EKSTRAKORPORALNA FOTOFEREZA U LIJEČENJU KRONIČNE REAKCIJE TRANSPLANTATA PROTIV PRIMATELJA

Ines Bojanić, Ranka Serventi Seiwerth, Sanja Mazić, Klara Dubravčić, Drago Batinić, Branka Golubić Ćepulić, Boris Labar

Ekstrakorporalna fotofereza (EF) jest imunomodulatorna terapija koja se rabi u liječenju kronične reakcije transplantata protiv primatelja (engl. chronic graft versus host disease, cGVHD). Tijekom EF-a leukaferezom se iz krvi izdvajaju mononuklearne stanice, ex vivo im se dodaje 8-metoksipsoralen, stanice se ozrače UVA-zrakama i potom reinfundiraju bolesniku. Cilj istraživanja bio je procijeniti klinički i imunomodulatorni učinak postupka EF-a u bolesnika s cGVHD-om. Analiziran je 341 postupak EF-a u 7 bolesnika s cGVHD-om s medijanom EF-a po bolesniku 37 (raspon 13–131). U svih bolesnika cGVHD se manifestirao kožnim promjenama u kombinaciji sa simptomima drugih organskih sustava. EF su provođene dva dana za redom: prvih mjesec dana svaki tjedan, sljedeća 2 mjeseca svaki drugi tjedan, a potom jednom na mjesec. Medijan trajanja liječenja postupkom EF-a iznosio je 10 mjeseci (raspon 2 do 58). EF je većinom povoljno utjecao na simptome cGVHD-a pa je u 6 bolesnika došlo do poboljšanja i/ili stabilizacije promjena kože te bolje pokretljivosti zglobova, a u 2 bolesnika s ulceracijama sluznice usne šupljine promjene su se u cijelosti povukle. Do kliničkog poboljšanja došlo je 2 do 3 mjeseca nakon početka EF-a, što je omogućilo značajno smanjenje ili prestanak primjene glukokortikoida. Neželjene reakcije javile su se tijekom 4,9% postupaka. U bolesnika u kojih je došlo do poboljšanja kliničkog stanja normalizirale su se vrijednosti omjera CD4+/CD8+ stanica, kao i broj NK-stanica. Rezultati našeg istraživanja pokazuju da primjena EF-a povoljno utječe na simptome cGVHD-a i omogućuje sniženje doze kortikosteroida uz poboljšanje kvalitete života bolesnika pa se stoga može preporučiti za bolesnike koji ne odgovaraju na standardno liječenje.

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy which has been used in the treatment of chronic GVHD (cGVHD). ECP involves separation of the mononuclear cells with leukapheresis, followed by ex vivo administration of 8-methoxypsoralen and UV-A radiation and reinfusion to the patient. Aim of the study was to evaluate clinical and immunomodulatory effect of ECP procedures in patients with cGVHD. We analyzed 341 ECP procedures performed in 7 patients with cGVHD; median ECP per patient was 37 (range 13–131). All patients suffered from skin changes in combination with impaired joint mobility and symptoms of oral disease. ECP procedures were performed for two consecutive days: in initial phase weekly, followed by every two weeks and than monthly according to clinical response. Median of ECP treatment duration was 10 months (range 2–58). The effect of ECP in patients with cGVHD with skin and joint involvement was mostly beneficial: 6 patients experienced either improvement or stabilization in skin changes and joint mobility. In 2 patients who suffered from oral disease, the total recovery was observed. Clinical response was typically delayed until 2 to 3 months, and reduction in glucocorticoid dose was observed. Adverse reactions were observed in 4.9% procedures. In patients who responded to ECP treatment, CD4+/CD8+ ratio and number of NK cells were normalized. ECP proved to be an efficient and safe procedure that may be recommended for patients with cGVHD who do not respond to conventional therapy.