Recurrent disease or donor cell leukemia?: Brain teaser after allogeneic bone marrow transplantation

Allogeneic bone marrow transplantation (allo-BMT) is the treatment of choice for many patients with poor prognosis or refractory leukemia. Chimerism and residual tumor load after allo-BMT are widely monitored to detect impending graft rejection and the early phase of relapse. In most cases, the malignant cell population during post-transplant relapse contains host-derived cells, but the leukemic clone can rarely be of donor-cell origin. Various genetic tests with different strategies, targets and sensitivities are available for donor-host discrimination. However, changes in the genomic material of the dominant host cell population as a result of clonal evolution and/or clonal selection can hamper the correct identification of the origin of aberrant cells after allo-BMT, thus confounding the assessment of the chimeric state. Consequently, a good knowledge of the techniques applied in clinical practice and careful interpretation of their results are essential. A lack of host-specific markers at the time of clinical relapse is not adequate for verifying the presence of donor cell leukemia, and unequivocal demonstration of donor-specific markers is also required.