Özet:

Aim: This prospective study aimed to observe the changes in oxidative stress indicators, including total anti-oxidant status (TAS), total oxidant status (TOS), paraoxanase-1 (PON1), total thiol (TT), native thiol (NT), disulphide (DS) and nitric oxide (NO) levels from sequential blood samples obtained during a de-novo episode of acute graft versus host disease (aGvHD) and evaluate their association with disease severity and the risk of steroid resistant disease. Material and Method: Sequential patients who underwent an allogeneic stem cell transplantation (ASCT) in our unit and subsequently developed a de-novo episode of aGvHD between January 2022 and May 2022 were included in case they gave informed consent. All patients were started high dose (2 mg/kg/day) methylprednisolone as institutional standard first-line treatment of aGvHD as soon as the clinical diagnosis is evident. All episodes were confirmed simultaneously with gastrointestinal (GI) endoscopy and/or skin biopsies. TAS, TOS, PON1, TT, NT, DS and NO were studied from blood samples collected on days 0, +3 and +7 of steroid treatment. Demographic characteristics, diagnoses, donor type, GvHD prophylaxis, stage and grade of aGvHD, performance status (PS), the presence of cytomegalovirus (CMV) reactivation and response to steroid therapy were also noted. Results: A total of 15 cases was included. The median age was 49 (23-77). Males constituted 60.0% (n=9). The most frequent diagnosis and donor type were acute leukemia (53.3%, n=8) and matched related donor (46.7%, n=7), respectively. High grade aGvHD with Glucksberg grading and International Bone Marrow Transplant Registry severity index (IBMTR-SI) included 53,3% (n=8) and 86.7% (n=10) of cases, respectively. Non-responders (20.0%, n=3) significantly had advanced stage GI involvement, higher grade of aGvHD with Glucksberg grading and IBMTR-SI, and lower PS (p=0.005, p=0.04, p=0.006, and p=0.02, respectively). The changes in TAS, TOS, PON1, TT, NT, DS and NO levels on days 0, +3 and +7 of steroid treatment were not significant. Median PON1 levels on days 0, +3 and +7 of steroid treatment were significantly lower among non-responders (p<0.01, p<0.02, and p=0.03, respectively). Conclusion: Steroid resistant aGvHD is an important cause of morbidity and mortality after ASCT. Advanced stage GI involvement and higher total grade of aGvHD is associated with steroid resistance. Lower PON1 levels may be employed as an early indicator of steroid resistance and thus may allow for the early start of more aggressive therapies. Cut-off values and possible confounders should be investigated in further studies.

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