Search

Between July 1994 and December 1996, PBSC were mobilized in 28 patients with poor-risk hematological malignancies and solid tumors. CD34+ cells were positively immunoselected using the Ceprate CS System. By December 1996, 22 patients had been reinfused with a median of 3.325 (0.078–9.5) × 106/kg CD34+ cells. In three patients unselected back-up PBSC had to be transfused along with selected CD34+ cells because of a CD34+ cell number <0.5 × 106/kg. G-CSF (10 μ g/kg) was started on day +1 and all patients engrafted within a median day number of 12 (range, 10–22) until leukocytes >1.0 × 109/l and a median day number of 56 (range, 10–180) until platelets >20.0 × 109/l (ie platelet transfusion independence). Time to leukocyte and platelet recovery was significantly shorter in patients receiving >2.0 × 106/kg purified CD34+ cells as compared to patients reinfused with <2.0 × 106/kg CD34+ cells. The hematopoietic recovery time was similar to that of 18 historical control patients treated with unseparated ABMT ± PBSCT with the exception of a significantly faster leukocyte engraftment in patients receiving >2.0 × 106/kg CD34+ cells and a significantly delayed platelet recovery time in patients receiving <2.0 × 106/kg purified CD34+ cells. There was a trend for a better overall survival and a lower probability of progression/relapse as compared to the historical controls. We observed five episodes of serious opportunistic infections (three pulmonary fungal infections, two cases of cryptosporidiosis) after the take. Four of these patients had been reinfused with <2.0 × 106/kg CD34+ cells probably indicating a delayed immune reconstitution after CD34+-selected PBSCT. [ABSTRACT FROM AUTHOR]

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome whose development can be triggered by environmental, autoimmune, and/or genetic factors. The latter comprises germ line pathogenic variants in genes that bring about habitually predisposing syndromes as well as immune deficiencies that do so only occasionally. One of these disorders is the autosomal dominant form of chronic mucocutaneous candidiasis (CMC), which is defined by germ line STAT1 gain-of-function (GOF) pathogenic variants. The resultant overexpression and constitutive activation of STAT1 dysregulate the Janus kinase/signal transducer and activator of transcription 1 (STAT) signaling pathway, which normally organizes the development and proper interaction of different components of the immunologic and hematopoietic system. Although SAA is an extremely rare complication in this disorder, it gained a more widespread interest when it became clear that the underlying causative pathomechanism may, in a similar fashion, also be instrumental in at least some of the idiopathic SAA cases. Based on these premises, we present herein what is the historically most likely first cord blood-transplanted SAA case in a CMC family with a documented STAT1 GOF pathogenic variant. In addition, we recapitulate the characteristics of the six CMC SAA cases that have been reported so far and discuss the significance of STAT1 GOF pathogenic variants and other STAT1 signaling derangements in the context of these specific types of bone marrow failure syndromes. Because a constitutively activated STAT1 signaling, be it driven by STAT1 GOF germ line pathogenic variants or any other pathogenic variant-independent events, is apparently important for initiating and maintaining the SAA disease process, we propose to acknowledge that SAA is one of the definite disease manifestations in STAT1 -mutated CMC cases. For the same reason, we deem it necessary to also incorporate molecular and functional analyses of STAT1 into the diagnostic work-up of SAA cases., 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 © 2024 Fink, Höpfl, Witsch-Baumgartner, Kropshofer, Martin, Fink, Heeg, Peters, Zschocke and Haas.)

This prospective multicentre trial evaluated the safety and the efficacy of a thiotepa/melphalan-based reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) in children and adolescents with chronic myeloid leukaemia (CML) in chronic phase (CP). Thirty-two patients were transplanted from matched siblings or matched unrelated donors. In 22 patients, HSCT was performed due to insufficient molecular response or loss of response to first- or second-generation tyrosine kinase inhibitor (TKI), with pretransplant BCR::ABL1 transcripts ranging between 0.001% and 33%. The protocol included a BCR::ABL1-guided intervention with TKI retreatment in the first year and donor lymphocyte infusions (DLI) in the second-year post-transplant. All patients engrafted. The 1-year transplant-related mortality was 3% (confidence interval [CI]: 0%-6%). After a median follow-up of 6.3 years, 5-year overall survival and event-free survival are 97% (CI: 93%-100%) and 91% (CI: 79%-100%) respectively. The current 5-year leukaemia-free survival with BCR::ABL1 <0.01% is 97% (CI: 88%-100%) and the current TKI- and DLI-free survival is 95% (CI: 85%-100%). The incidence of chronic graft-versus-host disease (GvHD) was 32%, being severe in four patients (13%). At last follow-up, 31 patients are GvHD-free and have stopped immunosuppression. RIC HSCT following pretreatment with TKI is feasible and effective in children and adolescents with CP-CML with an excellent disease-free and TKI-free survival., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Thromboembolic complications are well known in the treatment of childhood acute lymphoblastic leukemia. Over the years it has not been possible to reach a consensus on a possible prophylaxis of thromboembolic events during intensive therapy. Only the administration of enoxaparin was able to achieve evidence in the literature to date., Methods: In this retrospective study, 173 childhood leukemia patients were treated over 20 years with a thromboembolic prophylaxis including enoxaparin and AT III during induction therapy with L-asparaginase and cortisone., Results: We here report the effectiveness of administration of enoxaparin and AT III in childhood leukemia, showing a strikingly low prevalence of deep vein thrombosis (2.9%). Especially in adolescent patients, a particularly great need for AT III was demonstrated., Conclusions: We recommend thromboembolic prophylaxis with enoxaparin and AT III substitution during induction/reinduction therapy with L-asparaginase and glucocorticosteroids, especially from adolescence onwards., (© 2024. The Author(s).)

