Utjecaj podudarnosti u sustavu HLA na ishod transplantacije krvotvornih matičnih stanica

master's thesis

• Title (english): The impact of HLA matching on the outcome of hematopoietic stem cell transplantation
• Author: Marina Hukelj
• Mentor: Zorana Grubić (mentor)
• Committee member: Zorana Grubić (predsjednik povjerenstva)
• Committee member: Duje Lisičić (član povjerenstva)
• Committee member: Perica Mustafić (član povjerenstva)
• Committee member: Marija Gligora Udovič (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-09-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Transplantacija krvotvornih matičnih stanica (TKMS) koristi se u terapiji raznih malignih i
nemalignih oboljenja. Glavni ograničavajući čimbenik u ishodu alogenične TKMS su geni
glavnog sustava tkivne podudarnost (engl. Human Leukocyte Antigens, HLA). TKMS od
nesrodnog davatelja povećava rizik reakcije transplantata protiv primatelja (engl. Graft
versus Host Disease, GvHD), odbacivanja transplantata te smanjuje preživljavanje. Cilj rada
bio je odrediti razinu i smjer nepodudarnosti HLA na... More lokusima HLA-A, -B,-C, -DRB1, -
DQB1 i -DPB1 u skupini bolesnika (N=54) koji su liječeni alogeničnom TKMS od 9/10
HLA podudarnog nesrodnog davatelja, utvrditi utjecaj HLA i ne-HLA čimbenika na ishod
TKMS, odnosno, na pojavu GvHD-a, povrata bolesti te na preživljenje bolesnika. Svi
ispitanici testirani su za lokuse HLA jednom od molekularnih metoda temeljenih na lančanoj
reakciji polimerazom. Većina nepodudarnosti na lokusu HLA-A bila je na razini gena
(85,00%), dok su nepodudarnost na lokusu HLA-DRB1 najčešće bile na razini alela
(76,92%). Nepodudarnost na lokusu HLA-DPB1 (87,04%) bila je u skladu s literaturom.
Bolesnici s dva nepodudarna alela HLA-DPB1 imali su češću pojavu GvHD-a nego
bolesnici s jednom ili nijednom nepodudarnošću (P=0,0280). Kod bolesnika kojima je izvor
krvotvornih matičnih stanica bila periferna krv, pojava GvHD-a bila je veća nego kod
bolesnika kojima je izvor bila koštana srž (P=0,0190). Less

Abstract (english)

Hematopoietic stem cell transplantation (HSCT) is used for treatment of various malignant
and non-malignant diseases. Allogeneic HSCT outcome is highly influenced by genes
pertaining to Human Leukocyte Antigens (HLA) complex. HSCT from unrelated donor
increases risk of Graft versus Host Disease (GvHD), transplant rejection and reduces
survival rate. Aims of the study were: to determine level and direction of HLA mismatch at
HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci among patients (N=54)... More who were treated
with HSCT from 9/10 HLA-matched unrelated donor; and to determine influence of HLA
and non-HLA factors on HSCT outcome by investigating their association with GvHD
occurrence, disease relapse and overall survival. All individuals were analyzed for HLA loci
by one of molecular methods based on polymerase chain reaction technology. Majority of
detected HLA-A mismatches were at gene level (85.00%), while HLA-DRB1 mismatches
were found mostly at allelic level (76.92%). HLA-DPB1 mismatch frequency (87.04%)
correlated well with literature data. GvHD occurrence was higher among patients with
mismatch for both HLA-DPB1 alleles in comparison to patients who had one or no mismatch
(P=0.0280). GvHD occurred more frequently among patients transplanted with HSC from
peripheral blood as opposed to those with bone marrow as HSC source (P=0.0190). Less

• Keywords: alogenična transplantacija krvotvornih matičnih stanica; GvHD; HLA-DPB1
• Keywords (english): allogeneic hematopoietic stem cell transplantation (allo-HSCT); GvHD; HLADPB1
• Language: croatian
• URN:NBN: urn:nbn:hr:217:014516
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-09-26
• Created on: 2022-10-21 10:03:11