Molecular monitoring of minimal residual disease in two patients with MLL-rearranged acute myeloid leukemia and haploidentical transplantation after relapse

Acute myeloid leukemia (AML) is a molecularly heterogeneous disease. Around 5–10% of affected patients show MLL translocations and an additional 8% have a MLL partial internal duplication. While MLL aberrations have historically and generally been associated with an adverse prognosis, this view has become more differentiated during recent years and at least for some rarer MLL aberrations this verdict appears to be unfounded [1]. The 5 most common MLL aberrations in adult AML are t(9;11)/MLL-AF9, t(6;11)/MLL-AF6, t(11;19)/MLL-ELL, t(11;19)/MLL-ENL, and t(10;11)/MLL-AF10, together accounting for around 80% of cases [2,3]. The general recommendation for younger and medically fit AML patients is allogeneic transplantation. The only exception are the core-binding factor leukemias with either CBFA2-ETO or CBFB-MYH11, and acute promyelocytic leukemia with PML-RARA, if no additional high-risk features (e.g. FLT3-ITD) are present. Around 15–30% of patients referred for transplantation have a suitable HLA-identical sibling donor. Large donor registries can be accessed for those patients without a HLA-identical sibling donor, but the likelihood of finding a suitable donor depends strongly on the ethnic background of the patient [4]. Currently it is possible to identify a suitable HLA-identical donor in around 70% of patients of European ancestry [5]. Different options exist for those patients without a fully (10/10) HLA antigen-matched donor. Clinical trials with donors showing only a 9/10, 8/10 or even 7/10 HLA match have shown a significantly higher transplant-related mortality, mainly due to the higher incidence of severe graft-versus-host disease (GvHD) [6-8]. The Perugia group of Martelli and coworkers first introduced the concept of transplanting “megadoses” of highly purified CD34+ cells of a HLA-haploidentical donor in the clinical setting to overcome the HLA barrier and prevent graft failure [9,10]. To achieve an alloreactive antileukemic effect in the absence of allo