Patients' reports of their health status are increasingly used in hematopoietic stem cell transplantation (SCT) to better understand the negative impact on symptom burden and quality of life. Little is known regarding the implementation in routine clinical care, particularly how it can be used to improve supportive care. We sought to the evaluate feasibility of capturing daily patient-reported outcomes (PROs) in the acute phase of SCT to measure physical and psychosocial symptom burden. In this single-center prospective observational study, we assessed daily PRO from conditioning to neutrophil engraftment in children (age 1 to 18 year) who underwent allogeneic or autologous SCT for malignant and nonmalignant disease. The most common acute adverse effects of chemotherapy (pain, nausea, loss of appetite, sleep disturbance, and physical performance impairment) were reported daily via ePROtect, a web-based program designed to integrate health responses. From February 2021 to March 2023, 20 children undergoing allogeneic (allo-) SCT (n = 11) or autologous (auto-) SCT (n = 9) and their proxies consented to participation, all of whom were included in this analysis. A total of 359 PRO questionnaires were completed, corresponding to a median daily completion rate of 72.7% (interquartile range, 60.4% to 83.6%). After conditioning, pain perception anticipated the rise of infectious parameters and the development of mucositis, thus initiating supportive treatment. Patients reported the strongest symptom burden at a median of 8.5 days post-transplantation. At 4 weeks post-transplantation, baseline values were restored for all symptoms. There were no significant differences between auto-SCT and allo-SCT, except for nausea and loss of appetite after administration of antithymocyte globulin in allo-SCT. This study empirically documents the daily health status of children undergoing SCT and proposes an attractive modus operandi on how continuous feedback on health-related symptoms can be integrated into daily clinical practice., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: As one of the few modifiable risk factors, the importance of dietary patterns for both disease prevention and treatment outcome in pediatric oncology has gained increasing popularity. Malnutrition is associated with lower survival rates, tolerance to treatment, and quality of life. Yet, especially in children with malignancies, nutritional deterioration is common, and pediatric cancer patients often present with inadequate intake of micro- and macronutrients alike. Despite the reported widespread use of dietary supplements, few empirical data provide a basis for clinical recommendations, and evidence for their efficacy is inconsistent. Current literature lacks a systematic approach as to how and which supplements should be recommended for specific patients, types of cancer, or during specific treatments. The aim of this review is to highlight the role of the most frequently used nutrients in pediatric malignant diseases and to give a practical guide based on current scientific evidence., Methods: A comprehensive literature search was conducted on PubMed through April 2023 to select meta-analyses, systematic reviews, observational studies, and individual randomized controlled trials (RCTs) of macro- and micronutrient supplementation in pediatric oncology. The search strategy included the following medical subject headings (MeSH) and keywords: "childhood cancer", "pediatric oncology", "nutritional status", "dietary supplements", "vitamins", "micronutrients", "calcium", "magnesium", "vitamin D", "zinc" "glutamine", "selen", and "omega-3 fatty acids". The reference lists of all relevant articles were screened to include potentially pertinent studies., Results: The present review provides a comprehensive and updated overview of the latest evidence about the role of nutrition and diet in pediatric oncology, also focusing on different nutritional interventions available for the management of the disease. We summarize evidence about the importance of adequate nutrition in childhood cancer and the role of several micronutrients and critically interpret the findings. Possible effects and benefits of supplementation during chemotherapy are discussed, as are strategies for primary and secondary prevention., Conclusions: We here describe the obvious benefits of dietary supplementation for childhood cancer. Further large-scale clinical trials are required to verify the impacts of deficiencies and the possible benefits of supplementation and optimal dosages. (337 words).

