ABSTRACT
Background: allogeneic hematopoietic stem cell transplantation [HSCT] is widely used to treat various hematological malignant and non-malignant diseases. The occurrence of complications following HSCTas graft versus host disease[GVHD], hepatic veno-occlusive disease [VOD], oral mucositis [OM], drug induced hepatic and renal adverse events- is highly variable and dependent on a multitude of host, donor, and treatment factors. Identifying important genetic variables will allow for better prediction of HSCTrelated outcomes, and in the process of identifiing these susceptibilities, that could help to develop targeted interventions
Objectives: to evaluate impact of the C677T polymorphism of 5,10-methylenetetrahydrofolate reductase [MTNFR] on the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation as acute gruff versus host disease [GVHD],oral mucositis ,drug induced hepatic and renal toxicity, transplant related mortality[TRM] and overall survival[OS]
Patients and Methods: we examined the association of a single nucleotide polymorphism [SNP] at position 677 in the MTHFR gene of patients with outcomes of allogeneic HSCT. MTHFR genotyping was performed by po2ymerase chain reaction-restriction fiagment length polymorphism [PCR-RFLP]
Results: 46 Patients with complete clinical records were recruited. Median age at the time of HSCT was 22 years [range 3-42 years]; 32 patients [69.6%] above >/=18 years, and the median follow-up period of survivors was 21 months. 212efrequencies of the MTHFR C677T genotypes in patients were 43.5% [20 patients] for 677CC, 50% [23 patients] for 677CX and 6.5% [3 patients] for 677TT; the allelic frequency of the 677T was 31.5%. Recipient MTHFR677 in CT or TT versus CC showed non-statistically significant higher incidence of acute GVHD [7/26] 26.9% versus [2/20] 10%; p=0.15, hepatic toxicity [11/26] 42.3% versus [5/20] 25%, p= 0.22 and TRM [5/26] 19.2% versus [2/20] 10%; p=0.45. Recipients with variant allele MTHFR 677T were associated with lower non statistically signijicant overall survival; p=0.281. Conclusion: Genofyping for WHFR C677T before HSCT could have clinical significance, not statistically proven in our study, in prediction of patients at high risk of developing poor outcomes. Larger studies with homogeneous HSCT cohort are needed to identifi such potential phar]nacogenetic markers with suflciently strong evidence to be used in clinical practice