engleski

Long term off-line extracorporeal photochemotherapy for chronic graft-vs-host disease: a 9 year single center experience

Introduction: Extracorporeal photochemotherapy (ECP), as a safe and non-toxic immunotherapeutic method that is able to mediate patient's immune system without generalized immunosuppression, has been used in our center since 2007. After the establishment of multidiciplinary Center for cGVHD and long- term follow-up at University Hospital Center (UHC) Zagreb in 2013. all patients referred to ECP were scored according to established cGVHD related grading scales and measurements in collaboration with the National Cancer Institute, USA, and patients previously treated with ECP were rescored. Material (or patients) and methods: The aim of the study was to report our 9 year experience with clinical and immunomodulatory effect of ECP, as well as adverse reactions associated with ECP.The influence of the EPC treatment on the levels of T-lymphocyte subsets, B lymphocytes, and NK cells in blood was evaluated. Study was performed throughout the period of 2007-2015 in UHC Zagreb on group of 13 patients (7 male, 6 female) who were treated with off-line ECP. MNC were collected with Cobe Spectra and Optia cell separators. After the addition of psoralen products were irradiated with UVA on Macogenic device. Patients' median age was 32 years (range, 12-69 years). The patients suffered from generalized sclerodermatous skin changes, impaired join mobility and joint pain. In 3 patients the symptoms of oral disease have developed. Peripheral blood samples taken before and after leukapheresis, and samples from leukapheresis bag were analyzed for WBC, Htc, MNC, and platelet counts. Number of T-lymphocyte subsets (CD3+, CD3+4+, CD3+8+, CD4+8+ ratio) B- lymphocytes (CD 19+), and NK cells (CD56+) in patient's peripheral blood were taken monthly. Blood counts and parameters of MNC were measured by means of analyzer Advia 120, Bayer, USA. The levels of B, T lymphocytes and NK cells were evaluated by the use of flow cytometry technique, Becton Dickinson, Facs Calibur, USA. Results: In 13 patients with cGVHD, scored according to NIH classification as 11 severe and 2 moderate, 664 ECP procedures were performed. The median number of ECP procedures performed per patient was 49 (range 12-131). Clinical response to ECP is typically delayed until 2 to 3 months. Overall response, defined as either a complete response (CR) or a partial response according to NIH criteria, was obtained in 8 of 13 patients (61, 5%), and CR, in 4 of 13 (30, 7%). The effect of ECP in patients with skin and joint involvement was mostly benefitcal, as well as in all patients who suffered from the oral disease. At last follow up, 10 patients were alive and well and 3 patients died. In patients who responded well to ECP, CD4+/CD8+ ratio and number of NK cells were normalized. In general, ECPs were well tolerated, and main issue was adequate venous access for long term ECP treatment. No increased incidence of infections and no serious adverse reactions have been observed so far. Conclusion: ECP is safe procedure that may be beneficial in treatment of cGVHD and can be recommended for patients who do not respond to conventional therapy. The specific influence of ECP on T-cell subsets leads to the suggestion that interactions between T-cell subsets may participate in the process of ECP.

chronic graft versus host disease; extracorporeal photochemotherapy

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