Clinical implications of minimal residual disease monitoring for stem cell transplantation after reduced intensity and nonmyeloablative conditioning

Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for a variety of hematological malignancies; however, relapse and treatment-related toxicities are major obstacles to cure. Nonmyeloablative and reduced-intensity conditioning regimens were designed not to eradicate the malignancy completely, but rather to be immunosuppressive enough to allow engraftment, and to serve as a platform for additional cellular immunotherapy. Minimal residual disease (MRD) typically persists after SCT, and is gradually eliminated with different kinetics typical of each disease. Significant progress has been achieved with technologies for MRD assessment. Quantitative PCR tests are very sensitive in detecting tumor-associated transcripts, allowing serial monitoring. Threshold levels have been established for some malignancies, above which relapse is imminent. Persistent negative tests, a low level or a decreasing MRD level are consistent with continuous remission, whereas high-level MRD or increasing levels predict an incipient relapse. Patients at high risk of relapse are candidates for additional cellular or targeted therapy. Immunotherapy is more effective for MRD than at frank relapse. Timing and dosing of therapy are not yet well established and depend on aggressiveness of the disease, type of conditioning, level and kinetics of MRD.