Posted by Attila Berces

Cyprus was an ideal site for a conference on marrow donor registries since this country has the highest proportion of its population HLA typed and registered as donors. The importance of this registry was already apparent on the flight to the conference since Cyprus Airways in-flight magazine featured the history and mission of the Karaiskakio Foundation, which operates the Cyprus Bone Marrow Donor Registry. As is the case with several other registries, it was started with a young boy’s fight with leukemia that mobilized family, friends and the general public after becoming aware how difficult it was to find a match. Today, Cypriotes reached high level of awareness of the importance of becoming a registered marrow donor and developed a financially sustainable model of operations for their registry. It is a significant achievement since only the largest registries can sustain their operations from the fees received for facilitating transplants. Small and medium size registries lack the economy of scale and face the challenge of financial sustainability. HLA genetic diversity is at the root of many economic issues and this conference addressed these questions in their complexity. The conference included lectures on international donor exchange, economic analysis of the ideal registry size and quality, new technologies bringing down the cost of HLA typing, the pros and cons of on-line registration, and social media as a way for attracting donors.

I particularly enjoyed Carlheinz Muller’s presentation about the ideal registry size. He developed elaborate economic models based on recruitment cost, donor lifetime, donor retention cost, number of patients treated, cost of search, survival of patients and the most controversial factor, the value of additional disease-free life. This model was intended to understand the different factors and not necessarily to give an absolute recommended optimal number of donors.  Even with a registry of 10 million in the German population of 80 million significant portion of the population would not be represented by their HLA types. In fact adding the second million donor to the pool of the first million would increase the chance for successful donor search from 50 to 57%. Large registries have a diminishing return for their additional recruitments. Small registries, however, can hardly reach significant enough representation of their population and reach to point of becoming sustainable.

Alexander Schmidt from DKMS discussed the effect of quality of the registry on successful donation. He examined the effect of the level of HLA typing on donor search success.  Fully typed (A, B, C, DRB1, DQB1) donors have higher donation probabilities and thus he concluded that investment in donor retyping with higher resolution technology normally pays off. Convincing donors is more challenging than HLA typing and with NGS the cost of HLA typing is becoming more and more economical.

The conference had an impressive set of presentation from organizations adopting next generation sequencing for HLA typing. Histogenetics  added 22 MiSeq sequencers to their workflow which uses the combination of Sanger and NGS churning out HLA types in unprecedented volumes. DKMS increased its MiSeq capacity to 30 instruments. Both Histogenetics and DKMS sequence only the exons encoding the antigen recognition sites.  Todd Laird presented Life Technologies’ vision of moving to NGS and how their company will address customers’ need of throughput, resolution, capital budget and a range of other factors they considered in the design of their solution. Dimitri Monos presented results of his long-range PCR method for the full characterization of HLA genes using a shotgun sequencing approach on the MiSeq. He reached 99.2% accurate allele calls without ambiguity with his protocol and the Omixon Target software.

This conference provides more evidence for the deep penetration of NGS for HLA typing in the largest labs. The smaller labs that do not have the internal capabilities to develop the NGS library preparation and need to have the full solution including the HLA primers, library prep reagents, barcodes and analysis software available in a single package to enjoy the benefit of NGS. Several vendors are developing such a solution which is going to be the most exciting development for HLA labs in the next years to come.