Title Akutna bolest darivatelja protiv primatelja Title (english) Acute graft versus host disease Author Marija Tominac Mentor Nadira Duraković (mentor)Committee member Radovan Vrhovac (predsjednik povjerenstva)Committee member Jasenka Markeljević (član povjerenstva)Committee member Nadira Duraković (član povjerenstva)Granter University of Zagreb Defense date and country 2022-09-02, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Akutna bolest darivatelja protiv primatelja (aGvHD) najčešća je po život opasna komplikacija alogene transplantacije hematopoetskih matičnih stanica. Predstavlja imunološku reakciju imunokompetentnih T stanica darivatelja koje stanice primatelja prepoznaje kao strane. Mehanizam nastanka ima tri faze. Primjenom zračenja i intenzivne kemoterapije zbog pripreme bolesnika za transplantaciju, dolazi do ozljede tkiva bolesnika te izlučivanja upalnih citokina (I. faza). Ti upalni citokini i antigen-predočne stanice aktiviraju darivateljeve T limfocite koji posreduju aGvHD (II. faza) a koji dodatno izlučivanjem citokina i uz pomoć endotoksina stimuliraju makrofage. Aktivirani makrofazi sa staničnim upalnim efektorskim stanicama dovode do lokalne ozljede tkiva (III. faza). Klasično se pojavljuje unutar sto dana od transplantacije. Može zahvatiti jedan ili više organa: kožu, jetru i gastrointestinalni trakt. Tipične promjene na koži su makulopapulozni osip, generalizirani eritem, a u najtežim slučajevima moguća je epidermioliza s bulama i deskvamacijom. Promjene na jetri očituju se kao hiperbilirubinemija sa žuticom te porastom alkalne fosfataze i serumskog kolesterola, dok se promjene na gastrointestinalnom traktu očituju kao mučnina, proljev i bolovi u trbuhu. Dijagnoza se postavlja na osnovi kliničke slike i histološkog nalaza biopsije kože, crijeva ili rjeđe jetre. U profilaksi pojave akutnog GVHD primjenjuje se najčešće inhibitor kalcineurinskih receptora (ciklosporin ili takrolimus), sam ili u kombinaciji s nekim drugim imunosupresivnim lijekom (načešće metotreksat u bolesnika nakon mijeoablativne pripreme, te mikofenolat-mofetil u bolesnika nakon nemijeloablative pripreme. Terapija ovisi o simptomima, zahvaćenosti organa i profilaksi – prvi stadij ne zahtijeva sistemsko liječenje, dok prvi izbor terapije za ostale stadije su sistemski kortikosteroidi. Pri neuspjehu liječenja prvim izborom, druga linija terapije je ruksolitinib, novi lijek s velikom učinkovitosti u liječenju akutnog GvHD-a. Ostali izbor lijekova i terapijskih postupaka u liječenju su antitimocitni globulin, mikofenolat mofetil, monoklonska protutijela, pentostatin, sirolimus, mezenhimalne matične stanice i ekstrakorporalna fotofereza.
Abstract (english) Acute graft-versus-host disease (aGVHD) is the most common life-threatening complication of allogeneic hematopoietic stem cell transplantation. It represents the immune reaction of immunocompetent T cells of a mismatched donor to recipient cells which it recognizes as foreign. The mechanism of occurrence takes place in three phases. The use of radiation and intensive chemotherapy to prepare patients for transplantation results in injuries to the patient's tissues due to the secretion of inflammatory cytokines (phase I). These inflammatory cytokines and antigen-presenting cells activate aGvHD by T donor lymphocytes (phase II) and stimulate macrophages by cytokine secretion and endotoxins. Macrophages with cellular inflammatory effectors secrete cytokines and lead to local tissue injury (phase III). It classically appears within hundred days after transplantation. It can affect one or more organs: skin, liver, and gastrointestinal tract. Typical skin changes are maculopapular rash, generalized erythema and in the most severe cases, epidermolysis with bumps and desquamation as possible. Changes in the liver manifest as hyperbilirubinemia with jaundice and an increase of alkaline phosphatase and serum cholesterol, while changes in the gastrointestinal tract manifest as nausea, diarrhea, and abdominal pain. The diagnosis is based on the clinical signs and histological findings of a biopsy of the skin, rectum and rarely liver. In prophylactic therapy calcineurin inhibitors are most usually used (cyclosporine or tacrolimus), alone or in combination with other immunosuppressive drugs (most usually methotrexate in patients after myeloablative preparation) and mycophenolate mofetil in patients after nonmyeloablative preparation.
Therapy depends on symptoms, organ involvement and prophylaxis – the first stage does not require systemic treatment, while the first choice of therapy for other stages are systemic corticosteroids. If the first-line treatment fails, the second-line therapy is ruxolitinib, a new drug with high efficacy in the treatment of acute GvHD. Other choice of drugs and therapeutic procedures in treatment are antithymocyte globulin, mycophenolate mofetil, monoclonal antibodies, pentostatin, sirolimus, mesenchymal stem cells and extracorporeal photopheresis.
Keywords
aGvHD
klinička slika
profilaksa
terapija
Keywords (english)
aGvHD
clinical manifestation
prophylaxis
therapy
Language croatian URN:NBN urn:nbn:hr:105:217691 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2023-03-20 09:14:38
