Detection of MRD after bone marrow transplantation in chronic myeloid leukemia

CML is incurable using standard chemotherapy, and allogeneic bone marrow transplantation (BMT) remains the treatment of choice for suitable patients. However, 20% of patients transplanted in the chronic phase and more than 50% of patients transplanted in the accelerated phase or blast crisis will relapse. Considerable effort has been made to establish whether persistence of MRD after allogeneic BMT is predictive of relapse. Early studies yielded conflicting results about the clinical implications of persistence of PCR-detectable disease. However, a recent large study from Seattle, including analysis of data from 346 patients, showed a clear association between the relapse and persistence of PCR-detectable disease. Detection of MRD early after BMT does not necessarily suggest a poor prognosis, and a PCR-positive sample 3 months after BMT was not informative for the clinical outcome. In contrast, a PCR-positive BM or peripheral blood sample at or after 6 months post-BMT was closely associated with subsequent relapse. Statistical analysis of the data revealed that the PCR assay for the BCR-ABL fusion transcript 6-12 months after BMT is an independent predictor of subsequent relapse. In contrast, no clear prediction of clinical outcome could be made in patients who tested PCR-positive more than 3 years after BMT. This study and others have clearly demonstrated that most patients are PCR-positive 3 months after BMT, indicating that BMT preparative regimens alone do not eradicate CML cells effectively. Nevertheless, since this treatment leads to cure in more than 50% of patients, other mechanisms, for example immunological mechanisms, must be responsible for tumor eradication.

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