The CATERPILLAR-study: An assessor blinded randomized controlled trial comparing a taurolidine-citrate-heparin lock solution to a heparin-only lock solution for the prevention of central-line associated bloodstream infections in paediatric oncology patients.

BACKGROUND: Taurolidine-citrate(-heparin) lock solutions (TCHL) are suggested as a promising and safe method for the prevention of central line-associated bloodstream infections (CLABSI). AIM: To investigate the efficacy TCHL for the prevention of CrLABSI in paediatric oncology patients. METHODS: An assessor blinded randomized controlled trial at the Princess Máxima Centre for paediatric oncology, the Netherlands, was performed from 2020-2023. Paediatric oncology patients receiving a tunnelled central venous access device (CVAD) were eligible. A total of 462 patients was required to compare the TCHL to the heparin-only lock (HL). Patients were followed-up for the first 90 days after CVAD insertion. The primary outcome was the incidence of the first CLABSI from CVAD insertion until the end of follow-up. Intention-to-treat and per-protocol analyses were performed. FINDINGS: In total, 232 were randomized in the HL and 231 in the TCHL-group. A total of 47 CLABSIs were observed. The intention-to-treat analysis showed that a CLABSI was observed in 26 (11.2%) of the HL-group patients versus 21 (9.1%) of the TCHL-group patients; incidence rate ratio (IRR) of 0.81 (CI95%0.46-1.45), in favour of the TCHL-group. The per-protocol analysis showed that a CLABSI was observed in 10 (7.9%) of the HL-group patients versus 6 (4.8%) of the TCHL-group patients; IRR of 0.59 (CI95%0.21-1.62) in favour of the TCHL-group. Adverse events were more common in the TCHL-group but rarely reported. CONCLUSION: No difference was detected between the TCHL and HL in the incidence of CLABSI in paediatric oncology patients. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05740150.

Satisfaction of Paediatric Oncology Patients, Survivors, and Nurses with the Position of Their Totally Implantable Venous Access Port (SPACE-Study).

BACKGROUND: To compare paediatric oncologic vascular access ports located on the anterior thoracic wall to ports on the lower lateral thoracic wall, in terms of perceived port-related hindrance and scar-quality. METHODS: A cross-sectional survey study including paediatric oncology patients (≥8-<19 yrs), caregivers (in patients <8 yrs), survivors (>22 yrs with only anterior ports) and nurses of the Princess Máxima Center, the Netherlands, was performed. The survey consisted of questions regarding satisfaction, hindrance during daily life, and port position preference. For survivors, scar-quality was assessed using the validated Patient and Observer Scar Assessment Scale (POSAS 2.0); a high score (i.e., a displeasing scar) was defined as a score higher than the third quartile of the median for that question. RESULTS: In total, 147 participants were included; 83 patients/caregivers, 31 survivors, and 33 nurses. Overall, 81 % was satisfied with the position of their port. Satisfaction, hindrance and complications did not differ between anterior and lower lateral ports. For the anterior position, minimal pressure on the port during daily life was a mentioned reason to prefer this position. For the lower lateral position, less visibility of the scar and easiest access were mentioned. Of all survivors with an anterior port scar, one in five had a displeasing scar and all scars observed were widened. Female patients preferred a lower lateral port, and scar-quality was better for left-sided port scars. CONCLUSION: The port position should be chosen together with patients/caregivers based on the (dis-)advantages of each position, as identified by this study. LEVEL OF EVIDENCE: II.

Tracked ultrasound registration for intraoperative navigation during pediatric bone tumor resections with soft tissue components: a porcine cadaver study.

