Early Sickle Mortality Prevention

Dr. Fitzhugh is exploring new avenues of hematopoietic stem cell (HSC) transplantation for sickle cell disease (SCD), while also studying the currently underexplored long-term health effects of curative therapy in patients with SCD.

Currently, HSC transplantation offers the only real cure for patients with SCD, though the transplantation procedure can only be applied to select people, and it carries its own set of health risks. One risk is that traditional stem cell transplants involve near total destruction of existing bone marrow, thus severely immunocompromising the transplant recipient. Dr. Fitzhugh and her team have been developing an alternative approach in which the donor and recipient stem cells coexist, potentially reducing the risk for serious infections or other immune complications. Dr. Fitzhugh has demonstrated the efficacy of this non-myeloablative procedure in both mice and human volunteers, and is currently participating in a long-term follow-up study in people to see if they remain free of SCD.

Dr. Fitzhugh is also conducting a half-matched protocol to increase the number of people eligible for HSC transplantation. The current procedure requires a fully HLA-matched sibling donor, and less than 20% of SCD patients would qualify. Through a half-matched protocol, any immediate genetic relative (parents, children, and siblings) would be able to donate stem cells, though the immune system barriers and potential complications are greater. Dr. Fitzhugh is currently examining the feasibility of this approach in a clinical pilot study.

Dr. Fitzhugh is interested in learning more about how different types of curative therapies including HLA-matched sibling HSCT, haploidentical HSCT, gene therapy, and gene editing impact the heart, lung, kidney, liver, and brain, organs that when damaged lead to substantial morbidity and early mortality in adults with SCD. She is also interested in identifying genetic risk factors of myeloid malignancy development after curative therapy for SCD. Through these joint avenues of research, Dr. Fitzhugh’s group is finding new avenues to help people with SCD live longer and healthier lives and to develop a personalized approach to curative therapy for SCD.