High Engraftment Rates Following Second Allogeneic Transplants for Graft Failure Result in Good Outcomes, On Behalf of the BSBMT

Graft failure is a highly unsatisfactory outcome of allogeneic transplant. Several factors have been identified which may predict for graft failure, however factors influencing the success of a second allogeneic transplant in this setting are not well studied.
METHODS
The BSBMT analysed 130 patients receiving a second allogeneic transplant for graft failure. Patients were identified from the BSBMT Data Registry and transplant centres were approached to provide follow up data.
RESULTS
The median age of patients was 9 (range 4m-69), with 53 (40%) being adults (>18). The disease was malignant (47%) or non-malignant (53%). The majority of patients had conditioning for the second transplant (68%), which included serotherapy (Alemtuzumab/ATG) in almost all cases. This was myeloablative (30%) or reduced intensity (39%) (compared to 56% and 43%, respectively, at first transplant). The donor was a sibling (24%), unrelated donor (58%) or other relative (18%). In 74% the same donor was used. The stem cell source was bone marrow (41%), PBSC (54%), both (2%) and UCB (3%) (compared to 53%, 38%, 1% and 7%, respectively, at first transplant). Stable engraftment occurred in 88% of patients following the second transplant. Factors associated with a significant increase in engraftment failure were older age (p=0.003), male recipients (p=0.025), reduced intensity conditioning (compared to myeloablative or none) (p=0.031), the use of a different donor (p=0.026) and transplant for a malignant diagnosis (p=0.005). Age (HR=11.52, p=0.001) and the use of a different donor (HR=8.17, p=0.003) remained significant in the multivariate analysis. The donor type, stem cell source and the time post first transplant did not impact on engraftment. Overall survival was 60% at 5 years in the entire group. OS was significantly worse in adult patients (37% vs 74%, p<0.0001), those with malignant disease (40% vs 78%, p=0.0001) and those transplanted beyond 3 months after the first transplant (47% vs 65%, p=0.02). No other factors tested were significant, and only malignancy remained significantly associated with OS in multivariate analysis (HR=2.53, p=0.018).
CONCLUSION
These encouraging results suggest that successful engraftment and long term survival is possible following a second transplant for graft failure. Although outcomes are superior in children and those with non-malignant disease, over a third of adult patients and those with malignant diseases can also achieve long term survival.