Table 1.

Strategies for Relapse Prevention

Improved Preparative Therapy Incorporating new drugs with stronger anti-leukemia activity and/or less toxicity without compromising dose intensity Examples under investigation: monoclonal antibodies (radiolabeled or not), clofarabine, treosulfan

Graft Engineering Allograft enrichment with leukemia- or lineage-specific cytotoxic T lymphocytes Graft depletion of alloreactive T cells NK cell enrichment or adoptive transfer

Preemptive Treatment Monitoring for MRD (cytogenetics, PCR, flow cytometry, etc.) Intervention based on detection of MRD Therapeutic approaches: pharmacologic, immunologic, cellular therapies

Early Withdrawal of Immunosuppression High risk of GVHD may offset reduced relapse risk

Maintenance Relapse risk defined by pre-transplant parameters, e.g., advanced disease stage, presence of high-risk karyotype or genetic mutation, or detection of MRD before and/or after AlloSCT Therapeutic approaches: pharmacologic, immunomodulatory, cellular therapy Approaches under investigation (AML): azacitidine, FLT3 inhibitors

Ideal Maintenance Agent Documented activity against the disease Acceptable nonhematologic toxicity (will be tolerated early after transplant) Acceptable myelotoxicity (will not interfere with engraftment) Minimal drug interactions Will not inhibit GVT Will not worsen GVHD Caveats to Maintenance Strategies Dose is likely to be lower than in other scenarios (60, 61) Dose escalation trials are essential and randomized trials ultimately necessary given multiples confounding variables