Starting in 2010, Dr. Bertaina developed an innovative approach of graft manipulation based on the physical elimination of αβ T cells and CD19+ B cells. The goal of this work was to broaden HSCT access and ensure the possibility of immediate transplantation to any patient in the need, especially those lacking a suitable donor because of their less represented ethnicity. By depleting haploidentical peripheral blood stem cells of αβ T-cells and CD19+ B-cells (αβ haplo-HSCT), Dr. Bertaina successfully transplanted over 500 pediatric patients and obtained 70% leukemia-free survival in children with acute leukemias and 90% disease-free survival in patients with non-malignant disorders. This pioneering work represents a major milestone in the field of T-cell depleted haploidentical HSCT and has ensured that hundreds of children without a matched donor can now be cured worldwide.
In hematological malignancies, the success of αβ haplo-HSCT lies, at least partially, in the presence of large numbers of γδ T cells. However, γδ T cells rapidly diminish after the transplant, reaching physiologic levels at about six months post αβ haplo-HSCT. Curiously, the timing of relapse for most αβ haplo-HSCT recipients correlates with the loss of γδ T cells suggesting γδ T cells confer a potent anti-leukemic effect. In her Lab, Dr. Bertaina explores strategies aimed at increasing the frequency and persistence of γδ T cells as a stand-alone treatment for pediatric acute myeloid leukemia. With this project, her long-term goal is to develop a cell-based product that can be safely infused into children with leukemia to improve outcomes. More broadly, this work lays the foundation for the use of third-party off-the shelf γδ T cells for a wide range of hematopoietic and solid malignancies.
Lastly, Dr. Bertaina has long focused on investigating causes of pediatric acute leukemia, in particular a rare and highly aggressive form of childhood leukemia, Juvenile Myelomonocytic Leukemia (JMML). In this disease, Dr. Bertaina demonstrated the down-regulation of miR-150-5p and its involvement in the pathogenesis through STAT5b and, subsequently, she performed whole genome sequencing on bone marrow‐derived CD34+ cells showing a broad genomic hypermethylation in samples of patients treated or not with a demethylating agent (5-Azacytidine), depicting a novel scenario of pathogenetic epigenetic regulation which remains currently poorly understood in JMML. On a clinical side, Dr. Bertaina works extensively with the EWOG-MDS and the JMML North American groups to establish new treatment protocols for this deadly malignancy. At Stanford, part of her lab is devoted to understanding the epigenetic mechanisms underlying the disease.