Persistence of BCR-ABL genomic rearrangement in chronic myeloid leukemia patients in complete and sustained cytogenetic remission after interferon-alpha therapy or allogeneic bone marrow transplantation

In recent years, the prognosis of chronic myeloid leukemia (CML) has been g reatly improved either with interferon-alpha (IFN-alpha) therapy or allogen eic bone marrow transplantation (BMT), In the present study, minimal residu al disease was evaluated in 21 patients in complete cytogenetic response (C CR) after such treatments. Samples from bone marrow aspirates or peripheral blood or both were analyzed by conventional cytogenetics, Southern blot, i nterphase fluorescent in situ hybridization (FISH), and quantitative revers e transcription-polymerase chain reaction (Q-RT-PCR). In all patients, FISH detected 1% to 12% nuclei with a BCR-ABL fusion gene, whereas Q-RT-PCR exp eriments were negative or weakly positive. Based on these results, we hypot hesize that the BCR-ABL genomic rearrangement persists unexpressed in nonpr oliferating cells whatever the treatment (IFN-alpha or BMT). These data poi nt to the need for follow-up of CML patients in CCR over an extensive perio d at the DNA level (FISH) to evaluate the residual disease and at the RNA l evel (Q-RT-PCR) to estimate the risk of relapse. (Blood, 2000;95:404-409) a 2000 by The American Society of Hematology.