PURPOSE: Resection of pediatric osteosarcoma in the extremities with soft tissue involvement presents surgical challenges due to difficult visualization and palpation of the tumor. Therefore, an adequate image-guided surgery (IGS) system is required for more accurate tumor resection. The use of a 3D model in combination with intraoperative tracked ultrasound (iUS) may enhance surgical decision making. This study evaluates the clinical feasibility of iUS as a surgical tool using a porcine cadaver model. METHODS: First, a 3D model of the porcine lower limb was created based on preoperative scans. Second, the bone surface of the tibia was automatically detected with an iUS by a sweep on the skin. The bone surface of the preoperative 3D model was then matched with the bone surface detected by the iUS. Ten artificial targets were used to calculate the target registration error (TRE). Intraoperative performance of iUS IGS was evaluated by six pediatric surgeons and two pediatric oncologic orthopedists. Finally, user experience was assessed with a post-procedural questionnaire. RESULTS: Eight registration procedures were performed with a mean TRE of 6.78 ± 1.33 mm. The surgeons agreed about the willingness for clinical implementation in their current clinical practice. They mentioned the additional clinical value of iUS in combination with the 3D model for the localization of the soft tissue components of the tumor. The concept of the proposed IGS system is considered feasible by the clinical panel, but the large TRE and degree of automation need to be addressed in further work. CONCLUSION: The participating pediatric surgeons and orthopedists were convinced of the clinical value of the interaction between the iUS and the 3D model. Further research is required to improve the surgical accuracy and degree of automation of iUS-based registration systems for the surgical management of pediatric osteosarcoma.

Beyond image defined risk factors (IDRFs): a delphi survey highlighting definition of the surgical complexity index (SCI) in neuroblastoma.

PURPOSE: Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs do not all carry the same weighting in predicting tumor complexity and surgical risk. In this study we aimed to assess and categorize a surgical complexity (Surgical Complexity Index, SCI) in NB resection. METHODS: A panel of 15 surgeons was involved in an electronic Delphi consensus survey to identify and score a set of shared items predictive and/or indicative of surgical complexity, including the number of preoperative IDRFs. A shared agreement included the achievement of at least 75% consensus focused on a single or two close risk categories. RESULTS: After 3 Delphi rounds, agreement was established on 25/27 items (92.6%). A severity score was established for each item ranging from 0 to 3 with an overall SCI range varying from a minimum score of zero to a maximum score of 29 points for any given patient. CONCLUSIONS: A consensus on a SCI to stratify the risks related to neuroblastoma tumor resection was established by the panel experts. This index will now be deployed to critically assign a better severity score to IDRFs involved in NB surgery.

Pleuropulmonary blastoma (PPB) and other DICER1-associated high-grade malignancies are morphologically, genetically and epigenetically related - A comparative study of 4 PPBs and 6 sarcomas.

DICER1-related tumors occur hereditary or sporadically, with high-grade malignancies sharing clinicopathological and (epi)genetic features. We compared 4 pleuropulmonary blastomas (PPBs) and 6 sarcomas by mutation analysis, whole transcriptome sequencing and methylation profiling. 9/10 patients were female. PPB patients were 0-4 years. 3/4 were alive; 2 without disease. One patient died of metastatic disease (median follow-up, 16 months). Sarcoma patients were 16-56 years. Locations included: uterine cervix/corpus (3/1), soft tissue back/shoulder (1) and paravertebral (1). 5/6 patients were alive; 2 developed metastases: intracranial (1) and lung and kidney (1) (median follow-up, 17 months). The deceased patient previously had a PPB and a Sertoli-Leydig cell tumor. Histologically, tumors showed atypical primitive-looking cells with incomplete rhabdomyoblastic differentiation and cartilage (n = 5). Immunohistochemistry demonstrated desmin- (n = 9/10), myogenin- (n = 6/10) and keratin positivity (n = 1/1). Eight cases harbored biallelic DICER1 mutations with confirmed germline mutations in 4 cases. Two cases showed a monoallelic mutation. By RNA expression- and methylation profiling, distinct clustering of our cases was seen demonstrating a close relationship on (epi)genetic level and similarities to embryonal rhabdomyosarcoma. In conclusion, this study shows overlapping morphological, immunohistochemical and (epi)genetic features of PPBs and DICER1-associated high-grade sarcomas, arguing that these neoplasms form a spectrum with a broad clinicopathological range.

