Myeloid mixed chimerism is associated with relapse in bcr-abl positive patients after unmanipulated allogeneic bone marrow transplantation for chronic myelogenous leukemia

Background and Objectives. Although bcr-abl polymerase chain reaction (PCR) positivity after bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) is significantly related to relapse, the predictive value o f the assay is not very high and therefore most investigators consider that qualitative RI-PCR data alone are too imprecise to enable clinical decisio ns to be taken in individual cases. To define the clinical outcome of bcr-a bl positive patients after unmanipulated BMT better, we sought the origin o f hematopoiesis and traced its evolution over time. Design and Methods. Forty-nine patients received allogeneic BMT for CML (39 in chronic phase and 10 In accelerated phase/blast crisis). Median follow- up was 61 months (range 4-92). mRNA and DNA were used to assess bcr-abl and chimerism status respectively. Quantitative VNTR-PCR on total cells and ly mphoid or myeloid population allowed us to assign and measure the origin of hematopoiesis. Results. Both bcr-abl positivity and the presence of mixed chimerism (MC) w ere significantly associated with relapse (p = 0.0009 and p < 0.0001 respec tively). Relapse was observed in one of 39 patients with complete donor chi merism and in 6 of 9 patients with MC. These six cases showed increasing le vels of host hemopoiesis and bcr-abl positivity in the CD15-positive popula tion prior to relapse. The other three cases had decreasing or stable low-l evel MC which was restricted to the T-cells as well as bcr-abl negativity. Interpretation and Conclusions. Whereas the simple detection of bcr-abl fai ls to identify patients who will relapse with certainty, the assessment of MC by VNTR-PCR does identify patients headed to relapse. Confirmation of my eloid involvement and increasing levels over time further elucidates the cl inical outcome of bcr-abl positive patients after BMT. (C) 2000 Ferrata Sto rti Foundation.