We conducted a retrospective analysis to determine the potential reduction in treatment burden through the expansion of virtual care among children with leukemia (n = 152). Patients living in urban areas traveled median distances of 1555 km compared with 7536 km for patients living in rural areas (p < .05). For the latter group, a median reduction in travel distance of 3560 km (interquartile range [IQR], 2136-5787 km), travel time of 51 h (IQR, 26-78 h), and CO 2 emissions of 623 kg (IQR, 374-1013 kg) was estimated, if every second visit was replaced by video consultations., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Purpose: Serial assessment of health condition based on self-report made by children and their proxies has consistently shown a lack of congruence. The study explored the discrepancies between mother's, father's, and children's reports on health-related quality of life (HRQOL) during the first two months of pediatric cancer treatment., Methods: In this cohort study, children and parents completed the generic and cancer-specific Pediatric Quality-of-Life Inventory (PedsQL) questionnaires at initial diagnosis and in the subsequent months. Evaluation of discrepancies included intraclass correlations between mother-child and father-child dyads at different domain levels., Results: Thirty-six children with a diagnosis of cancer between May 2020 and November 2021 and their parents were included in this study. At diagnosis, mother-child dyads showed better agreement on more domains of the PedsQL Generic Core Scale than father-child dyads; moderate agreement persisted for both parents at subsequent time points on the physical domain. The disease-specific PedsQL Cancer Module revealed moderate and better agreement for mother-child dyads during active cancer therapy. In particular, agreement of mother-child dyads was pronounced for domains such as worry (0.77 [95% CI 0.52-0.89, P < 0.001]), whereas fathers tended to overestimate the child's symptom burden for most of the remaining domains of the PedsQL Cancer Module., Conclusion: This cohort study shows that both parent proxy reports can provide valid information on child's HRQOL, but that fathers tend to overestimate, particularly for non-observable domains. Proxy reports derived from mothers more closely agreed with children's HRQOL and might be more weighted, if there is uncertainty between parents., (© 2023. The Author(s).)

Venous thromboembolism (VTE) is a well-known complication of the treatment of pediatric acute lymphoblastic leukemia (ALL). We analyzed 1026 ALL patients 1-18-years-old, who were enrolled into the AIEOP-BFM ALL 2000 or 2009 studies in Austria, with regard to the incidence and risk factors of VTE. The 2.5-year cumulative incidence (CI) of VTE ≥ grade 2 was 4%±1% (n = 36/1026). Twenty VTE (56%) were found in the central nervous system (19 cerebral venous sinus and 1 cortical vein thrombosis), and 16 (44%) at other sites (7 deep vein thromboses (DVT) of the lower extremity, 4 DVT of the upper extremity, 4 central venous line-thromboses, 1 pulmonary embolism). Most VTE occurred during induction and early consolidation therapy (81%) and were associated with L-asparaginase within 4 and corticosteroids withing 1 week(s) preceding the event (89 and 86%, respectively). In multivariable analysis, two independent risk factors were found. Patients 10-18-years-old had an increased (hazard-ratio: 2.156, p = 0.0389), whereas treatments in trial AIEOP-BFM ALL 2009 had a lower risk for VTE (hazard-ratio: 0.349, p = 0.0270). In conclusion, the 2.5-year CI of VTE among our pediatric patient cohort was <5% and adolescent age was the main patient-related risk factor. This older age group might benefit from primary prophylactic measures.

Febrile neutropenia secondary to chemotherapy is one of the most critical complications in cancer treatment. The aim of this study was to determine if an increase in the percentage of immature platelet fraction (IPF%) might predict early neutrophil recovery following cytostatic-dependent aplasia. A retrospective cohort study compared serial complete blood counts and the level of C-reactive protein (CRP) following induction chemotherapy for Ewing sarcoma and Non-Ewing sarcoma patients. The measurements were taken on a Sysmex XE-2100 instrument. A total of 287 paired samples from 28 children after the first cycle of chemotherapy were analyzed to test if an increase in the IPF% anticipated the CRP peak and recovery of neutrophil count. The chemotherapy associated nadir of neutrophils, reticulocytes and platelets was reached at 9.7 ± 1.5, 11.0 ± 1.7 and 11.9 ± 0.9 days (mean ± SD) respectively, in Ewing sarcoma patients. Still in severe neutropenia, IPF% was the first parameter that significantly increased and anticipated the CRP peak (11.9 ± 1.6 days, mean ± SD). The IPF% continuously increased (maximum = 6.56% ± 2.8%, mean ± SD) and peaked at 12.2 ± 1.4 days (mean ± SD) after commencement of chemotherapy. Compared to neutrophil recovery (14.6 ± 1.4 days, mean ± SD), the IPF% peak was anticipated by 2.4 days (p = 0.0085). Although variably treated, in non-Ewing sarcoma patients the effect was similar and the IPF% peak anticipated neutrophil recovery by 6.8 ± 4.7 days (p < 0.01). IPF% increased significantly at > 48 h before neutrophil recovery in patients treated with chemotherapy. IPF% is an inexpensive parameter and may be valuable in the management of febrile neutropenia., (© 2023. The Author(s).)

