Development of chronic graft vs host disease (cGvHD) and maintained complete remission at day 100 post-transplant (CR day 100) are associated with improved survival post-allogeneic transplant in acute myeloid leukemia (AML) patients. However, earlier prognostic markers could be beneficial in guiding clinical management post-transplantation. As survival is associated with successful engraftment and B cells play a positive role in cGvHD, we investigated serum free light chain (FLC) measurements, as markers of B cell activation, to determine if they provide prognostic information before day 100 post-transplant.
Serum FLCκ and FLCλ (Freelite®, The Binding Site Group Ltd, Birmingham UK) concentrations were measured retrospectively in stored sera from 42 AML patients at 5 weeks post-transplantation (wk5). FLCκ and FLCλ results were summated to give a combined FLC (cFLC) value, which was assessed with respect to cGvHD and 2 year survival. All statistics were performed using SPSS v21.0. At wk5 median cFLC levels were 17.9mg/L (range: 1.7-53.3).Age at transplant ranged from 19-71 years (median: 53); male/female ratio was 23/19. 27/42 (64%) were transplanted at CR1, 12/42 (29%) at CR2 and 3/42 (7%) at CR3. A myeloablative (MA) conditioning regimen was used in 13/42 (31%) patients; 29/42 (69%) received reduced intensity conditioning (RIC). 21/42 (50%) developed acute GvHD (aGvHD), 18/42 (43%) developed cGvHD and the 2 year mortality rate (MR) was 43% (18/42).
Development of cGvHD (HR 3.2, p=0.04) and maintained CR day 100 (HR 56.8, p=0.001) were associated with improved 2 year survival. By comparison, other routinely evaluated markers were not prognostic, including: 1) type of donor (sibling or match unrelated; HR 0.6, p=0.81); 2) CR1 v CR2/3 prior to transplant (HR 1.2, p=0.72); 3) RIC v MA conditioning (HR 1.0, p=0.97); 4) T-cell depletion/Campath therapy (HR 1.0, p=0.89); 5) CMV reactivation (HR 0.8, p=0.66); 6) donor lymphocyte infusion (HR 21.7, p=0.62); 7) donor/recipient gender mismatch (HR 0.6, p=0.47); and 8) aGvHD development (HR 0.2, p=0.57).
At wk5, patients with elevated cFLC levels (>22.6mg/L; top tertile) had a better 2 year survival compared to the lower two tertiles (Cox regression analysis: HR 5.6, p=0.02; Kaplan Meier analysis: >22.6mg/L: n=14 (2 deaths, 14% MR), median 2 year survival not reached (NR);<22.6mg/L: n=28 (16 deaths, 57% MR), median 2 year survival 408 days, p=0.01). However, cFLC measurements at wk5 were not associated with development of cGvHD (HR 1.15, p=0.78). Finally, wk5 cFLC levels stratified patients with a maintained CR at day 100 (cFLC<22.6mgL: n=25 (13 deaths, 52% MR), median 2 year survival: 517 days; cFLC>22.6mg/L: n=13 (1 death, 8% MR), median 2 year survival NR, p=0.009) and tended towards significance in patients who developed cGvHD (cFLC<22.6mgL: n=15 (6 deaths, 40% MR), median 2 year survival: 394 days; cFLC>22.6mg/L: n=6 (0 deaths), median 2 year survival NR, p=0.09).
Our data suggests assessment of cFLC levels at wk5 post-transplantation provides prognostic information in patients with AML, irrespective of maintained response post-transplantation and cGvHD development. Further studies are needed to confirm the utility of this observation
Young:The Binding Site Group Ltd: Employment. Adie:The Binding Site Group Ltd: Employment. Harding:The Binding Site Group Ltd: Employment.
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