Title Dijagnostika i terapija posttransplantacijskih limfoproliferativnih bolesti Title (english) Diagnosis and therapy of posttransplant lymphoproliferative disorders Author Tihana Duić Mentor Slobodanka Ostojić-Kolonić (mentor)Committee member Tomislav Letilović (predsjednik povjerenstva)Committee member Jasenka Markeljević (član povjerenstva)Committee member Slobodanka Ostojić-Kolonić (član povjerenstva)Granter University of Zagreb Defense date and country 2020-07-17, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Postransplantacijske limfoproliferativne bolesti su heterogena skupina limfoma koja predstavlja ozbiljnu komplikaciju transplantacije solidnih organa i hematopoetskih matičnih stanica povezanu s lošim ishodom i visokim mortalitetom. Iako su se PTLB nekada smatrale izuzetno rijetkima, podatci prikupljeni u prošlom desetljeću pokazuju kako se ipak radi o komplikaciji koja nije neuobičajena. Limfomi čine čak 21% svih malignosti među pacijentima kojima je transplantiran solidni organ, u usporedbi s 4% malignosti u ženskoj i 5% malignosti u muškoj imunokompetentnoj populaciji. Osnovna pretpostavka za razvoj PTLB jest terapijska imunosupresija koju primaju transplantirani pacijenti. U uvjetima takve imunosupresije, adekvatan imunološki odgovor organizma je suprimiran. U patofiziološkom smislu velik broj PTLB je posljedica nekontrolirane primoinfekcije ili reaktivacije Epstein-Barr virus infekcije koja u uvjetima suprimiranog odgovora citotoksičnih T- lmfocita dovede do maligne alteracije B-limfocita i nastanka limfoma. Drugi dio PTLB, čiji nastanak nije povezan s EBV infekcijom, već nastaju „de novo“, također se smatra posljedicom narušenog imunosnog sustava. PTLB limfomi razlikuju se od limfoma kod imunokompetentnih osoba po svojim karakteristikama (specifičnoj patofiziologiji i predilekcijskim mjestima) i zahtijevaju drugačiji pristup dijagnostici i liječenju. Zlatni standard u dijagnostici PTLB jest patohistološka dijagnostika i kategorizacija prema Klasifikaciji Svjetske zdravstvene organizacije iz 2017. Za utvrđivanje proširenosti bolesti koriste se radiološke metode, ponajprije CT. PET-CT se pokazao kao iznimno specifična i osjetljiva metoda za procjenu proširenosti i odgovora na terapiju PTLB, ali preporuke za njegovo korištenje još nisu jednoznačne i potrebna je dodatna potvrda za korištenje ove metode. Veliki je udio PTLB povezan s EBV infekcijom i to daje mogućnost probira pacijenata na PTLB na temelju razine EBV u krvi i adekvatne profilaktične ili preemptivne intervencije. Iako još ne postoje standardizirani protokoli, probir se uglavnom temelji na identifikaciji visokorizičnih pacijenata i praćenju razine EBV u krvi pacijenta. Terapijske strategije za liječenje PTLB uključuju redukciju imunosupresije, kirurgiju, radioterapiju, adoptivnu imunoterapiju (EBV specifični CTL), kemoterapiju, rituksimab i transplantaciju hematopoetskih matičnih stanica. Terapije su prilagođene tipu limfoma. Potraga za optimalnom terapijom koja bi objedinila maksimalni terapijski učinak s minimalnim toksičnim učinkom još traje.
Abstract (english) Posttransplantation lymphoproliferative disorders are heterogeneous group of lymphomas. They develop as a serious complication of solid organ and haematopoietic stem cells transplantation and are associated with poor outcomes and high mortality. Even though PTLDs were considered to be a very rare complication, data from the last decade suggests that they are as not uncommon as they were previously thought to have been. When put in perspective, lymphoma make 21% of all cancers in population of solid organ transplant patients, whereas in immunocompetent patients they make for only 4% of cancers in women and 5% of cancers in men. Transplanted patients are given high doses of immunosuppression and that is the main reason for PTLD development. In conditions of immunosuppression patient’s immune system is impaired. In terms of pathogenesis, large number of PTLDs are driven by uncontrolled EBV infection, primary or reactivation, which is a consequence of inadequate immune response (no EBV specific CTLs) due to immunosuppression and which leads to malignant alteration of infected B lymphocytes. PTLDs whose development is not generated by EBV infection, but rather appear as “de novo” malignancies, are also associated with immunosuppression. PTLDs differ from lymphomas in immunocompetent patients. They have specific pathogeneses as well as predilection spots (mostly extra nodal) and they also require specific diagnostic and therapeutic approaches. The golden standard for the diagnosis of PTLD is histopathological examination and categorization based on the World Health Organization 2017 classification. Radiologic methods, mostly CT, are used to establish the stage of the lymphoma. PET-CT has proven to be highly sensitive and specific method for staging of the PTLD, but its use for staging and the assessment of the response to treatment still needs validation. Given the fact that a great deal of PTLDs are EBV driven, measurement of EBV viral loads can be used for screening of the PTLD patients for adequate prophylaxis and preemptive interventions. There are no standardized protocols for screening of the patients, but it is mostly based on identification of high risk patients and measurement of EBV viral loads. Therapeutic strategies for PTLDs include reduction of immunosuppression, surgery, radiotherapy, adoptive immunotherapy, chemotherapy, rituximab, and haematopoietic stem cell transplantation. Therapies are lymphoma specific. Search for optimal therapy that has maximal therapeutic and minimal toxic effect is still on-going.
Keywords
posttransplatacijske limfoproliferativne bolesti
transplantacija
imunosupresija
EBV infekcija
dijagnostika
terapija
Keywords (english)
posttransplant lymphoproliferative disorders
transplantation
immunosuppression
EBV infection
diagnosis
therapy
Language croatian URN:NBN urn:nbn:hr:105:560863 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2021-09-06 08:53:22
