Late effects and health-related outcomes after allogeneic hematopoietic stem cell transplantation in childhood

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment for many acquired or congenital disorders of the hematopoietic system. For some patients it may be the only curative option. Most children become long-term survivors and late toxicities are a major concern as their impact on health and quality of life can be serious. Therefore, a better understanding of the patterns of long-term toxicities and their risk factors is needed for more tailored treatment planning, follow-up programs and patient counseling. The general aim of the thesis was to study the spectrum of late toxicities in long-term survivors of pediatric allo-HSCT, to identify risk factors for adverse events and assess the additive toxicity associated with allo-HSCT in the treatment of childhood acute myeloid leukemia (AML). In a retrospective case-note review, data was extracted from medical records of 204 allo-HSCT survivors with ≥4 years’ follow-up after allo-HSCT. Special focus was placed on gonadal function and pubertal development in 96 female allo-HSCT survivors (Paper I) and in 102 male survivors (Paper II). The burden of late adverse events was analyzed for the whole cohort of long-term survivors (Paper III) and the impact of various conditioning regimens based on cyclophosphamide (Cy), busulphan (Bu), single fraction or fractionated total body irradiation (sTBI or fTBI) was evaluated. In order to assess the additive late toxicity associated with allo-HSCT in the treatment of childhood AML, questionnaire data derived from 95 Nordic childhood AML survivors treated with allo-HSCT was compared with corresponding data collected previously from 101 childhood AML survivors treated according to the common Nordic AML treatment protocols but without allo-HSCT; siblings of allo-HSCT survivors were used as a second control group (n=53) (Paper IV). The burden of endocrine late effects was high after pediatric allo-HSCT; 38% had been treated with growth hormone, 38% had thyroxine substituted hypothyroidism, 50% had been treated with sex steroids, and 84% had at least one non-endocrine chronic health condition. TBI-based conditioning regimens were associated with the highest numbers of endocrine disorders, whereas the main risk factor for non-endocrine chronic conditions was chronic Graft-versus-Host Disease (Paper III). The risk of ovarian failure was high after both TBI- and Bu-based conditioning regimens and more than half (66%) of the female survivors needed hormone replacement therapy at their latest visit (Paper I). For male survivors, the recovery of spermatogenesis after allo-HSCT appeared more likely after chemotherapy-based conditioning regimens. Larger adult testicular volumes correlated with an active spermatogenesis suggesting that adult testicular volumes above 15mL may predict recovering spermatogenesis after allo-HSCT (Paper II). In the treatment of childhood AML, allo-HSCT was associated with significantly higher numbers of self-reported chronic conditions and health limitations, supporting the restriction of allo-HSCT to selected high-risk patients in first complete remission, whereas allo-HSCT without TBI after relapse may increase the risk of cardiovascular disorders (Paper IV). Several natural pregnancies were reported after allo-HSCT in childhood or adolescence (Papers III and IV). Our findings contribute to the expanding pool of knowledge on late complications after pediatric allo-HSCT

Hospitalizations in long-term survivors of childhood AML treated with allogeneic HCT-An Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study

Non peer reviewe

Wear protection of deep drawing tools by systematic optimization of highly stressed surfaces

The automotive sector is one of the largest energy consumers in Germany. Requests from politics and industry to significantly reduce emissions require new developments during utilization as well as during production phase. In line with the framework concept "InnoCaT", where more than 60 companies and research facilities from Germany take part, possibilities for producing companies are developed and analyzed to reduce the resource and energy consumption and by this reducing costs along the entire process chain of car body manufacturing. One approach to design car bodies lighter and more efficiently is to use aluminium and high strength steels. By this means weight and sheet thickness are reduced. However higher strengths of the steels and the adhesion affinity of aluminium significantly increase the requirements regarding the used tool steel. Thus grooves or galling appear more frequent at highly stressed surfaces. To assure high lifetimes and by this increase especially the resource efficiency concerning use of material and setting-up times within the press plant, a local optimization at the highly stressed surfaces is necessary. For this a FEM/BEM-tool for a time efficient and exact calculation of the occurring tool loads for complex die profiles is developed. Based on this development of load calculation a shape-optimization is performed at the corresponding areas. After the geometric optimization of the tool a local laser surface treatment for further wear protection is carried out using laser cladding or laser alloying/ -dispersing. By combining the technologies a highly wear resistant surface is achievable, which increases the tool's lifetime as well as the reproducibility within production