A prospective molecular study of chimaerism in patients with haematological malignancies receiving unrelated cord blood or bone marrow transplants: detection of mixed chimaerism predicts graft failure with or without early autologous reconstitution in cord blood recipients

We prospectively studied the chimaerism status in the bone marrow (BM) and peripheral blood (PB) of 23 patients receiving umbilical cord (UCB, 14 case s) or BM (nine cases) transplants from unrelated donors by PCR amplificatio n of four individual-specific VNTR genetic loci. Haematological engraftment , with persistent full donor pattern, was observed in 10/14 (72%) patients receiving UCB and in 9/9 (100%) patients transplanted with marrow from an u nrelated donor (MUD). In contrast, the remaining four patients converted to an autologous pattern. Three out of these four patients had an earrq autol ogous haematological reconstitution reaching a neutrophil level >0.5 x 10(9 )/l at days 27, 33 and 37 after transplant, respectively In all three of th ese patients, chimaerism analysis demonstrated an early appearance of donor cells (i.e. within 35 d after UCB transplant) showing a transient full don or (one case) or mixed chimaerism condition (two cases). Despite the early autologous haemopoietic reconstitution, one of the three patients died of G VHD at day 60, which was explained by the demonstration of low levels of do nor lymphoid cells. In the MUD group all nine patients converted to a persi stent full donor pattern with haematological reconstitution, accompanied in two of them by transient mixed chimaerism lasting to days 60 and 270 after transplant. Our data show that monitoring of chimaerism may predict graft failure with or without early autologous haemopoietic reconstitution in pat ients receiving unrelated CCB transplants. Furthermore, chimaerism analysis may identify in patients with autologous reconstitution, those at risk of severe GVHD in whom immunosuppressive therapy should not be discontinued.