Impact of Graft Versus Host Disease on Incidence of Secondary Skin Cancers in Allogeneic Bone Marrow Transplant Recipients

Abstract

Background: Advances in treatment of pediatric acute lymphoblastic leukemia (ALL) have resulted in almost 90% 5-year survival of these children. Still, a small group of ALL-patients experience relapse after initial treatment and, together with those children that are presented with unfavorable biomarkers at diagnosis and those with a high minimal residual disease (MRD) despite treatment, they compose a group that are candidates for hematopoietic stem cell transplantation (HSCT). After HSCT, the leukemic clone is monitored by MRD and chimeric analysis. However, relapse still occurs in 30% of patients after HSCT, hence more prognostic markers are needed in the clinic. TP53 is a tumor suppressor gene encoding protein 53 (p53) which is involved in regulation of the cell cycle. In adults, mutations in TP53 are commonly associated with solid tumors however and they also occur in 10-20% of hematological malignancies, often associated with aggressive disease. Mutations in the tumor suppressor gene TP53 are rare at diagnosis of pediatric ALL but somewhat more frequent at relapse. Intense expression of p53 protein has been associated with underlying mutations in the TP53 gene. Our aim was to evaluate if alterations in the expression of the cell cycle regulating protein p53, analyzed by immunohistochemistry (IHC), could act as a prognostic indicator for relapse in pediatric ALLpatients that undergo HSCT. Procedure: Paraffin embedded bone marrow samples from 49 children diagnosed with ALL between 1997-2010, and treated with HSCT at Karolinska University hospital, were analyzed by tissue micro array and IHC. Samples were analyzed independently at the following times; diagnosis, before HSCT and after HSCT at 0-3, >3-6 and >6-12 months. Samples were analyzed for both total expression and strong expression of p53 protein. Result: Strong expression of p53 in the bone marrow at 0-3months after HSCT was associated with increased risk of relapse, odds ratio 2.63 (confidence interval 1.08-6.40) P = .033. Conclusion: Evaluation of p53 protein expression in bone marrow from pediatric ALL-patients that undergo HSCT, analyzed by IHC which is an available and cost-effective method, may have potential as an additional prognostic marker for predicting relapse after HSCT.