The Effect of Donor Characteristics On Graft Vs. Host Disease (GVHD) and Survival After Unrelated Donor Transplantation for Hematologic Malignancy

The Effect of Donor Characteristics on Graft vs. Host Disease (GVHD) and Survival after Unrelated Donor Transplantation for Hematologic Malignancy

Craig Kollman, John Klein, Stephen Spellman, Anna Hassebroek, Dennis Confer, Marcelo Fernandez-Vina, Robert Hartzman, Carolyn K Hurley, Martin Maiers, Carlheinz Mueller, Michelle Setterholm, Ann Woolfrey, Neng Yu and Mary Eapen on behalf of the NMDP Histocompatibility Advisory Group

We analyzed 6,349 adult unrelated donor transplantations performed in 1988–2006 to reexamine the effect of donor age and other donor characteristics including donor-recipient HLA matching on transplant outcomes.  Patients had a hematologic malignancy (ALL, AML, CML, MDS) and approximately 40% were in first complete remission or first chronic phase.  93% of transplantations used donors younger than 50 (median 35.8, range 18-61).  The majority of patients received myeloablative preparative regimens (88%) and bone marrow grafts (62%).  All patients received calcineurin inhibitor containing GVHD prophylaxis and 20% received in vivo T cell depletion. We identified three donor characteristics associated with overall survival; donor age, high resolution donor-recipient HLA-match and ABO blood group match (table).  Risk adjusted 5-year survival rates were 37%, 33% and 29% with donors aged 18-32, 33-50, and >50 years, respectively (p<0.0001).  Corresponding hazard ratios were 1.13 (p=0.0004) for donors aged 33–50 years and 1.29 (p<0.001) for donors >50 years compared with donors aged 18 – 32 years.  Mortality risks were higher with one (HR 1.24, p<0.0001) and two (HR 1.62, p<0.0001) HLA-mismatches compared with HLA-matched transplants and minor (HR 1.10, p=0.002) or major (HR 1.13, p=0.001) ABO blood group mismatch compared with ABO-matched transplants.  A sub-analysis investigated the possibility that the association with donor age may be due to underlying genetic disparity between donor and recipient. That is, recipients with rare HLA genotypes tend to have fewer matched donors to choose from and thus more likely to receive a graft from an older donor.  Recipient genotypes were assigned to quartiles using frequency data from 4 million NMDP donors as a reference. The lowest frequency quartile was associated with donors older than 50 (p<0.0001) and higher rates of HLA mismatching (p<0.001) but no association was found between genotype frequency and overall mortality.  Acute GVHD risks were associated with donor age and HLA match and, donor parity, the only donor characteristic associated with chronic GVHD (table).  In summary, the data recommend the consideration of donor age and ABO blood group match to maximize survival when selecting among comparably HLA-matched adult unrelated stem cell donors for treatment of a hematologic malignancy.