Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations.

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations

Ortsnahe Koordinierung Zweiter Zwischenbericht der wissenschaftlichen Begleitforschung

Der Zwischenbericht fasst den Stand der Projektentwicklung zu dem Vorhaben 'Ortsnahe Koordinierung der gesundheitlichen und sozialen Versorgung' fuer den Zeitraum 1996-1997 zusammen. Die Zielsetzungen des Projektes, das in 28 Modellkommunen Nordrhein-Westfalens stattfindet, werden dargestellt und die bisherigen Ergebnisse evaluiert. Die empirische Basis bilden standardisierte Dokumentationen von 102 Sitzungen der Runden Tische sowie 472 Sitzungen der Arbeitsgruppen, schriftliche Befragungen von ca. 1200 Gremienteilnehmern, strukturierte Interviews mit den Projektbeteiligten sowie eine Inhaltsanalyse der Handlungsempfehlungen. Bezueglich der gesundheitspolitisch zentralen Frage nach den Auswirkungen des Modellvorhabens auf die gesundheitliche und soziale Versorgung werden positive Entwicklungen konstatiert, obwohl eine verallgemeinerungswuerdige Bewertung noch nicht vorgenommen werden kann. (pra)Available from UuStB Koeln(38)-990107718 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT

Patients with hypomorphic mutations in RAG1 and RAG2 genes present as either Omenn syndrome or atypical combined immunodeficiency (CID) with a wide phenotypic range. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but data are scarce. We report on a worldwide cohort of 60 patients with hypomorphic RAG variants who underwent HSCT, 78% of whom experienced infections (29% active at HSCT), 72% autoimmunity and 18% granulomas pre-transplant. These complications were frequently associated with organ damage. Eight individuals (13%) were diagnosed by newborn screening or family history. HSCT was performed at a median of 3.4 years (range 0.3 - 42.9 years) from matched unrelated donors, matched sibling or matched family donors or mismatched donors (MMFD) in 48%, 22% and 30% of the patients, respectively. Grafts were T-cell depleted in 15 cases (25%). Overall survival at 1 and 4 years was 77.5 and 67.5% (median follow-up 39 months). Infection was the main cause of death. In univariable analysis, active infection, organ damage pre-HSCT, T-cell depletion of the graft and transplant from a MMFD were predictive of worse outcome, while organ damage and T-cell depletion remained significant in multivariable analysis (HR=6.01, HR=8.46, respectively). All patients diagnosed by newborn screening or family history survived. Cumulative incidences (CI) of acute and chronic GvHD were 35% and 22% respectively. CI of new-onset autoimmunity was 15%. Immune reconstitution, particularly recovery of naïve CD4+ T-cells was faster and more robust in patients transplanted before 3.5 years and without organ damage. These findings support the indication for early transplantation

Using death certificate data to study place of death in 9 European countries: opportunities and weaknesses

Background: Systematic and reliable epidemiological information at population level, preferably cross-national, is needed for an adequate planning of (end-of-life) health care policies, e.g. concerning place of death, but is currently lacking. This study illustrates opportunities and weaknesses of death certificate data to provide such information on place of death and associated factors in nine European countries (seven entire countries and five regions).Methods: We investigated the possibility and modality of all partners in this international comparative study (BE, DK, IT, NL, NO, SE, UK) to negotiate a dataset containing all deaths of one year with their national/regional administration of mortality statistics, and analysed the availability of information about place of death as well as a number of clinical, socio-demographic, residential and healthcare system factors.Results: All countries negotiated a dataset, but rules, procedures, and cost price to get the data varied strongly between countries. In total, about 1.1 million deaths were included. For four of the nine countries not all desired categories for place of death were available. Most desired clinical and socio-demographic information was available, be it sometimes via linkages with other population databases. Healthcare system factors could be made available by linking existing healthcare statistics to the residence of the deceased.Conclusion: Death certificate data provide information on place of death and on possibly associated factors and confounders in all studied countries. Hence, death certificate data provide a unique opportunity for cross-national studying and monitoring of place of death. However, modifications of certain aspects of death certificate registration and rules of data-protection are perhaps required to make international monitoring of place of death more feasible and accurate