BMT Core - Oregon Health and Science University (OHSU) Consortium

PROJECT SUMMARY Allogeneic hematopoietic cell transplantation (HCT) is an essential therapeutic procedure used to enhance the outcome of patients with acute myeloid leukemia (AML). Recent advances in alternative donor transplantation and supportive care have allowed for a greater number of older adults and those with co-morbidities to pursue potentially curative transplant procedures. In addition, the emerging era of targeted therapy allows for the development of novel disease remission induction regimens as well as transplant conditioning regimens that can enhance outcomes. However, relapse after allogeneic HCT remains a major barrier to successful outcomes, with recent data suggesting that up to 50% of allogeneic HCT failure and mortality relate to persistence or relapse of underlying disease. Recent advances in the detection of minimal/measurable residual disease (MRD) have enhanced the capacity of identifying some patients at high risk of relapse after HCT. Using information obtained by cytogenetics, fluorescence in situ hybridization (FISH) and genomics, successful outcomes can still be achieved in a subset of myeloid malignancy patients transplanted in the setting of morphologically active or MRD-detectable disease at the time of transplant. Recent observations have demonstrated that more intensive remission induction chemotherapy followed directly by allogeneic transplantation can provide successful outcomes for patients with poorly responsive, unfavorable AML after primary induction treatment. This proposal will investigate the benefit of such aggressive intensive induction followed by immediate transplantation with myeloablative conditioning for patients with intermediate and high risk AML, when compared to current standard approaches. This effort will determine whether augmented remission induction therapy with early transplantation using sensitive MRD assessment before and after transplant for myeloid malignancies can be used to improve HCT outcomes with the most efficient health resource utilization. In so doing we hope to establish the importance of more intensive induction chemotherapy in creating opportunities for the best long-term transplant outcomes for the AML patient. Sensitivity of novel MRD assessments will be available for study that could determine the need for novel interventions for post-HCT patient management using a variety of emerging cellular and/or pharmacologic-targeted approaches.