Infections in hematopoietic stem cell transplant (HSCT) remain one of the major causes for morbidity and mortality, and it is still unclear whether knowledge of microbial colonization is important. In this single-center study, we collected weekly surveillance cultures in pediatric recipients of allogenic HSCT from five different body regions and tested for bacteria and fungi. Between January 2010 and December 2021, we collected 1095 swabs from 57 recipients of allogeneic HSCTs (median age: 7.5 years, IQR 1−3: 2.5−11.9). The incidence of positive microbiological cultures (n = 220; 20.1%) differed according to the anatomic localization (p < 0.001) and was most frequent in the anal region (n = 98), followed by the genital, pharyngeal and nasal regions (n = 55, n = 37 and n = 16, respectively). Gram-positive bacteria (70.4%) were the most commonly isolated organisms, followed by fungi (18.6%), Gram-negative (5.5%), non-fermenting bacteria (1.4%), and other flora (4.1%). No association with increased risk of infection (n = 32) or septicemia (n = 7) was noted. Over time, we did not observe any increase in bacterial resistance. We conclude that there is no benefit to surveillance of microbial colonization by culture-based techniques in pediatric HSCT. Sequencing methods might enhance the detection of pathogens, but its role is still to be defined.

Introduction: Mortality in children with hemato-oncologic disease admitted to a pediatric intensive care unit (PICU) is higher compared to the general population. The reasons for this fact remain unexplored. The aim of this study was to assess outcomes and trends in hemato-oncologic patients admitted to a PICU, with analytical emphasis on emergency admissions., Methods: Patients with a hemato-oncologic diagnosis admitted to a tertiary care university hospital PICU between 1 January 2009 and 31 December 2019 were retrospectively analyzed. Additionally, patient mortality 6 months after PICU admission and follow-up mortality until 31 December 2020 were recorded., Measurements and Main Results: We reviewed a total of 701 PICU admissions of 338 children with hemato-oncologic disease, of which 28.5% were emergency admissions with 200 admissions of 122 patients. Of these, 22 patients died, representing a patient mortality of 18.0% and an admission mortality of 11.0% in this group. Follow-up patient mortality was 25.4% in emergency-admitted children. Multivariable analysis revealed severe neutropenia at admission and invasive mechanical ventilation (IMV) as independent risk factors for PICU death ( p = 0.029 and p = 0.002). The total number of PICU admissions of hemato-oncologic patients rose notably over time, from 44 in 2009 to 125 in 2019., Conclusion: Although a high proportion of emergency PICU admissions of hemato-oncologic patients required intensive organ support, mortality seemed to be lower than previously reported. Moreover, in this study, total PICU admissions of the respective children rose notably over time., 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 Pechlaner, Kropshofer, Crazzolara, Hetzer, Pechlaner and Cortina.)

