Association of hemochromatosis gene mutation frequency with sinusoidal obstruction syndrome and 100 day mortality in hemotopoietic stem cell transplanted patients

Sinusoidal obstruction Syndrome (SOS) is a serious hepatic complication of hematopoietic stem cell transplantation (HSCT) with uncretain etiology. Increased iron stores, have recently been reported to be among the various risk factors predisposing HSCT recipients to SOS. Benign and malignant hematological disease, particularly the ones associated with ineffective hematopoesis and increased transfusion requirements have increased body iron stores and elevated serum ferritin levels. Liver as the major site of iron depositon is particularly susceptible to oxidative stress produced by increased body iron stores. HFE mutations which is the most common genetic disorder of the Northern hemisphere, is also associated with increased body iron stores. We investigated the prevelance of HFE genotypes in various hematological malignancies reqiring HSCT. We also analysed whether the presence of HFE mutations further increases the iron overload in HSCT recipients and predsiposes them to SOS. Day +100 mortality and its relationship with the HFE genotype was also assesed. HFE H63D and C282Y genotypes were determined in 93 HSCT recipents who were evaluated prospectively for the development of SOS. The influence of the HFE genotype on serum iron parameters was also tested.No C282Y mutation was detected while H63D allele frequency was %24,8. Our data suggests that HFE H63D mutation frequency was increased in our patient cohort with various hematological malignancies compared to the general Turkish population (%13,6±5,6). While we could not demonstarte any effect of HFE genotypes on neither the iron status nor on 100 day mortality. Twenty patients had developed SOS all of whom had undergone allogenic HSCT. Allogenic HSCT was found to be a risk factor for SOS (p=0,001). Elevated pretransplant ferritin levels and TBI was independent risk factors for SOS (OR=1,0001 and 6,93, respectively). Serum ferritin was also found to be inversely corralated with day 100 mortality (p=0,003).In conclusion, pretransplantation iron overload seems to play an important role in transplantation outcome. The presence of hetrozigot H63D mutation does not seem to contribute to increased iron overload in HSCT recipients while the role of homozigot mutation remains to be verified. Determination of iron stores might facilitate risk-stratificaiton and developing strategies such as phlebotomy and/or iron chelation to prevent SOS.