Alogenična transplantacija od HLA haploidentičnog obiteljskog darivatelja

master's thesis

• Title (english): Allogeneic transplantation from a HLA haploidentical family donor
• Author: Dora Raos
• Mentor: Nadira Duraković (mentor)
• Committee member: Zinaida Perić (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Nadira Duraković (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2021-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Alogenična transplantacija krvotvornih matičnih stanica danas je važan terapijski zahvat u liječenju mnogih malignih i nemalignih hematoloških, ali i nehematoloških bolesti. Glavni cilj takvog liječenja je zamijeniti bolesnu ili nefunkcionalnu koštanu srž primatelja zdravim krvotvornim matičnim stanicama darivatelja. Osim što je za uspješno provođenje transplantacije važan preduvjet podudarnost u sustavu antigena tkivne podudarnosti (HLA sustav), također je bitno provesti ispravan režim kondicioniranja u sklopu predtransplantacijske pripreme pacijenta. Dvije su glavne vrste TKMS – autologna (gdje su darivatelj i primatelj ista osoba) i alogenična (gdje su darivatelj i primatelj različite osobe). Dok je u prošlosti glavni izvor KMS bila koštana srž, danas se sve češće KMS uzimaju iz periferne krvi što je puno sigurniji i bezbolniji pristup za darivatelja. Darivatelj za alogeničnu transplantaciju može biti srodan ili nesrodan, HLA – podudaran ili HLA – nepodudaran. Najbolji ishodi transplantacije postižu se od HLA – podudarnog srodnog darivatelja, no takvog darivatelja ima vrlo mali broj pacijenata, stoga se razvila potreba za otvaranjem Registara dobrovoljnih (nesrodnih) darivatelja krvotvornih matičnih stanica diljem svijeta te za razvojem protokola koji će omogućiti povoljne ishode transplantacije uz korištenje presadaka od HLA – nepodudarnih darivatelja. Danas postoje tri protokola koja nam omogućuju zaobilaženje povijesnih barijera haploidentične transplantacije krvotvornih matičnih stanica, svaki od njih sa svojim prednostima i nedostatcima – deplecija limfocita T s unošenjem „megadoze“ CD34 stanica (TCD protokol), alografti pripremljeni s faktorom rasta granulocita u kombinaciji s intenzivnom farmakološkom imunosupresijom (GIAC protokol) i posttransplantacijska uporaba visokih doza ciklofosfamida (PTCy protokol).

Abstract (english)

Allogeneic haematopoietic stem cell transplantation is today an important therapeutic procedure in the treatment of many malignant and non – malignant haematological and non – haematological diseases. The main purpose of such treatment is to replace the recipient’s ill or dysfunctional bone marrow with healthy donor's haematopoietic stem cells. In addition to being an important prerequisite for successful transplantation, matching in the human leukocyte antigen system (HLA system), it is also important to implement the correct conditioning regimen as part of the patient's pre – transplant preparation. There are two main types of haematopoietic stem cell transplantation – autologous (where the donor and the recipient are the same person) and allogeneic (where the donor and the recipient are different people). While in the past the main source of haematopoietic stem cells was bone marrow, today more and more haematopoietic stem cells are taken from peripheral blood which is a much safer and painless approach for the donor. The donor for allogeneic transplantation can be related or unrelated, HLA – matched or HLA – mismatched. The best outcomes of transplantation are achieved from HLA – matching related donor, but very small number of patients has such a donor, so the need to open Registers of voluntary (unrelated) haematopoietic stem cell donors has developed worldwide and to develop protocols that will enable favorable transplant outcomes using transplants from HLA – mismatched donors. Today, there are three protocols that allow us to circumvent the historical barriers of haploidentical haematopoietic stem cell transplantation, each with its advantages and disadvantages – T – cell depletion with „megadose“ CD34+ cells (TCD protocol), granulocyte colony – stimulating factor – primed allografts combined with intensive pharmacological immunosuppression (GIAC protocol) and high – dose, post – transplantation cyclophosphamide (PTCy protocol).

• Keywords: transplantacija krvotvornih matičnih stanica; sustav antigena tkivne podudarnosti; liječenje; darivatelj
• Keywords (english): haematopoietic stem cell transplantation; human leukocyte antigen system; treatment; donor
• Language: croatian
• URN:NBN: urn:nbn:hr:105:525377
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-05-04 11:51:59