Retrospektive Analyse der Strahlenexposition thorakaler CT bei pädiatrischen Patienten unter klinischen Bedingungen mittels eines Drittgeneration Dual-Source-Scanners (Siemens, Force) und Identifikation möglicher Faktoren, die eine Sub-mSv-Aufnahme erschweren.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) has become a well-established treatment option for many patients suffering from malignant and non-malignant diseases. In the past decade, high-resolution HLA-typing, remission surveillance, pre-emptive immune intervention, and standardisation in supportive care measures have substantially improved transplant outcomes. This retrospective study evaluated transplant procedures in 162 paediatric patients with acute lymphoblastic leukaemia ( n = 124) or acute myeloid leukaemia ( n = 38) who received their first alloHSCT in our institution over an 11-year period. We observed a significant reduction in risk of non-relapse mortality (NRM) over time (HR = 0.34, 95% CI 0.12–0.98; P = 0.05), the 4-year NRM estimate decreased from 20% in 2005–2008 to 7% in 2012–2016 ( P = 0.02) and an increase in survival after relapse. There was no significant difference in patients who received a graft from a sibling, haplo, or an unrelated donor with regard to their overall survival ( P = 0.45), event-free survival ( P = 0.61), and non-relapse mortality ( P = 0.19). Our data suggest that a specific transplant infrastructure with a highly experienced team in an accredited transplant centre likely contributes to better transplant outcomes for acute leukaemia patients in complete remission regardless of donor type.

Kurzfassung: Die Computertomographie (CT) ist ein wichtiges und ein sich schnell entwickelndes Diagnosewerkzeug in der heutigen Medizin. Mehrere modellbasierte Schätzungen, die auf Daten von Atombombenüberlebenden beruhten, verursachten aufgrund der Exposition gegenüber ionisierender Strahlung Bedenken hinsichtlich möglicher Krebsrisiken nach pädiatrischen CT-Untersuchungen. Daraufhin wurden ab 2007 epidemiologische Studien geplant, welche untersuchen sollten, ob eine niedrige bis mittlere Strahlendosis von CTs Krebs verursachen kann. Ab 2012 wurden erste Ergebnisse aus diesen Studien von Großbritannien, Australien und Taiwan publiziert, welche erhöhte Risiken für Leukämie und ZNS-Tumore berichteten. Während diese Studien für mehrere methodische Beschränkungen kritisiert wurden, versuchen jüngste Analysen aus Frankreich, Deutschland und Großbritannien, diese Kritiken zu berücksichtigen. Hierbei wurde vor allem auf „reverse-causation“, die CT wurde durch frühe Anzeichen eines viel später diagnostizierten Krebs verursacht, und "confounding by indication", Krebserkrankung wurde möglicherweise durch eine andere Krankheit verursacht, eingegangen. Eine weitere Schwachstelle aller momentanen Studien ist eine unzureichende Schätzung der Organdosis exponierter Personen. Alle Studien unternehmen momentan große Anstrengungen zur Überwindung der ungenauen Dosimetrie. Internationale Pooling-Studien sind im Gange (EPI-CT, internationales CT-Pooling-Projekt). Laufende internationale Studien werden dazu beitragen, eine bessere Risikoabschätzung zu erhalten, wenn länderspezifische Aspekte berücksichtigt werden können. Weitere Studien benötigen eine genauere Dosimetrie und Messfehler müssen berücksichtigt werden.

Fragestellung: Bei Patienten mit malignen Erkrankungen während und nach Anthrazyklintherapie besteht die Gefahr einer toxischen Kardiomyopathie. Inwieweit schon subklinische Veränderungen im Myokard zuverlässig bei den neuen Echo-Methoden wie 3D Strain erfasst werden, ist der Gegenstand dieser prospektiven Studie.