Surgical Outcome of Children with a Malignant Liver Tumour in The Netherlands: A Retrospective Consecutive Cohort Study.

Introduction: Six to eight children are diagnosed with a malignant liver tumour yearly in the Netherlands. The majority of these tumours are hepatoblastoma (HB) and hepatocellular carcinoma (HCC), for which radical resection, often in combination with chemotherapy, is the only curative treatment option. We investigated the surgical outcome of children with a malignant liver tumour in a consecutive cohort in the Netherlands. Methods: In this nationwide, retrospective observational study, all patients (age < 18 years) diagnosed with a malignant liver tumour, who underwent partial liver resection or orthotopic liver transplantation (OLT) between January 2014 and April 2021, were included. Children with a malignant liver tumour who were not eligible for surgery were excluded from the analysis. Data regarding tumour characteristics, diagnostics, treatment, complications and survival were collected. Outcomes included major complications (Clavien−Dindo ≥ 3a) within 90 days and disease-free survival. The results of the HB group were compared to those of a historical HB cohort. Results: Twenty-six children were analysed, of whom fourteen (54%) with HB (median age 21.5 months), ten (38%) with HCC (median age 140 months) and one with sarcoma and a CNSET. Thirteen children with HB (93%) and three children with HCC (30%) received neoadjuvant chemotherapy. Partial hepatic resection was possible in 19 patients (12 HB, 6 HCC, and 1 sarcoma), whilst 7 children required OLT (2 HB, 4 HCC, and 1 CNSET). Radical resection (R0, margin ≥ 1.0 mm) was obtained in 24 out of 26 patients, with recurrence only in the patient with CNSET. The mean follow-up was 39.7 months (HB 40 months, HCC 40 months). Major complications occurred in 9 out of 26 patients (35% in all, 4 of 14, 29% for HB). There was no 30- or 90-day mortality, with disease-free survival after surgery of 100% for HB and 80% for HCC, respectively. Results showed a tendency towards a better outcome compared to the historic cohort, but numbers were too small to reach significance. Conclusion: Survival after surgical treatment for malignant liver tumours in the Netherlands is excellent. Severe surgical complications arise in one-third of patients, but most resolve without long-term sequelae and have no impact on long-term survival.

The efficacy of taurolidine containing lock solutions for the prevention of central-venous-catheter-related bloodstream infections: a systematic review and meta-analysis.

The incidence of central venous catheter (CVC)-related bloodstream infections is high in patients requiring a long-term CVC. Therefore, infection prevention is of the utmost importance. The aim of this study was to provide an updated overview of randomized controlled trials (RCTs) comparing the efficacy of taurolidine containing lock solutions (TL) to other lock solutions for the prevention of CVC-related bloodstream infections in all patient populations. On 15th February 2021, PubMed, Embase and The Cochrane Library were searched for RCTs comparing the efficacy of TLs for the prevention of CVC-related bloodstream infections with other lock solutions. Exclusion criteria were non-RCTs, studies describing <10 patients and studies using TLs as treatment. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. A random effects model was used to pool individual study incidence rate ratios (IRRs). Subgroup analyses were performed based on the following factors: CVC indication, comparator lock and bacterial isolates cultured. A total of 14 articles were included in the qualitative synthesis describing 1219 haemodialysis, total parenteral nutrition and oncology patients. The pooled IRR estimated for all patient groups together (nine studies; 918 patients) was 0.30 (95% confidence interval 0.19-0.46), favouring the TLs. Adverse events (10 studies; 867 patients) were mild and scarce. The quality of the evidence was limited due to a high risk of bias and indirectness of evidence. The use of TLs might be promising for the prevention of CVC-related bloodstream infections. Large-scale RCTs are needed to draw firm conclusions on the efficacy of TLs.

