The Balance in Chimerism between T Cells and Blood Dendritic Cells in Relapsed CML Patients Influences the Induction of Alloreactivity Following Donor Lymphocyte Infusion.

Abstract

Donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation induce complete remissions in 70 to 80% of patients with relapsed CML in chronic phase, but some patients do not respond sufficiently to DLI. We studied chimerism in subsets of immune cells in relation to the induction of alloreactivity. T cells and two subsets of DC (blood precursor myeloid dendritic cells [MDC] and blood precursor plasmacytoid dendritic cells [PDC]) were isolated from 15 relapsed CML-patients shortly before DLI for chimerism analysis. Furthermore, the absolute blood counts of DC-subsets were determined. Based on chimerism we identified three groups. Group 1 (4 patients) was complete donor chimeric in T cells and DC-subsets. These patients had an early stage of relapse and 3 of 4 patients attained a complete molecular remission (mCR) without significant GVHD. Group 2 (6 patients) was complete donor in T cells and mixed chimeric in DC-subsets. Median percentage of recipient MDC in 4 patients with mixed chimerism was 67% (range, 36%–72%). One patient was complete donor and one patient complete recipient chimeric in MDC. Median percentage of recipient PDC was 37% (range, 18%–58%) in 5 patients with mixed chimerism and in 1 patient PDC were complete recipient derived. All patients entered mCR, however in combination with GVHD in 4 and bone marrow hypoplasia in 3 patients. Group 3 (5 patients) had mixed chimerism in T cells and complete recipient chimerism in MDC in 4 of 5 patients. Only 2 patients entered mCR. Absolute DC numbers at the time of DLI did not predict the induction of an allo-immune response, however very low numbers of MDC and PDC were associated with progressive disease and a poor outcome. The combination of donor chimerism in T cells and mixed chimerism in DC-subsets in advanced relapse is associated with the most potent GVL effect following DLI. GVL and GVHD are separated in patients with an early relapse and donor chimerism in both T cells and DC-subsets. Finally, absolute DC numbers do not predict the strength of the alloresponse.