Prediction of Relapse and Impact of Immunomodulation Based On Quantitative RT-PCR of Insertion/Deletion Polymorphism for Chimerism Analysis in Acute Leukemia

Abstract 1966

Detection of increasing mixed chimerism (IMC) using standard PCR is correlated with relapse after allogeneic stem cell transplantation (allo-SCT) for acute lymphoblastic and myeloid leukemias (AL); however, it is not known whether using a very sensitive method such as quantitative real time PCR of insertion/deletion polymorphism (indel-qPCR) would be of benefit. Here, we studied whether this technique is useful for predicting relapse after transplant for AL, and whether an immunomodulation (IM) based on the detection of IMC would improve outcome. Eighty-nine transplants were included, with a median follow-up of 30 months for the survivors (range 4–86). The 3-year overall survival (OS) was 57.4% (95% CI: 48.1–66.7%). Twenty-one patients relapsed, leading to a 3-year incidence of relapse of 28.9%. An IMC was defined by an increasing of patient's DNA rate of 1 log when it was under 0.1% and an increasing of at least 0.1% beyond this threshold. Among the 57 transplants presented IMC, 21 relapsed, whereas none of the 32 patients with stable or decreasing chimerism relapsed. By multivariate analysis, the detection of IMC and the disease status at transplant were strongly associated with relapse (p=0.0002; HR: 27.6, 95%CI: 3–246 and p=0.0037; HR: 3.4 95%CI: 1.4–8.2, respectively). After the detection of one IMC (n=57), an IM was performed in 27 patients, consisted in withdrawal of immunosuppressive drugs for all, and followed by donor lymphocyte infusion (DLI) in 2. For these 27 patients, the 1 and 3-year relapse rate was 15.7%, versus 57.6% in the 30 other patients (p=0.0007). After IM, 2 patients developed acute graft versus host disease (GVHD) (grade 2 and grade 4) and died of infection. Both of them had received DLI. Four patients presented extensive chronic GVHD and two of them died. Altogether, the 3-year overall survival was 68.3% after IM versus 42.6% without any immunological intervention (p=0.02). These results suggest that chimerism analysis using indel-qPCR is a useful tool to early detect and prevent relapse after allo-SCT for AL.