Neuroblastoma between 1990 and 2014 in the Netherlands: Increased incidence and improved survival of high-risk neuroblastoma.

PURPOSE: Long-term trends in neuroblastoma incidence and survival in unscreened populations are unknown. We explored trends in incidence, stage at diagnosis, treatment and survival of neuroblastoma in the Netherlands from 1990 to 2014. METHODS: The Netherlands Cancer Registry provided data on all patients aged <18 years diagnosed with a neuroblastoma. Trends in incidence and stage were evaluated by calculating the average annual percentage change (AAPC). Univariate and multivariable survival analyses were performed for stage 4 disease to test whether changes in treatment are associated with survival. RESULTS: Of the 593 newly diagnosed neuroblastoma cases, 45% was <18 months of age at diagnosis and 52% had stage 4 disease. The age-standardized incidence rate for stage 4 disease increased at all ages from 3.2 to 5.3 per million children per year (AAPC + 2.9%, p < .01). This increase was solely for patients ≥18 months old (3.0-5.4; AAPC +3.3%, p = .01). Five-year OS of all patients increased from 44 ± 5% to 61 ± 4% from 1990 to 2014 (p < .01) and from 19 ± 6% to 44 ± 6% (p < .01) for patients with stage 4 disease. Multivariable analysis revealed that high-dose chemotherapy followed by autologous stem cell rescue and anti-GD2-based immunotherapy were associated with this survival increase (HR 0.46, p < .01 and HR 0.37, p < .01, respectively). CONCLUSION: Incidence of stage 4 neuroblastoma increased exclusively in patients aged ≥18 months since 1990, whereas the incidence of other stages remained stable. The 5-year OS of stage 4 patients improved, mostly due to the introduction of high-dose chemotherapy followed by stem cell rescue and immunotherapy.

RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia.

RAS pathway mutations have been linked to relapse and chemotherapy resistance in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive data on the frequency and prognostic value of subclonal mutations in well-defined subgroups using highly sensitive and quantitative methods are lacking. Targeted deep sequencing of 13 RAS pathway genes was performed in 461 pediatric BCP-ALL cases at initial diagnosis and in 19 diagnosis-relapse pairs. Mutations were present in 44.2% of patients, with 24.1% carrying a clonal mutation. Mutation frequencies were highest in high hyperdiploid, infant t(4;11)-rearranged, BCR-ABL1-like and B-other cases (50-70%), whereas mutations were less frequent in ETV6-RUNX1-rearranged, and rare in TCF3-PBX1- and BCR-ABL1-rearranged cases (27-4%). RAS pathway-mutated cells were more resistant to prednisolone and vincristine ex vivo. Clonal, but not subclonal, mutations were linked to unfavorable outcome in standard- and high-risk-treated patients. At relapse, most RAS pathway mutations were clonal (9 of 10). RAS mutant cells were sensitive to the MEK inhibitor trametinib ex vivo, and trametinib sensitized resistant cells to prednisolone. We conclude that RAS pathway mutations are frequent, and that clonal, but not subclonal, mutations are associated with unfavorable risk parameters in newly diagnosed pediatric BCP-ALL. These mutations may designate patients eligible for MEK inhibitor treatment.

Biogeographical factors affecting the distribution of stream salamanders on the Cumberland Plateau, USA.