Monitoring of minimal residual disease (MRD) or chimerism may help guide pre-emptive immunotherapy (IT) with a view to preventing relapse in childhood acute lymphoblastic leukemia (ALL) after transplantation. Patients with ALL who consecutively underwent transplantation in Frankfurt/Main, Germany between January 1, 2005 and July 1, 2014 were included in this retrospective study. Chimerism monitoring was performed in all, and MRD assessment was performed in 58 of 89 patients. IT was guided in 19 of 24 patients with mixed chimerism (MC) and MRD and by MRD only in another 4 patients with complete chimerism (CC). The 3-year probabilities of event-free survival (EFS) were.69.06 for the cohort without IT and.69.10 for IT patients. Incidences of relapse (CIR) and treatment-related mortality (CITRM) were equally distributed between both cohorts (without.IT: 3-year CIR,.21.05, 3-year CITRM,.10.04; IT patients: 3-year CIR,.18.09, 3-year CITRM.13.07). Accordingly, 3-year EFS and 3-year CIR were similar in CC and MC patients with IT, whereas MC patients without IT experienced relapse. IT was neither associated with an enhanced immune recovery nor an increased risk for acute graft-versus-host disease. Relapse prevention by IT in patients at risk may lead to the same favorable outcome as found in CC and MRD-negative-patients. This underlines the importance of excellent MRD and chimerism monitoring after transplantation as the basis for IT to improve survival in childhood ALL. (C) 2017 American Society for Blood and Marrow Transplantation.

Therapy for post-transplant relapse of paediatric ALL is limited. Standardised curative approaches are not available. We hereby describe our local procedure in this life-threatening situation. A total of 101 ALL patients received their first allogeneic stem cell transplantation (SCT) in our institution. After relapse, our primary therapeutic goal was to cure the patient with high-dose chemotherapy or specific immunotherapy (HDCHT/SIT) followed by a second SCT from a haploidentical donor (transplant approach). If this was not feasible, low-dose chemotherapy and donor lymphocyte infusions (LDCHT+DLI) were offered (non-transplant approach). A total of 23 patients suffered a post-transplant relapse. Eight patients received HDCHT/SIT, followed by haploidentical SCT in 7/8. Ten received LDCHT+DLI. The eight patients treated with a second transplant and the ten treated with the non-transplant approach had a 4-year overall survival of 56% and 40%, respectively (P = 0.232). Prerequisites for successful treatment of post-transplant relapse by either a second transplant or experimental non-transplant approaches are good clinical condition and the capacity to achieve haematological remission by the induction treatment element.

Mixed chimerism (MC) and MRD strongly predict relapse in children with ALL after allo-SCT. Pre-emptive immunotherapy (IT), e.g. withdrawal of immunosuppression (WD-IS) or DLI can prevent impending relapse. In this study we retrospectively analyzed chimerism and MRD monitoring and the effect of pre-emptive IT.

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 14, Issue 1 p. 59-61 Clinical Letter Multiple Granularzelltumoren und primitiver neuroektodermaler Tumor (PNET) – Ein syndromaler Zusammenhang? Sandra Mauer, Sandra Mauer Universitätsklinikum des Saarlandes, Klinik für Dermatologie, Venerologie und Allergologie, Homburg/SaarSearch for more papers by this authorClaudia Pföhler, Claudia Pföhler Universitätsklinikum des Saarlandes, Klinik für Dermatologie, Venerologie und Allergologie, Homburg/SaarSearch for more papers by this authorYoo Jin Kim, Yoo Jin Kim Universitätsklinikum des Saarlandes, Institut für allgemeine und spezielle Pathologie, Homburg/SaarSearch for more papers by this authorThomas Krenn, Thomas Krenn Universitätsklinikum des Saarlandes, Klinik für pädiatrische Onkologie und Hämatologie, Homburg/SaarSearch for more papers by this authorSabine Heine, Sabine Heine Universitätsklinikum des Saarlandes, Klinik für pädiatrische Onkologie und Hämatologie, Homburg/SaarSearch for more papers by this authorThomas Vogt, Thomas Vogt Universitätsklinikum des Saarlandes, Klinik für Dermatologie, Venerologie und Allergologie, Homburg/SaarSearch for more papers by this authorCornelia Sigrid Lissi Müller, Corresponding Author Cornelia Sigrid Lissi Müller Universitätsklinikum des Saarlandes, Klinik für Dermatologie, Venerologie und Allergologie, Homburg/SaarSearch for more papers by this author Sandra Mauer, Sandra Mauer Universitätsklinikum des Saarlandes, Klinik für Dermatologie, Venerologie und Allergologie, Homburg/SaarSearch for more papers by this authorClaudia Pföhler, Claudia Pföhler Universitätsklinikum des Saarlandes, Klinik für Dermatologie, Venerologie und Allergologie, Homburg/SaarSearch for more papers by this authorYoo Jin Kim, Yoo Jin Kim Universitätsklinikum des Saarlandes, Institut für allgemeine und spezielle Pathologie, Homburg/SaarSearch for more papers by this authorThomas Krenn, Thomas Krenn Universitätsklinikum des Saarlandes, Klinik für pädiatrische Onkologie und Hämatologie, Homburg/SaarSearch for more papers by this authorSabine Heine, Sabine Heine Universitätsklinikum des Saarlandes, Klinik für pädiatrische Onkologie und Hämatologie, Homburg/SaarSearch for more papers by this authorThomas Vogt, Thomas Vogt Universitätsklinikum des Saarlandes, Klinik für Dermatologie, Venerologie und Allergologie, Homburg/SaarSearch for more papers by this authorCornelia Sigrid Lissi Müller, Corresponding Author Cornelia Sigrid Lissi Müller Universitätsklinikum des Saarlandes, Klinik für Dermatologie, Venerologie und Allergologie, Homburg/SaarSearch for more papers by this author First published: 29 December 2015 https://doi.org/10.1111/ddg.20_12683AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume14, Issue1January 2016Pages 59-61 RelatedInformation

