Explorative Analyse solider, invasiver Sekundärmalignome nach allogener peripherer Blutstammzelltransplantation

Longer survival times have led to a wider importance of long-term consequences after allogeneic stem cell transplantation in the past years. Solid second cancers are one of these. There were found various risk factors after bone marrow transplantation, for instance Graft-verus-Host-Disease and its immunosuppressive therapy, in many published studies before. However there is a loss of information about second cancers particularly after peripheral blood stem cell transplantation. Because this kind of stem cell transplantation is associated with a higher incidence of Graft-versus-Host-Disease it could play an indirect role in the occurence of solid second cancers. In this study all solid, invasive second cancers of patients after peripheral blood stem cell transplantation were detected that occured in the period from 01.01.1999 to 31.12.2013 in the Carreras Leukämie Centrum in Marburg. To generate hypotheses, the influence of selected factors on the occurence of solid second cancers was explored. Finally 398 patients were available for this restrospective investigation. The main statistical method was a univariate Cox-Model in the presence of competing risks. It was used to investigate the impact of selected variables (sex, indication, condtioning regimen, relation between donor and recipient, HLA-compatibility, Graft-versus-Host-Disease etc.) on the development of „solid second cancers“ and „death“ as a competing risk. 16 solid, invasive second cancers with a cumulative incidence of 2 % after 5 and 5.6 % after 10 years after transplantation were detected. The skin was the most represented organ in which second cancers manifestated (Malignant Melanomas: 2x, squamous cell carcinomas: 3x). Squamous cell carcinomas occured most frequently (skin: 3x, tongue: 2x, esophagus: 1x). In each of these cases the patients had a chronic Graft-versus-Host-Disease before the diagnosis of cancer. In the Cox-Model there was no factor with a significant influence on the development of solid second cancers. The competing risk „death“ was significantly associated with the absence of chronic Graft-versus-Host-Disease (Hazard Ratio 2.83, 95% confidence interval 2.15 | 3.71, p-value < 0.001). In this study the small sample of patients, the unicentric design and the small number of solid second cancers represent relevant limitations and are discussed extensively. Although the results were not significant, second cancers were at least associated with chronic Graft-versus-Host-Disease in this cohort. Furthermore squamous cell carcinomas occured in typical organ systems like it was published in representative studies before. These results could be interpreted as an indirect impact of peripheral blood stem cell transplantation on the occurence of certain solid second cancers. The significant association between chronic Graft-versus-Host-Disease and the lower risk of death could be explained by the Graft-versus-Leukemia-Effect. Finally the predicted accumulation of long-term survivors after allogeneic stem cell transplantation will lead to a higher amount of second cancers and priority of oncological follow-up concepts. Because worldwide peripheral stem cells are the leading stem cell source and its use definitely tends to continue, the role of peripheral blood stem cell transplantation in the development of secondary malignancies should be further investigated in large, multicentric studies.