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Background: Histologically nephroblastomatosis consists of ≥2 microscopic foci of nephrogenic rests. In contrast, clinically apparent nephroblastomatosis consists of single, multiple or diffuse hyperplastic nephrogenic rests (HNR) that can be mistaken for nephroblastoma on imaging. Their treatment and outcome are as variable as published results.Methods: Analysis of 78 patients having clinically apparent uni- or bilateral nephroblastomatosis out of 2347 patients registered for a renal tumor in the consecutive International Society of Pediatric Oncology (SIOP)93-01/GPOH and SIOP2001/GPOH studies between 1993 and 2014. Results: Median age at diagnosis and follow-up was 13 months (0–12.7 years) and 9.2 years, respectively. 59% of patients were female, 57% had bilateral and 53% multifocal or diffuse nephroblastomatosis. Radiologic diagnosis was conclusive in 67% when reviewed centrally versus 30% without review (p=0.015). 27% of patients developed nephroblastoma(s). On histology 45% were high-risk, 30% intermediate-risk and 25% upfront-surgery-blastemal subtype. 5-year-event-free (EFS), nephroblastoma-free-(NFS) and overall-survival (OS) were 60.7%, 79.8% and 95.5%, respectively. Univariate risk factors for EFS/NFS were female gender (p), bilateral (p=0.002/p=0.03) and diffuse HNR at diagnosis (p), and non-complete remission (non-CR) at the end of first-line-treatment (both p). Gender and non-CR remained significant in multivariate COX regression analysis for EFS (p=0.005 and ), non-CR also for NFS (p=0.002). 34 of 74 evaluable patients achieved CR within 12 weeks after diagnosis, 25 of them had no further treatment and were followed, 9 received chemotherapy. Their EFS was 78% and 100%, respectively.Conclusion: Nephroblastomatosis confronts clinicians with a variety of pitfalls, but overall survival is excellent. However, patients need an extended follow-up for more than a decade. In patients who have achieved CR within 12 weeks, a relatively short treatment is sufficient. Contrary, the risk of progression for patients having bilateral and diffuse HNR is significantly increased, despite prolonged treatment. A clear common terminology is needed for future trials to facilitate true comparability of results.

Acute appendicitis is a rare gastrointestinal complication of anti-cancer chemotherapy and hematopoietic stem cell transplantation. Among a cohort of 2341 hemato-oncologic patients at a pediatric tertiary care cancer center, we identified 21 patients (0.9%) with 23 episodes of acute appendicitis, based on pathological imaging of the appendix and clinical findings. Median age at diagnosis was 10.21 years. Types of underlying disease included acute leukemias (n = 15), solid tumors (n = 4), and aplastic anemia (n = 2). Clinical symptoms seen in > 1 case were recorded for all 23 episodes as follows: abdominal pain, n = 22; abdominal tenderness, n = 4; fever, n = 7; nausea, n = 2; emesis; n = 2; diarrhea, n = 5; and constipation, n = 2. Median leukocyte count at diagnosis was 0.5 × 109/L, with a median of 0.1 × 109/L for the absolute neutrophil count (ANC). All patients received broad-spectrum antibiotics and 18/23 (78%) patients underwent uneventful appendectomy after a median of 5 days and with a median ANC of 0.7 × 109/L. Median duration until continuation of chemotherapy was 17 days for the 20 cases of appendicitis occurring during the patients’ disease course. Overall, 5/21 (19%) patients died including one related to the appendicitis itself which progressed to a typhlitis and was due to a fungal infection. The other fatalities were transplant- (n = 2) and leukemia-related (n = 2). Acute appendicitis is a rare and usually not life-threatening event in pediatric hemato-oncologic patients, which, if managed by prompt administration of broad-spectrum antibiotics (and antimycotics), can be safely followed by an elective (delayed) appendectomy, even before complete recovery of the neutrophils is achieved.

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.

While survival rates in paediatric acute lymphoblastic leukaemia (ALL) nowadays exceed 90%, systemic ALL relapse, especially after haemopoietic stem cell transplantation (HSCT), is associated with a poor outcome. As there is currently no standardized treatment for this situation, individualized treatment is often pursued. Exemplified by two clinical scenarios, the aim of this article is to highlight the challenge for treating physicians to find a customized treatment strategy integrating the role of conventional chemotherapy, immunotherapeutic approaches and second allogeneic HSCT. Case 1 describes a 2-year-old girl with an early isolated bone marrow relapse of an infant KMT2A-rearranged B-cell precursor ALL after allogeneic HSCT. After bridging chemotherapy and lymphodepleting chemotherapy, chimeric antigen receptor (CAR) T-cells (tisagenlecleucel) were administered for remission induction, followed by a second HSCT from the 9/10 human leukocyte antigen (HLA)-matched mother. Case 2 describes a 16-year-old girl with a late, isolated bone marrow relapse of B-cell precursor ALL after allogeneic HSCT who experienced severe treatment toxicities including stage IV renal insufficiency. After dose-reduced bridging chemotherapy, CAR T-cells (tisagenlecleucel) were administered for remission induction despite a CD19- clone without prior lymphodepletion due to enhanced persisting toxicity. This was followed by a second allogeneic HSCT from the haploidentical mother. While patient 2 relapsed around Day + 180 after the second HSCT, patient 1 is still in complete remission >360 days after the second HSCT. Both cases demonstrate the challenges associated with systemic ALL relapse after first allogeneic HSCT, including chemotherapy-resistant disease and persisting organ damage inflicted by previous therapy. Immunotherapeutic approaches, such as CAR T-cells, can induce remission and enable a second allogeneic HSCT. However, optimal therapy for systemic ALL relapse after first HSCT remains to be defined.