Importance: Patient-reported outcome measurements (PROMs) are emerging as an important component of adult cancer care, but little has been done with regard to PROMs for pediatric cancer care., Objectives: To identify pediatric patients with cancer who are at risk of severe adverse effects of treatment and provide individualized supportive care using PROMs., Design, Setting, and Participants: This single-center cohort study with PROMs implemented in daily clinical routine was conducted from May 1, 2020, to November 15, 2021, among pediatric patients with a cancer diagnosis or their proxies. Inclusion criteria were treatment with chemotherapy and at least 30 days of active participation. Patients were followed up until completion of therapy or through ongoing therapy until November 15, 2021; data were analyzed from November 15, 2021, through January 31, 2022., Exposures: Cancer treatment, including chemotherapy, surgery, and radiotherapy., Main Outcomes and Measures: The primary outcome was occurrence and severity of ubiquitous complications of cancer treatment, such as nausea, appetite loss, pain, sleep disturbance, and deterioration of physical functioning. The secondary outcome was the identification of early and appropriate clinical interventions based on detection of cancer-related symptoms via PROMs., Results: A total of 4410 daily PROMs from 7082 therapy days for 40 children (35 children aged 5-18 years and 5 proxies for children aged 1-4 years) (median age, 9.1 [IQR, 6.3-12.2] years; 26 [65.0%] male) were analyzed during a median follow-up of 145.5 (IQR, 103.8-244.5) days. All participants were White. The overall median completion rate was 60.1% (IQR, 37.9%-81.0%); this rate was slightly lower during home care vs inpatient stay (57.5% [IQR, 30.7%-85.9%] vs 65.0% [IQR, 49.6%-92.5%], respectively; P = .01), with a decreasing trend over time (65.6% [IQR, 51.6%-85.9%] for the first 90 days vs 42.9% [IQR, 29.3%-82.3%] for beyond 90 days; P < .001). Severe symptoms were reported on 657 days (14.9%); most symptoms were associated with physical functioning, followed by pain, sleep disturbance, and nausea and appetite loss. In total, 321 adverse events (AEs) and cases of health deterioration were documented, and PROMs were completed for 251 (78.2%) of these events. Across all AEs, self-reported pain was the most useful marker, particularly when analyzed on the day before onset, and was associated with an odds ratio of 3.65 (95% CI, 1.54-8.62; P = .005) for the presence of mucositis., Conclusions and Relevance: The findings of this cohort study suggest that PROMs reflect daily symptoms in pediatric patients with cancer and assist in clinical management and intervention for AEs.

Second malignant neoplasms (SMN) after primary childhood acute lymphoblastic leukemia (ALL) are rare. Among 1487 ALL patients diagnosed between 1981 and 2010 in Austria, the 10-year cumulative incidence of an SMN was 1.1% ± 0.3%. There was no difference in the 10-year incidence of SMNs with regard to diagnostic-, response- and therapy-related ALL characteristics except for a significantly higher incidence in patients with leukocytes ≥50.0 G/L at ALL diagnosis (2.1% ± 1.0% vs. 0% for 20.0-50.0 G/L, and 1.0% ± 0.3% for < 20.0 G/L; p  = 0.033). Notably, there was no significant difference in the incidence of SMNs between patients with or without cranial radiotherapy (1.2% ± 0.5% vs. 0.8% ± 0.3%; p  = 0.295). Future strategies must decrease the incidence of SMNs, as this event still leads to death in one-third (7/19) of the patients., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations., Methods: We retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0-281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases)., Results: Ten patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5-65). The mean sirolimus level was 8.52 ng/ml (range, 5.38-12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4-6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor-advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course., Conclusion: In the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms., 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 Karastaneva, Gasparella, Tschauner, Crazzolara, Kropshofer, Modl, Pfleger, Burmas, Pocivalnik, Ulreich, Zenz, Schwinger, Beqo, Urban, Haxhija, Lackner and Benesch.)

We report the case of an infant with multicentric myofibromatosis affecting the gastric and intestinal mucosa, leading to continuous intestinal hemorrhage and iron deficiency. Conventional vinblastine and methotrexate combination treatment was administered for 4 months, but persistent intestinal blood loss required repeated blood transfusions. Because of insufficient tumor response to treatment, we opted for the experimental combination of rapamycin and dasatinib. Six weeks after the start of this therapy, hemoglobin levels stabilized without transfusions, and no fecal blood loss was detected. In addition, a follow-up magnetic resonance imaging excluded tumor progression. We here show the effectiveness of an experimental therapy with rapamycin and dasatinib in a child with multicentric myofibromatosis after the failure of conventional therapy with vinblastine and methotrexate., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Nasopharyngeal carcinoma (NPC) in children and young adults has been treated within two consecutive prospective trials in Germany, the NPC-91 and the NPC-2003 study of the German Society of Pediatric Oncology and Hematology (GPOH). In these studies, multimodal treatment with induction chemotherapy, followed by radio (chemo)therapy and interferon-beta maintenance, yielded promising survival rates even after adapting total radiation doses to tumor response. The outcome of 45 patients in the NPC-2003 study was reassessed after a median follow-up of 85 months. In addition, we analyzed 21 further patients after closure of the NPC-2003 study, recruited between 2011 and 2017, and treated as per the NPC-2003 study protocol. The EFS and OS of 66 patients with locoregionally advanced NPC were 93.6% and 96.7%, respectively, after a median follow-up of 73 months. Seven patients with CR after induction therapy received a reduced radiation dose of 54 Gy; none relapsed. In young patients with advanced locoregional NPC, excellent long-term survival rates can be achieved by multimodal treatment, including interferon-beta. Radiation doses may be reduced in patients with complete remission after induction chemotherapy and may limit radiogenic late effects.

