Description of Clinical Expertise

While HLA-matched related sibling donors are available for ~30%, they are more difficult to identify for older patients given that their siblings will also be older and often have medical comorbidities that exclude them from donating. In addition, older donor age may be associated with a greater risk of graft failure. As such, I have worked to expand the availability of allogeneic transplantation to older patients through HLA-haploidentical transplantation with post-transplant cyclophosphamide, which allows us to use children, grandchildren, nieces, and nephews as donors. Another former barrier to transplanting older patients was the intensity of conditioning. Historically allogeneic transplantation was limited to patients younger than 50 due to high treatment-related mortality associated with myeloablation. In my work, I demonstrated that utilizing nonmyeloablative HLA-haploidentical transplantation for patients in their 70’s and 60’s yielded similar outcomes to patients undergoing transplantation in their 50’s. In addition to an expertise in allogeneic transplantation, I specialize in the treatment of all phases of care for patients with acute lymphoblastic leukemia and myeloid diseases including acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, and chronic myeloid leukemia.

Description of Research Expertise

Allogeneic blood or marrow transplantation is the only potentially curative option for patients with relapsed, refractory, or high-risk hematologic malignancies. Unfortunately, only a third of patients have an available HLA-matched related donor. Partially HLA-mismatched related (HLA-haploidentical) transplantation allows identification of a donor for the vast majority of patients. In the past, HLA-haploidentical transplantation was associated with excessive nonrelapse mortality and poor overall survival. My research has contributed to the understanding of a novel technique that utilizes post-transplant cyclophosphamide as graft-versus-host disease prophylaxis after HLA-haploidentical transplantation. Using risk stratification with the disease risk index developed by Armand et al., I demonstrated that outcomes after nonmyeloablative HLA-haploidentical transplantation are comparable to that after reduced intensity HLA-matched transplantation. Similar to my work in older patients described above, I have also shown that nonmyeloablative HLA-haploidentical transplantation is safe and effective for pediatric and young adult patients. In addition, I have contributed to research examining early biomarkers, such as ST2, as predictors of nonrelapse mortality after HLA-haploidentical transplantation. Finally, to improve outcomes further, I have conducted research to examine the association of donor characteristics with transplantation outcomes. I showed that parent donors were associated with more graft failure when compared with sibling or offspring donors, but that survival was no different. Importantly, in that analysis, survival was affected by recipient age with recipients over 55 having inferior survival to younger patients. This work supports my proposed research agenda to evaluate the utility of the frailty phenotype tools to predict an older patient’s risk of nonrelapse mortality after induction chemotherapy and allogeneic transplantation as discussed in this proposal. Finally, my research has contributed to the widespread adoption of HLA-haploidentical transplantation with post-transplant cyclophosphamide, I have advanced the understanding of how we can improve its outcomes further, and I hope to continue to advance the field through studying frailty phenotype assessments in older patients with leukemia and myeloid malignancies undergoing induction then consolidative allogeneic transplantation.