Geophysical and climate conditions play an important role in the distribution of organisms at both fine and broad scales. Headwater streams integrate changes at broad geographical scales and serve as important regions of nutrient processing and support high biodiversity. Stream salamanders are important members of headwater aquatic communities as both predators and prey. Combined with their biphasic life histories and physiological requirements, stream amphibians may serve as indicators for headwater stream conditions. We surveyed 50 streams for salamander occupancy, across eight counties of the southern Cumberland Plateau in Tennessee for which we are unaware of any stream amphibian distribution data. Our objective was to determine what variables best-predicted stream amphibian occupancy among species with variable life histories and habitat needs. Models were generated to determine the effects of elevation, catchment forest cover, and total catchment size as indicators of stream condition. We found species showed no significant responses to forest cover. Though forest cover has previously been the primary predictor of stream amphibian occupancy in streams across the United States, stream amphibian occupancy of the southern Cumberland Plateau was most closely associated with elevation and catchment size. Thus, the unique topography of the southern Cumberland Plateau may instead be the more important factor driving occupancy patterns. Despite limited evidence in this study for negative human impacts on salamander occupancy, low occupancy and abundance relative to other ecoregions suggests either poor quality habitat or large historic impacts. Developing a more comprehensive understanding of regional stream salamander occupancy patterns is necessary to ensure effective management and habitat conservation in a region with limited description of stream ecology.

Risk factors for the displacement of fractures of both bones of the forearm in children.

Forearm fractures in children have a tendency to displace in a cast leading to malunion with reduced functional and cosmetic results. In order to identify risk factors for displacement, a total of 247 conservatively treated fractures of the forearm in 246 children with a mean age of 7.3 years (sd 3.2; 0.9 to 14.9) were included in a prospective multicentre study. Multivariate logistic regression analyses were performed to assess risk factors for displacement of reduced or non-reduced fractures in the cast. Displacement occurred in 73 patients (29.6%), of which 65 (89.0%) were in above-elbow casts. The mean time between the injury and displacement was 22.7 days (0 to 59). The independent factors found to significantly increase the risk of displacement were a fracture of the non-dominant arm (p = 0.024), a complete fracture (p = 0.040), a fracture with translation of the ulna on lateral radiographs (p = 0.014) and shortening of the fracture (p = 0.019). Fractures of both forearm bones in children have a strong tendency to displace even in an above-elbow cast. Severe fractures of the non-dominant arm are at highest risk for displacement. Radiographs at set times during treatment might identify early displacement, which should be treated before malunion occurs, especially in older children with less potential for remodelling.

Postmortem biopsy to obtain lung tissue in congenital diaphragmatic hernia.

BACKGROUND: The accrual of human tissues from autopsies for diagnostic and translational research has decreased significantly over the last decades. OBJECTIVES: The objective of this study was to evaluate our experience with lung biopsy through a minithoracotomy as an alternative for obtaining postmortem tissue when full autopsy is refused in congenital diaphragmatic hernia (CDH) patients. METHODS: Within 2 h of death we routinely asked parents for permission to perform an autopsy. Starting in 2001, parents who refused autopsy were asked permission for a postmortem lung biopsy. Pathology autopsy and biopsy reports were compared to clinical records. RESULTS: Between 2001 and 2009, 46 patients died from CDH. Permission for autopsy was granted in 5 patients (11%). Of the remaining 41 patients, the parents of 15 (33%) agreed to postmortem lung biopsy. In all cases, additional findings were reported from the autopsy or biopsy, without changing the originally reported cause of death. In 1 case, we isolated fibroblasts from the lung biopsy using standardized cell culture techniques. Parents were able to take their child home with a minimal delay following biopsy. CONCLUSIONS: Parents refusing a full autopsy frequently agree to postmortem organ biopsy. This approach should therefore be considered as a valuable alternative, when permission for full autopsy is declined, for obtaining human tissues for both diagnostic and research purposes and is potentially applicable to other anomalies.

The pharmacokinetics and safety of twice daily i.v. BU during conditioning in pediatric allo-SCT recipients.

