Authors:
Dr Mary Eapen MRCPI, Prof John P Klein PhD, Guillermo F Sanz MD, Stephen Spellman MS, Annalisa Ruggeri MD, Prof Claudio Anasetti MD, Maria Brown BS, Prof Richard E Champlin MD, Joan Garcia-Lopez MD, Gareth Hattersely, Prof Gesine Koegler MD, Prof Mary J Laughlin MD, Prof Gerard Michel MD, Samir K Nabhan MD, Prof Franklin O Smith MD, Prof Mary M Horowitz MD, Prof Eliane Gluckman MD, Vanderson Rocha MD, for the Eurocord-European Group for Blood and Marrow Transplantation, Netcord, and the Center for International Blood and Marrow Transplant Research
Summary:
Background - The importance of matching at the HLA C locus has not been well defined for unrelated umbilical-cord blood transplantation. The selection algorithm for umbilical-cord blood units generally considers intermediate resolution HLA typing at A and B and allele-level typing at DRB1. We aimed to establish the relative importance of additional matching at HLA C.
Methods - We used Cox regression to assess retrospectively the effect of donor—recipient HLA matching on outcomes of single umbilical-cord blood transplantations for leukaemia and myelodysplastic syndrome. Our primary endpoint was transplant-related mortality. HLA typing was done with molecular techniques with a minimum of intermediate resolution for HLA A, B, and C, and at the allele-level for DRB1.
Findings - The median age of our study population was 10 years (range <1—62) and 552 (69%) of 803 patients were aged 16 years or younger at transplantation. Compared with transplantations matched at HLA A, B, C, and DRB1 (n=69), transplant-related mortality risk was higher after transplantations matched at HLA A, B, and DRB1 and mismatched at HLA C (n=23; HR 3•97, 95% CI 1•27—12•40; p=0•018). Transplant-related mortality risk was also higher after transplantations with a single mismatch at HLA A, B, or DRB1 and mismatched at HLA C (n=234; 1•70, 1•06—2•74; p=0•029) compared with transplantations matched at HLA C with a single mismatch at HLA A, B, or DRB1 (n=127). Assessing the overall effect of HLA disparity on transplant-related mortality, risks were higher with units mismatched at two (n=259; 3•27, 1•42—7•54; p=0•006), three (n=253; 3•34, 1•45—7•71; p=0•005), or four (n=75; 3•51, 1•44—8•58; p=0•006) loci compared with matched units (n=69).
Interpretation - Our data suggest that the present strategy for umbilical-cord blood unit selection should be reassessed; matching at HLA C for units that are matched at HLA A, B, or DRB1 or in the presence of a single locus mismatch at HLA A, B, or DRB1 should be included to minimise mortality risks.
Source:
The Lancet Oncology; Vol. 12, Issue 13, 1214-1221 (12/11)