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 14, Issue 1 p. 59-61 Clinical Letter Multiple granular cell tumors and primitive neuroectodermal tumors (PNETs) – is there a syndromic relationship? Sandra Mauer, Sandra Mauer Saarland University Hospital, Department of Dermatology, Venereology, and Allergology, Homburg/Saar, GermanySearch for more papers by this authorClaudia Pföhler, Claudia Pföhler Saarland University Hospital, Department of Dermatology, Venereology, and Allergology, Homburg/Saar, GermanySearch for more papers by this authorYoo Jin Kim, Yoo Jin Kim Saarland University Hospital, Institute of General and Special Pathology, Homburg/Saar, GermanySearch for more papers by this authorThomas Krenn, Thomas Krenn Saarland University Hospital, Department of Pediatric Oncology and Hematology, Homburg/Saar, GermanySearch for more papers by this authorSabine Heine, Sabine Heine Saarland University Hospital, Department of Pediatric Oncology and Hematology, Homburg/Saar, GermanySearch for more papers by this authorThomas Vogt, Thomas Vogt Saarland University Hospital, Department of Dermatology, Venereology, and Allergology, Homburg/Saar, GermanySearch for more papers by this authorCornelia Sigrid Lissi Müller, Corresponding Author Cornelia Sigrid Lissi Müller Saarland University Hospital, Department of Dermatology, Venereology, and Allergology, Homburg/Saar, Germany Assoc. Prof. Cornelia Müller, M.D. Department of Dermatology, Venereology, and Allergology Saarland University Hospital Kirrberger Straße 66421 Homburg/Saar Germany E-mail: [email protected]Search for more papers by this author Sandra Mauer, Sandra Mauer Saarland University Hospital, Department of Dermatology, Venereology, and Allergology, Homburg/Saar, GermanySearch for more papers by this authorClaudia Pföhler, Claudia Pföhler Saarland University Hospital, Department of Dermatology, Venereology, and Allergology, Homburg/Saar, GermanySearch for more papers by this authorYoo Jin Kim, Yoo Jin Kim Saarland University Hospital, Institute of General and Special Pathology, Homburg/Saar, GermanySearch for more papers by this authorThomas Krenn, Thomas Krenn Saarland University Hospital, Department of Pediatric Oncology and Hematology, Homburg/Saar, GermanySearch for more papers by this authorSabine Heine, Sabine Heine Saarland University Hospital, Department of Pediatric Oncology and Hematology, Homburg/Saar, GermanySearch for more papers by this authorThomas Vogt, Thomas Vogt Saarland University Hospital, Department of Dermatology, Venereology, and Allergology, Homburg/Saar, GermanySearch for more papers by this authorCornelia Sigrid Lissi Müller, Corresponding Author Cornelia Sigrid Lissi Müller Saarland University Hospital, Department of Dermatology, Venereology, and Allergology, Homburg/Saar, Germany Assoc. Prof. Cornelia Müller, M.D. Department of Dermatology, Venereology, and Allergology Saarland University Hospital Kirrberger Straße 66421 Homburg/Saar Germany E-mail: [email protected]Search for more papers by this author First published: 04 December 2015 https://doi.org/10.1111/ddg.12683AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Volume14, Issue1January 2016Pages 59-61 RelatedInformation

