Identification and utilization of donor and recipient genetic variants to predict survival after HCT: are we ready for primetime?

Lara E Sucheston-Campbell,Kenan Onel,Qianqian Zhu,Philip L Mccarthy,Alyssa Clay,Leah Preus,Marcelo Pasquini,Theresa Hahn

doi:10.1007/s11899-014-0246-x

Abstract

Overall survival following hematopoietic cell transplantation (HCT) has improved over the past two decades through better patient selection and advances in HLA typing, supportive care, and infection prophylaxis. Nonetheless, mortality rates are still unsatisfactory and transplant-related mortality remains a major cause of death after unrelated allogeneic HCT. Since there are no known pre-HCT, non-HLA biologic predictors of survival following transplant, for over a decade, scientists have been investigating the role of non-HLA germline genetic variation in survival and treatment-related mortality after HCT. Variation in single nucleotide polymorphisms (SNPs) has the potential to impact chemotherapy, radiation, and immune responses, leading to different post-HCT survival outcomes. In this paper, we address the current knowledge of the contribution of genetic variation to survival following HCT and discuss study design and methodology for investigating HCT survival on a genomic scale.

Highlights

The most successful curative therapy for many malignant hematologic diseases is hematopoietic cell transplantation (HCT). The success of this treatment is limited by transplant-related mortality (TRM)
TRM remains a major cause of death, with disease-related mortality (DRM) the other largest contributor [4]
Variants have been selected in genes relating to immune response to infection and inflammatory reactions, with the goal of understanding the biological basis of TRM

Summary

Introduction

The most successful curative therapy for many malignant hematologic diseases is hematopoietic cell transplantation (HCT). The success of this treatment is limited by transplant-related mortality (TRM). TRM remains a major cause of death, with disease-related mortality (DRM) the other largest contributor [4]. Variation in single nucleotide polymorphisms (SNPs) may lead to differential gene transcription, translation, and protein structure. These changes have the potential to modify immune responses or side effects of chemotherapy and/or radiation, and survival outcomes in HCT patients [5, 6]. Variants have been selected in genes relating to immune response to infection and inflammatory reactions, with the goal of understanding the biological basis of TRM

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Results

Conclusion