Matched Unrelated Donor Transplantation
The options for alternative donor were limited by the initial studies demonstrating the primacy of HLA matching in dictating the outcome of BMT. The chances of finding a HLA match within the extended family are remote and even more so from an unrelated donor. However, in 1973, random searches through Blood Bank database in Denmark led to the identification of a HLA matched donor for a patient in the USA with immunodeficiency.
In 1979, Laura Graves, a patient with leukemia, was referred to the Fred Hutchinson Cancer Centre. Laura did not have a matched donor in her family, so,centre staff searched through their database of platelet donors in an attempt to find a match. Luckily, one of the laboratory staff turned out to be a good match. Laura's transplant was successful, and she did not develop graft-versus-host disease (GVHD). Although Laura died two years later of recurrent leukemia, the Graves family continued to lead an effort to establish a national registry of people volunteering to be bone-marrow donors. The National Bone Marrow Donor Registry was federally funded in 1986, and in 1987 the first donor match was made. In 1988, the name was changed to the National Marrow Donor Registry (NMDP). The NMDP now includes a network of donor registries in 30 countries. Its database contains more than 5.5 million donors and facilitates an average of 200 transplants each month. Several such registries are operational in all developed countries accounting for over 10 million donors worldwide.
Outcome of Unrelated Donor BMT
At the inception, Unrelated Donor BMT was an extremely high risk procedure with a Transplant Related Mortality (TRM) of nearly 50%. The major causes of mortality were GVHD and infections. Large registry based studies demonstrated the adverse impact of even single allele mismatch at HLA A,B,C or DRB1 on the outcome of UDBMT. This is more apparent in early stage disease and the adverse impact was balanced by a more pronounced graft-versus-leukemia (GVL) effect in advanced leukemia.
With improvement in supportive care and advancing knowledge in GVHD and post-transplant infections, TRM has reduced from 30% to less than 10% in HLA matched sibling transplants. The same is reflected in UDBMT as well with TRM being reduced to less than 30%. In the latter, this is largely attributable to improved HLA typing resulting in more perfect match.
The source of HPC is furthermore no longer limited to bone marrow. The use of growth factor mobilised peripheral blood HPC (PBHPC) contribute to the majority of transplants in 2011. In the last three years 50% of all BMT undertaken worldwide employed the latter as the source of unrelated grafts. Donor as well as recipient issues have been instrumental in this shift in the source of grafts, both related and unrelated. PBHPC donation does not involve general anesthesia as in bone marrow harvest and rarely requires hospitalisation. There was an initial concern and ethical dilemma regarding the use of hematopoeitic growth factors in unrelated donors. However, cumulative experience in related donors was reassuring enough to initiate the use of mobilised PBHPC from unrelated donors. As regards the recipient, engraftment is definitely more rapid with PBHPC with probably a superior outcome in advanced leukemia.
Several observational studies over the last decade showed near equivalent outcome for both related and unrelated donors. This has resulted in a paradigm shift in the position of UDBMT in the treatment algorithm for haematological malignancies. From being the final resort for patients with advanced leukemia with no related donor to the treatment of choice for early stage diseases, both malignant and non-malignant, UDBMT has come a long way since the battle launched by Laura Greaves.
However, In India, such registries are in their infancy and the chance of finding a match from the foreign registries is less than 10%. More importantly the cost of procuring the blood or marrow products from Europe or USA ranges from 10,000-30,000 USD, which is the cost of a Haplo-identical BMT itself.