Clinical aspects of chronic graft-versus-host disease

Detta är en avhandling från Stockholm : Karolinska Institutet, Dept of Medicine, Huddinge

Sammanfattning: Chronic graft-versus-host disease (cGVHD) remains one of the most severe complications after allogeneic hematopoietic stem cell transplantation (HSCT), affecting both the quality of life and mortality of long-term survivors. Its impact on morbidity and mortality varies depending on the severity and number of organs involved, allowing classification into mild, moderate, and severe cGVHD according to the National Institute of Health criteria (NIH). Chronic GVHD is associated with a graft-versus-tumor effect (GVT) that decreases the risk of relapse after transplantation. Treatments involve potent immunosuppressive modalities with side effects including infections and possibly relapse of the underlying malignancy. The aim of this thesis is to increase the knowledge of cGVHD with emphasis on early detection of risk and prognostic factors in order to allow a more vigilant management of the syndrome as well as the evaluation of extracorporeal photopheresis. In paper I we performed a retrospective study with emphasis on risk factors for the development of cGVHD. We showed a significantly higher incidence of severe cGVHD in patients with sibling donors compared to unrelated donors (URD). Relapse and Transplant-related-mortality (TRM) were similar in both groups. However, TRM was significantly higher in patients with severe cGVHD. The main findings were that despite HSCTs with sibling donors showing higher incidence of cGVHD they resulted in significantly better 5-year overall survival (OS) and relapse-free survival (RFS) compared to patients with a URD. Paper II is a multi-centre retrospective analysis with the aim to determine early detectable risk factors for the development of cGVHD. We found that risk factors for severe cGVHD include female donor to male recipient, reduced intensity conditioning and older patient age. In 2005 the NIH formed consensus criteria for the diagnosis of cGVHD. The new scoring system proved time-consuming and difficult to manage during a standard out-patient visit. In paper III we aimed to determine the prognostic impact of the new NIH score and also of the newly implemented sub-categories of cGVHD, namely overlap syndrome and delayed acute GVHD. Our aim was to develop a simplified score with similar prognostic impact as that of the NIH score. We could show that factors adversely affecting prognosis upon diagnosis of cGVHD include ECOG, platelet count and, if present, severe gut involvement. In fact, by only using the combination of ECOG and platelet count we could identify the same prognostic risk groups. The most well-established second line treatment for steroid-refractory, - intolerant or –dependent cGVHD to date is extracorporeal photopheresis (ECP). In paper IV we could conclude that ECP was a safe and well-tolerated treatment. Patients with severe skin cGVHD had the best response in terms of complete or partial response. To summarize, this thesis provides new data regarding risk and prognostic factors for cGVHD which has led to perhaps a more-user friendly prognostic tool upon diagnosis of cGVHD. The findings help us to decide on immunosuppression for URD and what patient group would benefit the most from ECP treatment.

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