasts. Retrospectively GATA1 mutation was also detected in malignant cells, but somatic genome appeared to be intact.

(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems and modalities; (2) Methods: A cross-sectional questionnaire of relevant PTLD practices in pediatric transplantation was sent to multidisciplinary teams from 17 European center members of ERN TransplantChild to evaluate the centers’ approach strategies for diagnosis and treatment and how current practices impact a cross-sectional series of PTLD cases; (3) Results: A total of 34 SOT programs from 13 European centers participated. The decision to start preemptive treatment and its guidance was based on both EBV viremia monitoring plus additional laboratory methods and clinical assessment (61%). Among treatment modalities the most common initial practice at diagnosis was to reduce the immunosuppression (61%). A total of 126 PTLD cases were reported during the period 2012–2016. According to their histopathological classification, monomorphic lesions were the most frequent (46%). Graft rejection after PTLD remission was 33%. Of the total cases diagnosed with PTLD, 88% survived; (4) Conclusions: There is still no consensus on prevention and treatment of PTLD, which implies the need to generate evidence. This might successively allow the development of clinical guidelines.

Introduction. Wilms tumour (WT) is the most common childhood abdominal malignancy, with an average annual incidence of 1 in 10,000 children. The study published in 2002 reported lower survival rates of WT in Lithuania in comparison to the data of SIOP-9 study and the European Organization for Research and Treatment of Cancer (EORTC). We aimed to assess current diagnostic approach and treatment results of patients with WT treated at our institution and to compare the results with the previously published study. Materials and methods. A retrospective single-centre study was performed. 48 patients with WT registered at the institutional database from 2000 to 2018 were enrolled. An estimated 5-year overall survival (OS5y) and 2-year event-free survival (EFS2y) by stage and risk groups was calculated using IBM SPSS. A comparative analysis of two time periods – 2000–2008 and 2009–2018 – was carried out. Results. Forty-two (87.5%) patients presented with localised disease and 6 (12.5%) with primary metastatic disease. The majority of cases were of the intermediate-risk group (77%). The OS5yof all analysed children was 86.4%. The EFS2y was 88.9% in stage I, 91.7% in stage II, 83.3% in stage III, and 50% in stage IV. The EFS2y was 100% in the low-risk group, 86.5% in the intermediate-risk group, and 25% in the high-risk group. Improvement of outcomes was observed over the analysed period: OS5y changed from 81.0% in 2000– 2008 to 92.6% in 2009–2018. Among 48 cases, ten patients showed recurrence: eight – early relapse and two – late relapse. Six patients died. Conclusions. WT was diagnosed at early stages in most cases. The survival was better among the patients diagnosed in earlier stages and with favourable risk group. Better survival rates were observed in patients treated in 2009–2018 compared to the 2000–2008 period.

Radiation-induced sarcoma (RIS) has been reported as a late secondary malignancy following radiotherapy for various types of cancer with a median latency of 10 years. We describe an early RIS that developed in an adolescent within three years of treatment (including PD-L1 check-point inhibitor Nivolumab) of a relapsed classic Hodgkin lymphoma (HL) and was diagnosed post-mortem. The patient died of the progressive RIS that was misleadingly assumed to be a resistant HL based on the positive PET/CT scan. Repetitive tumor biopsies are warranted in cases of aggressive and multi-drug resistant HL to validate imaging findings, ensure correct diagnosis and avoid overtreatment.

Introduction. Ewing sarcoma (ES) is a rare and aggressive malignant neoplasm that mostly affects children and adolescents. Recent studies reported a gap of 20% in childhood cancer survival rates between the Northern/ Western and the Eastern European countries. We aimed to analyse the survival of patients treated for ES at our institution, to evaluate its correspondence to current survival rates in the expert centres, and to assess changes in treatment outcomes over time. Materials and methods. A retrospective single-centre study was performed. Children under 18 years of age, diagnosed and treated for Ewing sarcoma/PNET at our institution from 2000 to 2014 were included. To assess the hypothesized improvement of treatment outcomes over time, a comparative analysis of two time periods – 2000–2007 and 2008–2014 – was carried out. Five-year overall survival (OS5y) and disease-free survival (DFS5y) were chosen as primary study end-points. Clinical and laboratory data were retrieved from patient records. Results. In total, 40 patients were included in the study: 24 (60%) males and 16 (40%) females. Twenty-eight children (70%) presented with local and 12 (30%) with primary metastatic disease. Over the analysed time frame, improvement in treatment outcomes was observed: DFS5y improved from 46% in 2000–2007 to 61% in 2008–2014 (p = 0.27), whereas OS5y changed minimally from 62% in 2000–2007 to 65% in 2008–2014. Increase in DFS5y was more prominent for localized disease –from 50% in 2000–2007 to 74% in 2008–2014 (p = 0.14). Prognosis of initial metastatic disease remained poor with DFS5y: 25% in 2000–2007 and 38% in 2008–2014. Patients’ median follow-up was 12.3 years (the range from 8.1 to 15.6) and 3.9 years (the range from 1.1 to 8.0) in the first and second study groups, respectively. Conclusions. OS5y of the entire patient cohort did not change considerably over time and remained slightly inferior compared to the best reported survival rates. There was an evident trend for improvement of DFS5y in localized disease. Survival of children with primary metastases remained poor despite slight increase in DFS5y. Implementation of international clinical trials, consolidation of multidisciplinary approach, patients’ concentration and widening of research activities could be beneficial for the treatment of children in the future.

