Chimerism in blood after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia: Results from a cohort study.

[BACKGROUND] Allogeneic hematopoietic stem cell transplantation (HSCT) is still a curative option in acute myeloid leukemia treatment (AML) owing to a long-lasting graft-versus-leukemia effect. Relapse remains its major cause of failure. Preemptive strategies based on biological markers for impending relapse have been proven with better outcomes than salvage treatment.

[METHODS AND FINDINGS] We investigated chimerism-based preemptive immunomodulation in 90 HSCT patients with AML. Primary endpoint was relapse risk assessment by real time quantitative PCR (q-PCR) chimerism monitoring in blood. Post-HSCT unfractionated peripheral blood (PB) and bone marrow (BM) samples were timely collected for q-PCR assays. Increasing mixed chimerism (IMC) was defined as a significant increase of percentage of recipient-derived cells between two consecutive samples. Patients were stratified into three groups: no IMC, one IMC with no further IMC and two consecutive IMC. Preemptive immunomodulation (fast tapering of immunosuppressive treatment and/or donor lymphocyte infusion) was triggered by the first documented IMC, and 2 consecutive IMC triggered minimal measurable disease assessment. PB assays compared favorably with BM in our cohort. The risk of relapse was higher in patients with two consecutive IMC (SHR 2·9, 95 % CI: 1·4 - 6·0, p = 0·005) and overall survival was shortened (HR 2·2, 95 % CI: 1·01 - 4·7, p = 0·048).

[CONCLUSION] Serial monitoring of q-PCR chimerism in PB may be a relevant tool for impending relapse detection in post-HSCT acute myeloid leukemia.