This case highlights several issues regarding the importance of falling chimerism post transplant and possible therapeutic interventions to reverse it.  The first issue is whether the fall in donor chimerism reflects graft rejection, the presence of recurrent disease, or both.  Some studies have demonstrated that mixed chimerism more commonly occurs early after RIC in patients with myeloid disease compared with patients with lymphoid diseases.¹  It is not clear whether the achievement of high levels of donor chimerism after transplantation is related to the patient’s disease, pre-transplant treatment or the intensity of therapy received for conditioning.  Studies have demonstrated that “low” degrees of donor chimerism early after transplantation are associated with decreased progression free survival in patients with myeloid diseases.^2,3  Specifically, T cell chimerism of less than 50% is associated with a higher relapse rate.²  Serial chimerism analyses showing falling chimerism in patients with AML may also predict relapse.⁴  I would be worried about impending relapse in this patient despite the recent study showing normal morphology and cytogenetics.

There is general agreement that falling chimerism requires intervention.  The majority of respondents (83%) recommended a rapid taper or discontinuation of immune suppressive therapy.  While this would be the course I would recommend, the rate of taper in patients with unrelated or HLA-mismatched donors is often more measured because of the concern for developing severe GVHD.  Continuing with the original taper schedule was recommended by about 8% of respondents, but in many cases the clinical result is unsatisfactory with patients eventually relapsing.  Once off immune suppressive therapy, donor lymphocyte infusion is often pursued as a next step with only partial success in reversing mixed chimerism.⁵  It is not clear that other strategies such as prophylactic DLI while on immune suppressive therapy as suggested by 10% of those responding will reverse the fall in chimerism.  No one voted to increase immune suppressive therapy.

While high levels of donor chimerism are associated with an improved outcome in patients with AML, the best method to achieve high levels early after transplantation and maintain them is under investigation.  Whether maintaining high levels of donor chimerism or reversing falling chimerism results in improved disease control remains unproven, although the close relationship between donor chimerism and outcome in myeloid diseases suggests that there is a common hematopoietic target of the graft versus leukemia reaction.