Donor lymphocyte infusions after reduced intensity conditioning allogeneic transplantation: what we need to know.

Donor lymphocyte infusions after reduced intensity conditioning allogeneic transplantation: what we need to know Recently in Blood there were 2 papers that increased our knowledge about donor lymphocyte infusions (DLIs) given after reduced intensity conditioning transplantation. 1,2 We published a United Kingdom national study in 81 similar patients 19 months ago. 3 This study had a number of limitations mainly because there were multiple different conditioning regimens and the reasons for giving DLIs varied from patient to patient. In concluding, we suggested that there should be prospective randomized studies to address the major questions. Both of the new published studies have the advantage of uniform conditioning regimens and more complete multilineage chimerism data, but many questions remain. A recent example perhaps best illustrates the gaps in our knowledge. A colleague contacted us about an adolescent patient with acute myeloid leukemia who received a nonmyeloablative unrelated donor transplant, having relapsed after the first full intensity transplant from the same donor. At a few months after transplantation, she had only 70% to 85% donor chimerism in T cells and myeloid cells. Given that the patient was at such high risk of relapse, an interventional strategy seemed justified, but it was hard to advise about the need for DLI and the chance of conversion to full donor chimerism, the starting dose of T cells, the chance of lethal acute or chronic graft-versus-host disease (GVHD), and the likelihood of reducing relapse risk with DLI. First, is it necessary to convert a state of stable mixed chimerism to full donor chimerism in the absence of measurable disease? While intuitively the answer is yes, particularly in cases considered to be at high risk of relapse, the recent studies do not provide data regarding the natural history of stable mixed chimerism in the absence of DLIs. 1-3 Mixed chimerism can be stable and can be associated with GVHD and a graft-versus-malignancy (GVM) effect. 4 In some studies 1,3 there does appear to be an association between disease response and conversion to full donor chimerism following DLI, but this is not a universal finding. 2,4 These studies also demonstrate that conversion to complete donor chimerism following DLI cannot be guaranteed, occurring in 34% to 82% of patients. 1-3 This question becomes more critical in the unrelated donor setting where the incidence of GVHD following DLI may be higher 2 and lower starting doses may be required. If we …