Introduction: Gender plays an active role in the incidence and outcome of many infectious and malignant diseases. However, there is still no study examining sex differences for developing bloodstream infections (BSIs) in pediatric patients with cancer. We sought to identify potential gender-specific risk factors for BSIs., Methods: Data were retrospectively analyzed from 621 pediatric patients treated for childhood cancer in a tertiary single center between 1 January 2000 and 31 June 2018. After central venous access device (CVAD) placement, patients were followed up until CVAD was removed or at the most for 1 year. We calculated the gender-specific prevalence for BSIs and compared the causative bacterial strains., Results: Of 621 pediatric patients with cancer (283 girls [45.6%] and 338 boys [54.4%]), 110 patients (41 girls [37.3%] and 69 boys [62.7%]) were identified with a total of 134 BSIs. Girls and boys had a similar incidence for BSI (13%) within the first 3 months of therapy, after which the risk for BSI increased significantly for boys (34% versus 21%, boys versus girls, P = 0.025). Moreover, BSI with gram-positive bacteria affected boys nearly twice as often as girls (29.8% versus 56.5%, girls versus boys)., Conclusions: Future clinical awareness of hygiene-related BSIs in boys could be helpful in identifying areas for improvement., (© 2021. The Author(s).)

Malignant peritoneal mesothelioma (MPM) is an extremely rare entity with a poor prognosis. We report on a 16-year-old boy with ascites and abdominal distension. A computed tomography scan showed peritoneal thickening and a mass adjacent to the transverse colon. Neither repeated cytologic testing of ascitic fluid, nor peritoneal tissue biopsy detected malignant cells. After the patient became progressively comatose, a magnetic resonance imaging scan of the brain showed leptomeningeal enhancement. An autopsy showed MPM infiltrating the pleura and the meninges. This is the first report on meningeal metastasis of MPM in a pediatric patient illustrating the enigmatic behavior of the tumor and highlighting the diagnostic pitfalls., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Childhood patients have high risks for developing debilitating somatic and mental health side-effects as a consequence of the many different approaches employed in treating their cancer. Early recognition and close monitoring of clinical and psychological problems are essential in planning appropriate interventions and preventing further deterioration., Case: ePROtect was established as an easy-to-use application for daily self-reporting of symptoms during cancer therapy. ePROtect includes six to eight questions pertaining to seven common symptoms: appetite loss, fatigue, nausea, pain, physical functioning, cognitive impairments and sleep quality. The case of a child diagnosed with Burkitt leukemia developing chemotherapy-induced oral mucositis in home care is presented to show the therapeutic impact of early symptom detection with a daily web-based tool., Conclusion: This case highlights how electronic patient-reported outcome measures (PROM) can directly facilitate patient care in real time and might be incorporated in future clinical routine., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Several stakeholders, including patients and health care providers, suggest symptom self-reporting measurements for a more patient-directed cancer control approach. However, services tailored to measure daily reporting and implementing it in clinical care are lacking. This study aimed to evaluate the feasibility and value of daily patient-reported outcome measures (PROMs) by children receiving chemotherapy for cancer., Methods: Health status was recorded daily with a web-based child-friendly patient portal (ePROtect). Following aspects of feasibility and usability were assessed: (a) the completion rate and time, (b) user feedback on usability and satisfaction, and (c) the performed interventions if moderate to severe symptom deterioration was noted., Results: Twelve children (median age: 7.2 years) were included. A total number of 891 daily reports were collected during the study period; the median percentage of ePROtect completion days was 85.3% (interquartile range [IQR] 64.2-100.0) and 55.9% (IQR 51.9-76.9) for inpatient and outpatient stay, respectively. Mean time to complete the questionnaire was 47.6 seconds. Severe symptoms were reported in 14.7% of measurement time points, which led to prompt health care interventions in 57 cases, including extension of supportive care (n = 37) and pre-emptive inpatient admissions (n = 5). Over 80% of the patients (10/12) and their proxies (16/18) provided feedback with high rating for satisfaction (>90%) and usefulness (>80%) of ePROtect., Conclusion: Our study shows that daily symptom monitoring is feasible for all children with newly diagnosed cancer aged 5-18 years. Monitoring offers the opportunity to identify symptoms early and trigger appropriate clinical action., (© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Hyponatremia is a well-known adverse event of repeated therapy with vincristine in oncological patients. However, to date, data in pediatric patients with malignant diseases other than acute lymphoblastic leukemia (ALL) are sparse or lacking., Materials and Methods: A retrospective study of 98 pediatric patients was conducted to analyze the incidence of hyponatremia in a Caucasian cohort of newly diagnosed ALL. For comparison, we further examined five other pediatric oncological cohorts (Hodgkin's disease, Ewing sarcoma, Wilms tumor, benign glioma of the CNS, Langerhans cell histiocytosis) that receive alkaloids in their induction regimes., Results: We found a high incidence of hyponatremia (14.7%) in our ALL cohort with a trend toward male patients of elementary school age. None of the affected patients showed neurological symptoms. By comparison, patients from other malignancy groups did not show significant hyponatremia, regardless of their comparable therapy with alkaloids. We here show a noticeable coincidence of hyponatremia and hypertriglyceridemia in ALL patients, indicating a possible role of L-asparaginase-related hypertriglyceridemia in the development of severe hyponatremia in such patients., Conclusion: We report a higher incidence of hyponatremia following vincristine therapy in Caucasian children with ALL than published before. This hyponatremia could not be demonstrated in other oncologic cohorts treated with alkaloids. L-Asparaginase-induced hypertriglyceridemia may play a role in the certainly multifactorial development of hyponatremia in childhood leukemia., 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 © 2021 Salvador, Salvador, Willeit, Kuntner, Haid, Müller, Kropshofer and Crazzolara.)