Background. Neuroblastoma (NB) is the most common extracranial solid tumour in children. This is a very rare disease with heterogeneous biology varying from complete spontaneous regression to a highly aggressive tumour responsible for 15% of malignancy-related death in early childhood. Analyses of survival rates in Europe have shown a considerable difference between Northern/Western and Eastern European countries. Treatment results of NB in Lithuania have never been analyzed. Aim. To assess the survival rate of children with NB according to initial spread of the disease, age at diagnosis, the MYCN amplification, risk group, and treatment period. Patients and methods. A retrospective single-centre analysis of patients’ records was performed. Children diagnosed and treated for NB between 2000 and 2015 at the Centre of Paediatric Oncology and Haematology of the Children’s Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos were included. The patients were divided into three groups according to the spread of the disease: group 1 – patients with local NB older than 12 years of age; group 2 – stage IV patients, also called the M stage; group 3 – infants with stages 4S and MS. The patients were stratified into three risk groups – low, intermediate and high risk. Estimates of five-year overall survival (OS5y) were calculated using the Kaplan-Meier method comparing survival probability according to spread of the disease, age at diagnosis, the MYCN amplification, risk group and treatment period (2000–2007 vs 2008–2015). Results. Overall 60 children (31 girls and 29 boys) with NB were included. The median age at diagnosis was 1.87 years (ranged from 4 days to 15 years). Seventy-eight percent of cases were found to be differentiated or undifferentiated NB, 22% – ganglioneuroblastoma. The local form of the disease was predominant: 57% (34/60) of patients were allocated to the group 1, 37% (22/60) with initial metastatic disease were assigned to group 2, and infants with 4S or MS stage comprising 7% (4/60) allocated to group 3, respectively. The probability of OS5y for the entire cohort was 71% with the median follow-up of 8.8 ± 4.8 years. The probability of OS5y for local disease (group 1) was significantly higher compared to metastatic disease (group 2) (94% vs. 34%, p = 0.001, respectively) as well as for infants compared to children older than 12 months at the time of diagnosis (90% vs 60%, p = 0.009, respectively). The MYCN gene amplification had a negative influence on OS5y, with 78% of MYCN-negative patients surviving in comparison to 40% of MYCN-positive patients who did not survive (p = 0.153). The high-risk patients had significantly worse OS5y than children with intermediated or low risk (35% vs. 82% vs. 100%, respectively, p = 0.001). Comparison of OS5y between two treatment periods in the entire patient population revealed a non-significant increase in survival from 66% in the 2000–2007 period to 82% in the 2008–2015 period (p = 0.291), mostly due to a dramatic improvement achieved for high-risk patients whose survival rate increased from 9% in the 2000–2007 period to 70% in the 2008–2015 period (p = 0.009). Conclusions. There was a slight predominance of low-risk patients, probably due to a higher number of infants. A better probability of OS5y was confirmed in infants with local disease and in MYCN-negative patients. The OS5y for children treated for NB at our institution over 16 years increased from 66% in the 2000–2007 period to 82% in the 2008–2015 period with the most significant improvement achieved for high risk patients. The current survival rate of children treated for NB at our institution is in line with the reported numbers in Northern and Western European countries.

Hemofagocitinė limfohistiocitozė – tai sindromas, besivystantis dėl sutrikusios imuninio atsako aktyvacijos ir slopinimo pusiausvyros. Išskiriama pirminė (genetinė arba šeiminė) sindromo forma, nulemta genų, dalyvaujančių imuninių ląstelių sąveikoje, mutacijų; ir antrinė (sporadinė) forma, besivystanti dėl infekcijos, navikinio, autoimuninio proceso ar metabolinių sutrikimų. Antrinės hemofagocitinės limfohistiocitozės genetinis pagrindas kol kas nežinomas. Pirminei ir antrinei formoms būdingas toks pats specifinis hiperuždegiminių reakcijų bei klinikinių simptomų kompleksas, kuriuo grindžiama patologijos diagnostika. Tačiau pirminės ir antrinės formų atskyrimas dažnai tampa iššūkiu dėl patologijos retumo, plataus klinikinių požymių spektro, dėl riboto specifinių testų prieinamumo ir, svarbiausia, gydymo taktikos ypatumų. Etiopatogenetinis pirminės formos gydymas yra skubi alogeninė kraujodaros kamieninių ląstelių transplantacija, be kurios išeitis neišvengiamai fatali. Antrinės formos gydymas priklauso nuo klinikinės išraiškos ir ją sukėlusios infekcijos pobūdžio. Labai svarbi laiku atlikta diagnostika norint kuo skubiau pradėti tinkamą gydymą bei pagerinti išgyvenamumą. Hemofagocitinės limfohistiocitozės gydymą komplikuoja didelis su gydymu susijęs mirtingumo dažnis bei ligos polinkis recidyvuoti.