In Study, SMRT Sequencing Provides Higher-Resolution HLA Typing Associated with Improved Patient Survival Rates

In a study just published in the Journal of Biology of Blood and Marrow Transplantation, scientists at the Anthony Nolan Research Institute demonstrated that ultra-high-resolution HLA typing performed with SMRT Sequencing identified stronger matches associated with improved survival rates among patients who received hematopoietic cell transplants.
The Anthony Nolan Research Institute, which is funded by Anthony Nolan, a registered UK charity that maintains the world’s oldest stem cell registry, implemented SMRT Sequencing to fully phase and characterize HLA genes with high accuracy. The HLA genes are highly polymorphic and complex, making them very difficult to resolve fully with conventional technologies. A thorough analysis of them is important for finding the best donor/recipient matches for stem cell transplants and other applications.
In this retrospective study, scientists aimed to determine whether high-resolution HLA typing enabled by SMRT Sequencing would have made a difference for previously matched donors and recipients. They analyzed 891 donor/recipient pairs, all of which had originally been considered a perfect match (a 12/12 score for all six HLA genes). SMRT Sequencing revealed that 29.1% of those matches were not actually perfect and identified previously undetected variation in nearly a quarter of the pairs.
The patients whose 12/12 matches were confirmed by SMRT Sequencing had a significantly improved 5-year overall survival of 54.8% compared to 30.1% for those whose 12/12 matches were changed based on higher-resolution information. Furthermore, ultra-high resolution 12/12 HLA matched patients also had significantly higher five-year overall survival (55.1%) than those patients with any degree of mismatching (40.1%).

The study also showed that perfectly matched patients were less likely to die of other transplant-related complications in the 12 months post-transplant, and significantly less likely to develop acute graft-versus-host disease. The study highlights the importance of sequencing through previously uncharacterized regions of the traditional HLA genes, showing that polymorphisms in these regions affect patient overall survival.
In a statement about this study, Neema Mayor from the Anthony Nolan Research Institute said: “We believe that HLA matching at ultra-high resolution could ultimately enable us to further minimize the risk of complications such as graft-versus-host disease and, consequently, the risk of mortality — potentially saving more lives in the future.”