Background: Management of pediatric post-transplantation lymphoproliferative disorder (PTLD) after hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) is challenging., Aim: This study of 34 PTLD patients up to 19-years old diagnosed in Austria from 2000 to 2018 aimed at assessing initial characteristics, therapy, response, and outcome as well as prognostic markers of this rare pediatric disease., Methods and Results: A retrospective data analysis was performed. Types of allografts were kidney (n = 12), liver (n = 7), heart (n = 5), hematopoietic stem cells (n = 4), lungs (n = 2), multi-visceral (n = 2), small intestine (n = 1), and vessels (n = 1). Eighteen/34 were classified as monomorphic PTLD, with DLBCL accounting for 15 cases. Polymorphic disease occurred in nine, and non-destructive lesions in six cases. One patient had a non-classifiable PTLD. Thirteen/34 patients are surviving event-free in first remission (non-destructive, n = 4/6; polymorphic, n = 4/9; monomorphic, n = 6/18). Fourteen/34 patients lacked complete response to first-line therapy, of whom seven died. Four/34 patients relapsed, of whom two died. In 3/34 patients, death occurred as a first event. The 5-year overall and event-free survival rates were 64% ± 9% and 35% ± 9% for the whole cohort. Among all parameters analyzed, only malignant disease as the indication for transplantation had a significantly poor influence on survival., Conclusions: This study shows PTLD still to be a major cause of mortality following SOT or HSCT in children. A continued understanding of the molecular biology of the disease shall allow to decrease treatment intensity for lower risk patients and to identify patients who may benefit from newer therapy approaches to improve outcome and decrease morbidity., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Introduction: Sufficient empirical antimicrobial therapy in febrile patients with cancer is challenging, owing to the limited arsenal of available antibiotics in an era of growing resistance. Because of the emergence of gram-negative bacteria resistant to ceftazidime and piperacillin, a combination antibiotic therapy was employed that uses meropenem combined with gentamicin and/or vancomycin if the patient further deteriorates., Methods: A retrospective cohort analysis was performed including all patients with catheter-associated bloodstream infections (BSIs) and treated for childhood cancer in a tertiary single centre between 1 January 2000 and 31 June 2018. We calculated the prevalence and the risk for BSIs and compared the in vitro susceptibility to various antimicrobial agents., Results: Of 653 patients with childhood cancer, 113 patients (17.3%) were identified with a total of 139 BSIs, most of them occurring in patients with leukaemia (n = 90, 64.7%) and were associated with gram-positive bacteria (60.5%). In our cohort, all BSIs with gram-negative bacteria exhibited in vitro susceptibility against meropenem alone without any signs of resistance development. The antibiotic coverage of our meropenem-based combination therapy was also highly effective for gram-positive and non-fermenting bacteria. Thus, BSI-related mortality in all 139 BSI episodes was 1.4%. Clostridium difficile infections (CDIs), as main adverse event of carbapenem usage, occurred in only 16 (2.5%) patients., Conclusion: Our meropenem-based combination therapy showed sufficient empirical antibiotic coverage in the majority of BSIs (96.4%) and did not result in an increased rate of unwanted side effects or development of antibiotic resistance.

