Full Donor T Cell Chimerism Predicts Transplant Outcomes In High Risk AML But Not In Intermediate Risk AML After a T-Deplete Alemtuzumab Conditioned Transplant

Reduced intensity conditioning (RIC) T-deplete regimens are now widely used as a platform to deliver a potentially curative T cell mediated graft-versus-leukaemia (GVL) effect in patients with haematological malignancies. T cell chimerism has been shown to correlate with the risk of both GVHD and disease relapse in T replete RIC AML allografts but it remains unclear whether such a correlation exists in patients undergoing an alemtuzumab based allograft for intermediate and high risk AML.

We have therefore correlated T cell chimerism on D+60 and D+180 in 43 patients undergoing an alemtuzumab based RIC allograft for AML(high risk=20, intermediate risk=23) in CR1 with transplant outcomes. The conditioning used was Fludarabine 30mg/m2 for 5 days, Melphalan 140mg/m2 for 1 day and Alemtuzumab 30mg IV for 1 day for sibling transplants and 50mg IV over 2 days for unrelated donor transplants. The median age of the patients was 51 years (range 42-57 years) and median follow up was 45 months (range 6 – 108 months).18 patients received a graft from a sibling donor and 25 from an unrelated fully matched donor. The 3 year overall survival was 53% on the intermediate risk group and 40% on the high risk group. Overall 31% of patients relapsed in both groups.

T cell full donor chimerism at D+60 and D+180 was significantly associated with better overall survival (52 months vs 18months p:0.04), 2 years disease free survival of (53% vs 32% p:0.03) and higher incidence (85%) of acute GvHD (p:0.01) and chronic GvHD(p:0.02) in the high risk AML group on both univariate and multivariate analysis. In the intermediate risk group though full donor chimerism was associated with improved disease survival on univariate analysis but this wasn’t confirmed on multivariate analysis and this was likely secondary to the small number of patients. In both univariate and multivariate analysis patients with full donor chimerism at 60 days were almost 80% more likely to have acute GVHD than patients with fully donor chimerism (p=0.04) and patients with full donor chimerism at D+180 were almost 85% more likely to achieve chronic GvHD(p:0.02).

Preemptive DLI infusion for mixed chimerism post D+180 was given to patients without prior severe GvHD after stopping Ciclosporin and was associated with improved disease free survival and a trend for improved overall survival for both risk groups by potentially augmenting the GvL effect. The 2 year incidence of graft-versus-host disease post DLI was only 29%.

Although conclusions of our study were limited by the small number of patients included, the high risk AML group of patients seems to benefit from acquisition of full donor T cell chimerism. In the intermediate risk group this effect was not demonstrated although probably a higher number of patients with molecular risk stratification is needed.