Minimal residual disease status in pre-B acute lymphoblastic leukemia patients after chemotherapy and bone marrow transplantation: assessment of the anti-leukemic effects of chemotherapy and BMT.

We prospectively analyzed minimal residual disease (MRD) in four patients with B-cell precursor acute lymphoblastic leukemia who had been in complete remission for more than one year after chemotherapy and allogenic or autologous bone marrow transplantation (BMT). MRD was quantitatively estimated using polymerase chain reaction amplification to detect the complementarity-determining region III of the immunoglobulin heavy chain gene at limiting dilution DNA samples. Our study showed that remission induction chemotherapy reduced at most 2-logs of leukemia cells, and that subsequent consolidation chemotherapy induced further reduction of leukemia cells. In two cases, 10(-5) levels of MRD were detected two months after BMT. However, no MRD was detected four months after BMT. We also showed the effectiveness of ex vivo purging with anti-CALLA monoclonal antibodies which eliminated at least 2-logs of leukemia cells in autologous BMT. Our results suggest that this detection system is useful for assessing the reduction of the original leukemia clone, and that the presence of MRD within three months after BMT is not related to clinical outcome.