A landmark study published Online First in The Lancet Oncology , describes the discovery of a unique matching mechanism that affects the outcome of blood stem cell transplants and helps improving survival rates for sufferers from leukemia and other blood cancers.
Often, the last glimmer of hope for blood cancer sufferers who remain unresponsive to all other treatment options is to receive blood stem cells, also called haemopoietic cells, from an unrelated, living donor.
An allele is an alternative form of a gene, i.e. one member of a pair that is located at a specific position on a specific chromosome. Doctors look for matches of the human leukocyte antigen (HLA) type of five key alleles that occur in a blood stem cell to achieve a 10/10 match to reduce the risks linked to transplants, such as acute Graft versus Host Disease (aGvHD). However, due to complex reasons that are not fully understood, even a 10/10 match does not guarantee a successful transplant.
Research leader Dr. Bronwen Shaw, Clinical Senior Scientist at the blood cancer charity Anthony Nolan and her collaborator Katharina Fleischhauer from the San Raffaele University in Milan have discovered a hidden role of an additional allele (HLA-DPB1) that gives new insight on transplant outcomes.
Researchers previously thought that DPB1 had not impact on transplant outcomes, as it is not often matched between donor and patient. However, the new study has revealed that it is possible to have good, i.e. permissive and bad, i.e. non-permissive DPB1 matches that can have a significant impact on transplant outcomes.
The International Histocompatibility Working Group team retrospectively assessed 5,428 transplants with a 10/10 match, discovering that 20% of these or 1,719 transplants were HLA-DPB1 matches, with 31% or 2,670 transplant being permissive mismatches and 49% or 4,150 transplant being non-permissive mismatches.
Non-permissive mismatches were linked to a substantially increased risk of overall mortality and severe aGvHD as compared with permissive mismatches.
Dr. Bronwen Shaw, Clinical Senior Scientist at Anthony Nolan, stated:
"These findings provide a practical, clinical strategy for lowering the risk of death following an unrelated-donor blood stem cell transplant. It builds on the gold-standard which already exists for transplants and could be easily incorporated into the current framework transplant centers use when trying to find the best match."
The team also established that DPB1 is a potential indicator of transplant outcome in cases where a 10/10 match cannot be found. In such incidents, doctors sometimes use a donor with a 9/10 match, especially if the patient is likely to die unless a transplant is performed quickly.
Chief Executive of Anthony Nolan, Henny Braund concluded:
"This research is incredibly exciting. Anthony Nolan created the world's first stem cell register in 1974. Since that time, we have been committed to saving as many lives as possible through a combination of providing matches through our register and exploring the science behind transplants to improve survival rates. This study provides a genuine breakthrough in a very complex scientific area and will undoubtedly help save many more lives in the future."
Written by Petra Rattue