Peripheral blood late mixed chimerism in leucocyte subpopulations following allogeneic stem cell transplantation for childhood malignancies: does it matter?

The impact of persistent mixed chimerism (MC) after haematopoietic stem cell transplantation (HSCT) remains unclarified. We investigated the incidence of MC in peripheral blood beyond day +50 after HSCT and its impact on rejection, chronic graft-versus-host disease (c-GvHD) and relapse in 161 children receiving allogeneic HSCT for haematological malignancies. The 1-year incidence of late MC was 26%. Spontaneous conversion to complete donor chimerism (CC) occurred in 43% of patients as compared to 62% after donor lymphocyte infusions. No graft rejection occurred. The 1-year incidence of c-GvHD was 20 +/- 7% for MC, and 18 +/- 4% for CC patients (P=0734). The 3-year cumulative incidence of relapse (CIR) according to chimerism status at days +50 and +100 was 22 +/- 4% for CC patients vs. 22 +/- 8% for MC patients (day +50; P=0935) and 21 +/- 4% vs. 20 +/- 7% (day +100; P=0907). Three-year CIRs in patients with persistent MC and patients with CC/limited MC were comparable (8 +/- 7% vs. 19 +/- 4%; P=0960). HSCT for acute leukaemia or myelodysplastic syndrome as secondary malignancies (hazard ratio (HR) 47; P=0008), for AML (HR 30; P=002) and from mismatched donors (HR 31; P=003) were independent factors associated with relapse. Our data suggest that late MC neither protects from c-GvHD nor does it reliably predict impending disease relapse.