Abstract Introduction: Mixed chimerism (MC) and minimal residual disease (MRD) strongly predict risk for relapse in children with acute lymphoblastic leukemia (ALL) following allogeneic stem cell transplantation (allo-SCT). Preemptive immunotherapy (IT), e.g. withdrawal of immunosuppression (WD-IS) or donor lymphocyte infusion (DLI) guided by chimerism and MRD monitoring can prevent impending relapse in allo-SCT recipients. In this study we retrospectively analyzed chimerism and MRD monitoring and the effect of preemptive IT in all pts undergoing allo-SCT for ALL in our institution. Patients: Between January 2005 and July 2014, a total of 89 children and adolescents (median age 11.5; range 2.2-26.0 years) with ALL (pB-ALL, n=63; T-ALL, n=20; biphenotypic/bilinear ALL, n=6) were transplanted in our center after remission induction treatment. 47 pts were in first, 26 pts were in second, 15 pts were in third, and 1 pt was in fourth complete remission (CR) at time of transplant. 18 pts received grafts from matched sibling donors (MSD), 61 pts from matched unrelated donors (MUD), and 10 pts were grafted from a haploidentical parent. Pts who received their graft from a matched donor (n=79) all underwent a fully myeloablative conditioning regimen consisting of TBI (12 Gy) and etoposide. Pts who were grafted from a haploidentical donor were prepared with fludarabine, thiotepa and melphalane. Methods: Serial and semi quantitative analyses of post-transplant hematopoietic chimerism in peripheral blood were performed weekly until day 200 and monthly thereafter. Bone marrow analyses were done at days +30, +60, +90, +180 and +365 post-transplant. Thereby, MRD was assessed in 56 pts, whereas no diagnostic material was available in 33 pts. Standardized quantification of MRD was performed according to the guidelines of the Euro-MRD-Group. All patients should receive preemptive IT if they develop MC after day +28. Results: 64/89 pts (72%) showed complete chimerism (CC) in all follow-up analyses, and 25/89 pts (28%) developed MC although all pts received a fully myeloablative conditioning regimen. From 56 pts in whom MRD could be assessed, 40 pts remained MRD negative and 16 developed MRD positivity after transplantation. IT (WD-IS, n=12; DLI, n=14) was initiated based on chimerism analysis in 22/25 pts with MC, and was guided by MRD detection in 4 pts. For the total cohort of pts, probability of event free (pEFS) and overall survival (pOS) were 0.67 and 0.77, respectively. Furthermore, cumulative incidence of treatment related mortality (CI-TRM) and relapse (CI-relapse) were 0.11 and 0.24 for all pts. Chimerism: pEFS was 0.74 in CC-pts and 0.51 in MC-pts (p<0.032). 22/25 MC-pts received pre-emptive IT resulting in a pEFS of 0.58. Due to rapid progression of their disease IT was not initiated in 3/25 MC-pts. All MC-pts without IT relapsed, and in part received further treatment. While CI-TRM remained low (0.10 for CC resp. 0.12 for MC, p>0.68) in both groups, CI-relapse was 0.17 in CC- and 0.41 in MC-pts (p<0.021). MRD: Besides MC, MRD level post-transplant emerged as poor prognostic factor. Pts were grouped according to their highest MRD value post-transplant in MRD negative, low positive (<10E-4), and high positive (>10E-4) pts. pEFS and pOS were 0.82 and 0.95 in MRD negative (n=40), 0.56 and 0.88 in low level MRD (n=8), and 0.25 and 0.25 in high level MRD (n=8) positive pts (p<0.001). CI-relapse was 0.14 in MRD negative, 0.36 in MRD low, and 0.75 in MRD high positive pts (p<0.001), while CI-TRM between these groups remained low (0.05 for MRD negative, 0.13 for MRD low and 0.00 for MRD high, p>0.55). Other risk factors: Furthermore, remission status at the time of transplant influenced relapse rate. CI-relapse was 0.16 in CR1, 0.26 in CR2, and 0.45 in CR>2 pts (p<0.025). Differences in pEFS, pOS and CI-TRM among CR1, CR2, and CR>2 pts were not statistically significant. Multivariate analysis: Multivariate analysis for pEFS also indicated that MC and high level MRD were independent poor prognostic factors (MC, p<0.049, RR 3.16 and high level MRD, p<0.022, RR 3.99), while remission status before transplantation, ALL lineage, donor type, graft source, T cell depletion or sex showed no significant influence. Conclusion: Our results show that analysis of chimerism and MRD allow the prediction of impending relapse in virtually all children and adolescents transplanted for ALL and that preemptive IT can improve outcome in these high-risk pts. Disclosures No relevant conflicts of interest to declare.

