Sunday, November 27, 2011

Cord-blood disappointment

One of the supposed advantages of cord-blood transplantation is the suggestion that intensive matching is not required. Advocates of this view will be disappointed by this comment in Lancet Oncology

After years of research and debate, findings after umbilical-cord blood transplantation have mirrored those of other sources for haemopoietic stem-cell transplantation—ie, matching of the HLA loci between donor and recipient does matter. Thus cord-blood transplantation now faces the same hurdles as bone-marrow or peripheral-blood stem-cell transplantation. In The Lancet Oncology, in a clear and convincing analysis, Mary Eapen and colleagues1 show that additional matching of donor and recipient for HLA C improved the outcome of patients with a cord-blood transplant. This improvement was identified independently of other known risk factors for outcome after haemopoietic stem-cell transplantation, such as the patient's age or disease stage. Results were based on a homogeneous group of more than 800 patients with leukaemia or myelodysplastic syndrome and with sufficient information for the class I HLA antigens HLA A, B, and C and the class II antigen DRB1 in donors and recipients. Pairs with or without matching for HLA C could be compared with pairs with no, single, or multiple mismatches at HLA loci other than HLA C. Effects of matching for HLA C were greatest when no HLA antigen or only one other HLA antigen differed between the donor and recipient.

The importance of matching for HLA in general was underlined by two additional findings: results were better with full matching than with a single, double, or multiple mismatch at any of the class I or class II antigens; and, in the case of a single mismatch for one class I antigen, results were better when the class II antigens DRB1 were identical.

These findings accord with results from unrelated-donor transplants and are reassuring to immunologists (it was difficult to understand why cord blood should behave differently to other sources). These findings might be disappointing for some who thought minimal matching sufficient, but they have clear consequences. The degree of matching between donor and recipient, including HLA C, needs to be integrated into the algorithm used to select for or against transplantation. The risk of disease should be balanced against the transplant risk, so that overall a better outcome with regard to survival, quality of life, and cost, compared with a non-transplant strategy, is achieved. If cord-blood transplants are to be used in early disease, such as for patients with high-risk acute myeloid leukaemia in first complete remission, the search strategy should aim for the best match and should now include HLA C. The value of high-degree matching in unrelated-donor transplants was recently shown to be specifically important for patients with early disease and low-risk characteristics. Hence, an optimally matched transplant product might tip the balance in favour of immediate transplantation in first remission, whereas a suboptimal product would favour a watch and wait or non-transplant strategy. To allow sufficient time for the selection process, any donor search for an unrelated-living or cord-blood donor needs to be started at diagnosis.

The findings of Eapen and colleagues further support the role of standardised reporting of transplant data, as recently stipulated by the WHO's guiding principles on organ and cell transplantation. Only by such cooperation can results be yielded. Furthermore, other antigens such as HLA DQ, HLA DP, or minor histocompatibility antigens are likely to be important in cord-blood transplants because they are present in unrelated-volunteer donor transplants. Typing for HLA C should now become mandatory, accompanied with storage of samples for later analysis. Cord-blood banks will have to provide this service. The additional costs will be recouped through improved transplant outcomes. Quality management systems such as the Foundation for the Accreditation of Cellular Therapy, the Joint Accreditation Committee: European Group for Blood and Marrow Transplantation and the International Society for Cellular Therapy, or Netcord should implement full typing for class I and II antigens into their standards. These steps will help to further improve the procedure and define those selected patients who will clearly benefit from a cord-blood transplant.


Brian Koffman said...

Hi Terry,

Is this study essentially saying the looser matching requirements for a cord transplant should be a thing of the past?

If so, how did we get it so wrong before?

Be well, my friend


Terry Hamblin said...

It seems to say that better matching gets better results. But perhaps this is a matter of degree and that mismatched cord can still get a result.