Intravenous BU divided four times daily (q6 h) has been shown to be safe and effective in pediatric allo-SCT recipients. Though less frequent dosing is desirable, pharmacokinetic (PK) data on twice daily (q12 h) i.v. BU administration in pediatric allo-SCT recipients is limited. We prospectively examined the PK results in a cohort of pediatric allo-SCT recipients receiving i.v. BU q12 h as part of conditioning before allo-SCT. BU levels were obtained after the first dose of conditioning. PK parameter analysis (n=49) yielded the following 95% confidence intervals (CI95): weight-normalized volume of distribution: 0.65-0.73 L/kg; t(1/2): 122-147 min; weight-normalized clearance (CL(n)): 3.4-4.3 mL/min/kg; and area under the curve: 1835-2180 mmol × min/L. From these results, a steady state concentration was calculated with CI95 between 628-746 ng/mL. Comparison between recipients ≤4 vs >4 years old revealed significant differences in t(1/2) (mean: 115 vs 146 min, P=0.008) and CL(n) (mean: 4.4 vs 3.5 mL/min/kg, P=0.038). Intravenous BU q12 h had a comparable PK to i.v. BU q6 h PK seen in the literature, and in pediatric allo-SCT recipients, is a feasible, attractive alternative to i.v. q6h dosing.

Early hospital discharge of infants born to group B streptococci-positive mothers: a decision analysis.

OBJECTIVE: To compare the cost-effectiveness of an additional 24-hour inpatient observation for asymptomatic term neonates born to group B streptococcus (GBS)-colonised mothers with adequate intrapartum antibiotic prophylaxis (IAP) after an initial 24-hour in-hospital observation. DESIGN: Cost-effectiveness analysis from a societal perspective. SETTING: United States. POPULATION: Asymptomatic term neonates born to GBS-colonised mothers with IAP after an initial 24-hour in-hospital observation. METHODS: Monte Carlo simulation for a decision tree model incorporating the following chance events: development of GBS sepsis during the second 24 hours of life, development of GBS sepsis between 48 hours and 7 days of life, prompt versus delayed treatment for sepsis, neonatal mortality and long-term health sequelae. MAIN OUTCOME MEASURES: Expected cost and quality-adjusted life years (QALYs), Incremental cost-effectiveness ratio (ICER). RESULTS: Delayed, versus early, hospital discharge results in similar mean expected QALYs, but substantially higher expected cost. The mean difference in QALY is 0.00016 (95% CI 0.00005-0.00040), whereas the mean difference in cost is $1170.96 (95% CI $750.13-1584.32). The ICER is estimated to be $9,771,520.87 per QALY (95% CI $2,573,139.89-24,407,017.82). The proportion of early-onset GBS that develops during the second 24 hours of life, the cost of 24 hours of inpatient observation, and the probability of long-term sequelae following prompt versus delayed treatment play important roles in determining the cost-effectiveness of delayed hospital discharge. CONCLUSION: Cost-effectiveness analysis suggests that with adequate IAP, discharging asymptomatic term neonates to home after 24 hours is the preferred approach compared with 48 hours inpatient observation.

Congenital diaphragmatic hernia: still a moving target.

The primary therapeutic target for congenital diaphragmatic hernia (CDH) patients has shifted from emergency surgical repair towards a non-operative emergency of the newborn treated by interdisciplinary teams. The increased understanding of the epidemiological and pathophysiological aspects of CDH have led to an improved knowledge and application of prenatal diagnosis, postnatal ventilation strategies, treatment of associated pulmonary hypertension and the role of extracorporeal membrane oxygenation therapy. In the surgical field, the perspectives have changed with delayed CDH repair, the introduction of minimally invasive surgery and use of prosthetic material for closure of large defects. With decreased mortality, long term multi-organ morbidity has increased in some survivors. In the near future, randomized controlled trials on different aspects of therapy will determine evidence-based optimal care.

Pericardial effusion post-SCT in pediatric recipients with signs and/or symptoms of cardiac disease.