Background: Preventive approaches (including those related to care of long term central venous catheters, CVADs) and the incidence of bloodstream infections (BSI) in 2 German university affiliated paediatric oncology units.Patients and Methods: Non-interventional prospective observational study using the Oncoped surveillance module.Results: Center A included 85 patients in 31 months and Center B 84 patients in 21 months. The populations did not differ in terms of age, gender, malignancy and disease status (first illness vs. relapse). Center A used ports (46%) and 2 different Broviac catheters (54%), in Center B nearly all patients with a CVAD had Broviacs (96%). 30 BSI (24 patients) were diagnosed in Centre A and 28 BSI (22 patients) in Center B. Patients with relapsed malignancy experienced more BSI (51.4% vs. 20.9%; p=0.001). Incidence rates were significantly lower in Center A (3.47 vs. 7.93 BSI/1000 CVAD days; p=0.037). Poisson regression analysis revealed a significant lower incidence density (BSI/100 inpatient clays) for all BSI in Center A (RR 0.47 CI95 0.27-0.81, p=0.006). Overall, 52% of all pathogens detected in blood cultures in Center A were Gram-positive (57% in Center B) and 48% Gram-negative (43 in Center B). One ALL patient without a CVAD died due to overwhelming sepsis caused by an ESBL-producing E. cloacae isolate.Conclusion: Paediatric cancer treatment centers differ substantially in regard to management of CVADs and in other preventive strategies. The most important use of local surveillance data is longitudinal internal assessment in close cooperation with microbiology and hospital hygiene experts.

Allogeneic stem cell transplantation has become an important option in the curative treatment of many patients with malignant and non-malignant systemic diseases. Non-availability of HLA identical donors can limit access to this life-saving treatment, especially in ethnic minority patients, for whom identical donors are often not available [1,2]. For many years, a central aim has been the development of stem cell transplantation across the HLA barrier and the use of haploidentical parents as stem cell donors. Such an approach will allow allogeneic transplantation of all patients in need. During the past years, it has become possible to optimize in vitro graft manipulation procedures making this transplant procedure safer and more efficient. Therefore this haploidentical transplantation procedure can now serve as a basis for further cellular immunotherapy in the treatment of malignant and non-malignant diseases. (C) 2011 Elsevier Ltd. All rights reserved.

Einleitung: Die Dissektion der A. vertebralis ist eine insgesamt seltene, jedoch im Kindesalter neben kardialen Ursachen wichtige Differentialdiagnose bei Schlaganfällen im hinteren Stromgebiet. Neben offensichtlichen Traumata im Hals- bzw. Wirbelsäulenbereich sind mögliche Ursache unter anderem Erkrankungen des Bindegewebes, Vaskulitiden und Stoffwechselerkrankungen. Ein Großteil der Dissektionen ist idiopathisch.

A 15-year-old adolescent boy with autosomal recessive agammaglobulinemia underwent endoscopy because of unexplained growth failure and malnutrition. Esophagogastroduodenoscopy revealed antropyloric stenosis, and a biopsy showed an invasive gastric adenocarcinoma. Chronic atrophic corpus gastritis type A and Helicobacter pylori were also identified. Abdominal magnetic resonance imaging confirmed the stenosis resulting from a semicircular intramural tumor without obvious local or distant metastatic spread. Gastrectomy with an extended lymphadenectomy was performed. Esophagoduodenal continuity was restored by an interposed jejunal parallel pouch developed from the first jejunal loop. Oral feeding was supplemented by parenteral nutrition via a Broviac catheter, and the patient is well 4 months later. Several cases of gastric cancer have been reported in children with hereditary agammaglobulinemia. Thus, endoscopy is mandatory in such patients with gastrointestinal symptoms to identify and treat tumors before metastasis occurs. Total gastrectomy, extended lymphadenectomy, and reconstruction using a jejunal reservoir with maintenance of duodenal continuity should be considered.