Although the fate of nephrogenic rests varies, they are known to be precursors of Wilms tumour. Thus, nephrogenic rests require adequate treatment to prevent malignant transformation. We added 13-cis retinoic acid to the standard chemotherapy with vincristine and actinomycin-D in two patients with bilateral nephrogenic rests/nephroblastomatosis. Patient 1 also had a history of Wilms tumour. 46 (patient 1) and 81 (patient 2) months after end of treatment, both patients show stable conditions with no signs of relapse or progressive disease. Our observation supports further investigation of retinoic acid in patients with nephrogenic rests and nephroblastomatosis.

Myelofibrosis is associated with a wide variety of neoplastic and non-neoplastic bone marrow diseases, predominately myeloproliferative neoplasms and acute myeloid leukemia. The following case documents an unusual patient presenting with pancytopenia and acute myelofibrosis accompanied by precursor B-cell acute lymphoblastic leukemia. This very rare clinical presentation raises questions concerning the relationship between concurrent occurrence of acute myelofibrosis and acute lymphoblastic leukemia.

Rothia mucilaginosa is part of the oral and upper respiratory tract flora. Usually, this gram-positive coccus is not pathogenic; however, in the setting of immunosuppressed hosts, it can cause life-threatening infections as an opportunistic pathogen. Among a cohort of 1511 hematologic-oncologic patients at a pediatric tertiary care cancer center, we identified five cancer patients (0.35%) within a period of 10 years having a proven Rothia mucilaginosa bacteremia (1 culture positive: n = 3/5; > 1 culture positive: n = 2/5). With prompt and adequate antibiotic treatment, infection resolved rapidly before recovery of neutrophils and without any sequelae, suggesting that Rothia mucilaginosa bacteremia without organ involvement is not exceptionally problematic in pediatric cancer patients.

The overall outcome for children with nephroblastomas is excellent when treated according to protocols that include surgery, chemotherapy, and, in selected cases, radiotherapy. This study was conducted to provide population-based data on Austrian children who had been treated in neoadjuvant nephroblastoma trials between October 1988 and July 2001. One hundred and forty-eight children with newly diagnosed untreated renal tumors were registered in the Austrian–Hungarian Wilms Tumor Study (AHWTS) 1989 (N = 63) and the SIOP 93-01/GPOH Study (N = 85). After a median follow-up of 11.8 years from diagnosis, 130 patients have been reported to be alive; 18 patients have died. Three patients had carcinoma and three had nephroblastomatosis; the 5-year event-free survival (EFS) and overall survival (OS) rates for the remaining 142 patients were 83 ± 3 % and 91 ± 2 %, respectively (SIOP 93-01/GPOH trial, 5-year EFS 85 ± 4 %, OS 95 ± 2 %; AHWTS 1989 trial, 5-year EFS 79 ± 5 %, OS 86 ± 5 %). Outcome was better for low-risk pathology (N = 14; 5-year EFS 92 ± 8 %, OS 100 %) than for intermediate-risk (N = 106; 5-year EFS 89 ± 3 %, OS 94 ± 2 %) and high-risk pathology (N = 22; 5-year EFS 50 ± 11 %, OS 68 ± 10 %; P

Benigne Neubildungen des Knochens und des Gelenkknorpels, welche in der Regel nicht aggressiv wachsen und nicht metastasieren, sind meist asymptomatisch und werden demnach meistens zufallig entdeckt. Schmerzen konnen auftreten, wenn eine Irritation der anliegenden Strukturen (zum Beispiel Sehnen oder Nerven) vorliegt oder wenn durch die Schwachung der Knochen eine pathologische Fraktur auftritt. Man unterscheidet Tumoren, die von Knochen- oder Knorpelgewebe ausgehen, sowie fibrose und zystische Lasionen und die Langerhanszell-Histiozytose. Von den nicht neoplastischen Erkrankungen ist vor allem die Osteomyelitis in differentialdiagnostische Uberlegungen einzubeziehen.

The aim of this study was to investigate repeatability of cysteinyl-leukotrienes (cys-LT) measurements in nasal lavage fluid (NLF) and to determine if cys-LT levels in NLF are related to asthma severity in children. As a second outcome, we investigated if cys-LT in NLF reflect lower airway inflammation as assessed by exhaled NO measurement. To assess the repeatability of cys-LT measurements, two NLF samples were obtained from eight healthy controls 24 h apart. Sixty-nine asthmatic children (mean age; range: 12.8; 7.3-17.7 yr), which were grouped according to asthma severity were studied cross-sectionally on one occasion. Cys-LT in NLF were analyzed using a specific enzyme immunoassay, exhaled NO, and pulmonary function parameters were measured. The coefficient of repeatability for the repeated cys-LT measurements was 1.45 pg/ml. Cys-LT levels in NLF differed significantly between asthma severity groups (p < 0.001): mild intermittent: [median (IQR)] 6.88 pg/ml (2.00-27.87); mild persistent: 21.09 pg/ml (4.50-84.67); and moderate persistent asthmatics: 36.41 pg/ml (11.03-118.40). Concentration of cys-LT in NLF and exhaled NO was positively correlated (r = 0.85; p < 0.001). In conclusion, concentration of cys-LT in NLF correlates with asthma severity in children and is related to lower airway inflammation.