Background: Malnutrition is common in children with cancer and is associated with adverse clinical outcomes. The need for supportive care is becoming ever more evident and the role of nutrition in oncology is still not sufficiently understood. In particular, the consequences of macro- and micronutrient deficiencies require further research. As epidemiological data suggest anti-tumoral properties of omega-3 (n-3) polyunsaturated fatty acids (PUFAs), we reviewed the role of nutrition and n-3 supplementation in pediatric oncology., Methods: A comprehensive literature search was conducted on PubMed through 5 February 2021 to select meta-analyses, systematic reviews, observational studies, and individual randomized controlled trials (RCTs) on macro- and micronutrient supplementation in pediatric oncology. The search strategy included the following medical subject headings (MeSH) and keywords: "childhood cancer", "pediatric oncology", "nutritional status", "malnutrition", and "omega-3-fatty-acids". The reference lists of all relevant articles were screened to include potentially pertinent studies., Results: We summarize evidence about the importance of adequate nutrition in childhood cancer and the role of n-3 PUFAs and critically interpret findings. Possible effects of supplementation on the nutritional status and benefits during chemotherapy are discussed as well as strategies for primary and secondary prevention., Conclusion: We here describe the obvious benefits of omega-3 supplementation in childhood cancer. Further large scale clinical trials are required to verify potential anti-cancer effects of n-3 fatty acids.

Introduction: Clear cell sarcoma of the kidney (CCSK) is a rare malignant childhood renal tumour. Recently, the central nervous system (CNS) was found to be the most frequent site of relapse associated with a poor outcome. Optimal treatment strategies are scarce., Patients and Methods: Retrospective data analysis of all Austrian children with CCSK. They were enrolled in the Austrian-Hungarian Wilms Tumour Study (AHWTS) 1989, the SIOP93-01 or the SIOP2001 study between 1990 and 2019. Demographic, diagnostic, treatment-related variables and survival data were analysed., Results: We identified 12 children with CCSK (M = 7, F = 5; median age 1.6 years). All had localised disease (stage I: 2; stage II: 2; stage III: 8) at diagnosis, and a first complete remission (CR1) was achieved in 12/12. Six patients are in an ongoing CR1 (median follow-up 10 years). Six other patients had a relapse (local 1; brain 5) a median time of 2.4 years from diagnosis. Two patients died of the disease 4 months and 2.8 years after first relapse. Four of five patients with CNS relapse are in CR2 with a median follow-up time of 9.3 years after relapse diagnosis. Relapse treatment included a combination of chemotherapy, radiation and surgery. Two children received high-dose chemotherapy followed by autologous stem cell rescue, and one child received intrathecal mafosphamide. Long-term side effects after treatment were impaired tubular renal function (n = 4), cardiomyopathy (n = 1) and growth disorders (n = 1)., Conclusions: In this series, the brain was the most common site of relapse. Long-term survival after recurrence was achievable with intensive multimodal therapy., (© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Fluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single-centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin-B (L-AMB) and restricted to high-risk patients only. Vincristine-induced neurotoxicity was significantly reduced under L-AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene-treated patients (P = 0·005). Before 2011, 10 patients developed confirmed IFIs, most of them were infected with Aspergillus species. After risk adaption in 2011, IFIs were completely prevented (P = 0·007). L-AMB prophylaxis is beneficial in childhood leukaemia patients, as it offers effective antifungal activity with improved tolerability as compared to fluconazole. The potential impact of our risk-adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background and Aims: Surgical resection is currently the cornerstone of liver tumor treatment in children. In adults radiofrequency ablation (RFA) is an established minimally invasive treatment option for small focal liver tumors. Multiprobe stereotactic RFA (SRFA) with intraoperative image fusion to confirm ablation margins allows treatment for large lesions. We describe our experience with SRFA in children with liver masses., Methods: SRFA was performed in 10 patients with a median age of 14 years (range 0.5-17.0 years) suffering from liver adenoma ( n  = 3), hepatocellular carcinoma ( n  = 1), hepatoblastoma ( n  = 2), myofibroblastic tumor ( n  = 1), hepatic metastases of extrahepatic tumors ( n  = 2) and infiltrative hepatic cysts associated with alveolar echinococcosis ( n  = 1). Overall, 15 lesions with a mean lesion size of 2.6 cm (range 0.7-9.5 cm) were treated in 11 sessions., Results: The technical success rate was 100%, as was the survival rate. No transient adverse effects higher than grade II (Clavien and Dindo) were encountered after interventions. The median hospital stay was 5 d (range 2-33 d). In two patients who subsequently underwent transplant hepatectomy complete ablation was histologically confirmed. Follow-up imaging studies (median 55 months, range 18-129 months) revealed no local or distant recurrence of disease in any patient., Conclusions: SRFA is an effective minimal-invasive treatment option in pediatric patients with liver tumors of different etiologies.