Minimal residual disease in solid tumor malignancies: a review

The increase in the number of patients treated with high-dose chemotherapy/autologous stem cell transplantation (HDC/ASCT) for solid tumor malignancies has generated concern about the infusion of tumor cell contamination in the graft. In an effort to study so-called minimal residual disease (MRD) in the HDC/ASCT setting, a variety of assay methods have been used. Although these assays vary in terms of sensitivity and specificity of tumor detection, they are in agreement as to the presence and viability of tumor cells in ASCT grafts. A growing body of evidence indicates that MRD is present in ASCT grafts from neuroblastoma, breast cancer, and ovarian cancer patients. More importantly, several retrospective studies have determined that the infusion of tumor cells with the ASCT graft is strongly associated with post-ASCT relapse. Gene-marking studies have directly demonstrated that infused tumor cells are present at sites of disease relapse. Thus, the issue of tumor contamination of autologous grafts is an area of growing concern. This review article details the current status of MRD in solid tumor malignancies, with emphasis on assay methodology, clinical utility, and clinical relevance in transplantation medicine.