The objective of this study was to assess the incidence, risk factors, outcome and impact on OS of pericardial effusion (PEF) in a cohort of 156 pediatric SCT recipients. The mean age was 8.15±6.25 years. In all, 74% of the patients had malignant disease and 35% of the patients received autologous stem cell grafts. Twenty-three subjects developed effusion at 2.75±3.54 months after SCT. The overall probability of developing a PEF after SCT was 16.9%. In the multivariate analysis of risk factors associated with time to PEF, increased age, allogeneic risk status and conditioning type, were all significant factors. In a multivariate analysis of time to death, PEF, CMV status and risk status were all independent risk factors. PEF, however, had the highest HR of 3.334. Of the 23 patients with PEF, 19 died (82.6%); however, none died as a direct result of pericardial tamponade. In summary, our results suggest that PEF is a significant risk factor for post transplant mortality. These results suggest a need for more frequent evaluation and monitoring for development of PEF. Studies are needed to determine the etiology of, and new therapeutic strategies for, PEF in the post-SCT population.

A pilot study of reduced toxicity conditioning with BU, fludarabine and alemtuzumab before the allogeneic hematopoietic SCT in children and adolescents.

We report the results of a pilot study of a BU-fludarabine-alemtuzumab (BFA)-reduced toxicity conditioning (RTC) followed by allogeneic hematopoietic SCT (AlloHSCT) in 12 children and adolescents (<21 years) with malignant and non-malignant diseases. Stem cell sources were: two unrelated cord blood, one unrelated BM, two related and seven unrelated PBSC. Positive CD34 selection was performed in five unrelated PBSC grafts. RCT was carried out with BFA, and GVHD prophylaxis was FK506 and mycophenolate mofetil. The median time for neutrophil and platelet engraftment was 16 and 31 days, respectively. The P of developing ≥ grade II, ≥ grade III aGVHD and cGVHD was 41.6, 25 and 9%, respectively. Only 1 out of 12 developed ≥ grade III toxicity. There was one primary and no secondary graft failure. Mixed donor chimerism on day 100 and 1 year was median 99 and 96%, respectively; ≥ 90% of recipients achieved ≥ 80% donor chimerism. The 3-year overall survival (OS) in all patients was 91.7 ± 8% (100% for malignant vs. 80% for non-malignant diseases, ns). In all, 11 (91%) patients remain alive at median 2.8 (0.3-6.8) years. RTC followed by AlloHSCT, based on BFA conditioning, is feasible and tolerable in children and adolescents, and results in prompt achievement of durable mixed donor chimerism and excellent OS.

Self-limiting sternal tumors of childhood (SELSTOC).

BACKGROUND: Because a sternal mass is often alarming, it is important to identify the clinical features of benign processes. PROCEDURE: Data on clinical presentation, diagnostics, treatment and outcome of pediatric patients presenting with a sternal tumor between 2001 and 2009 were collected from medical records. RESULTS: Among the 1,700 children who were referred to our pediatric-oncology center, 14 presented with a rapidly growing sternal mass. All patients (10 males) were Caucasian and median age was 16 (range: 7-50) months. Reported symptoms were local pain (n = 7) and/or raised body temperature (n = 5). No major preceding traumas were reported. Physical examination revealed solid tumors with a median diameter of 3 (range: 1-4.5) cm in a pre-sternal/para-sternal location. Half of the patients showed red/blue discoloration of the skin. On radiology, dumbbell-shaped lesions extended to the area behind the sternal bone, involving the cartilage, leading to increased distance between ossification centers. Histopathology at diagnosis was available from five patients and showed aspecific chronic or acute inflammation (n = 4) and a reactive osteochondromatous lesion (n = 1). Laboratory infection parameters were not/only slightly raised and microbiologic cultures were negative in all patients. All tumors decreased in size within 1 month, in both patients with and without antibiotics. On physical examination the tumors disappeared within 6 months. CONCLUSIONS: This study reports 14 young children with a rapidly growing sternal mass due to aseptic inflammation, that we named self-limiting sternal tumor of childhood (SELSTOC). To prevent invasive diagnostic interventions and unnecessary treatment, we advocate a wait-and-see approach with close follow-up in the first weeks.