The Presence Of 1 / 8 HLA Mismatch Do Not Hamper Survival After Allogeneic Stem Cell Transplantation Using Immunoprophylaxis With Sirolimus-Tacrolimus

Several studies from the IBMTR have shown that overall survival (OS) is reduced by 10% for each mismatched at obligatory locus (A,B,C or DRB1) after allogeneic hematopoietic stem cell transplant (Allo-HSCT) (Lee et al. Blood 07). In the setting of 7/8 mismatched allo HSCT, different T-cell depletion strategies are frequently used in an attempt to decrease GVHD assuming a higher risk of infections and relapse. Data from the IBMTR are mostly based on series of patients who received Cyclosporine /Tacrolimus (TKR) plus methotrexate as immunoprophylaxis. As far as we know, the effect of sirolimus (SRL)/TKR combination on overall outcomes of transplant, regardless HLA mismatched, has not yet been evaluated.

With this background, we retrospectively analysed a series of 151 adult patients who received SRL/TKR based reduced intensity (RIC)-alloHSCT in 6 Spanish centres, from January 2007 to September 2012 (median follow up in alive patients 19 months, range 4-47), comparing overall outcomes according HLA compatibility in obligatory locus A,B,C, DRB1: 8/8 (n:129) vs 7/8 (n:22). No in vivo or ex vivo T depletion was used.

Patients characteristics are not significantly different between both groups. Median age was 53 years (17-70) and the two most common diseases (56% of cases) were AML and NHL. The most frequent stem cell source was peripheral blood (94%) and 76% transplants were from volunteer unrelated donors. Forty nine per cet of patients had active disease at the time of transplant.

Comparing 8/8 vs 7/8 alloHSCT, non statistically significant differences were found in 3 years-OS (56,4% vs 69%, p=0.7), 1 year-non-relapse mortality [12 % (7-20) vs 14% (5-42), p=0.8], and 3 year-relapse rate: 28% (19-43) vs 20% (9-50), p=0.8, respectively. Cumulative incidence of acute GVHD was significantly higher in 7/8 alloHSCT [68% (49-94) vs 41% (32-51), p=0.004] but no differences were observed with respect to neither III-IV acute GVHD (5 vs 9%, p:0.6) nor global (35 vs 51%, p=0.6) and extensive (20 vs 30%, p=0.9) chronic GHVD in 8/8 vs 7/8, respectively.

The present study shows favorable outcomes of SRL/TKR combination in the setting of RIC alloHSCT, with an overall survival in the range of 55-70%%, and non significant differences in overall outcomes regardless the presence of any mismatched at obligatory locus. Comparative studies with a larger sesries is desirable to confirm these results.