Table 4 Therapies with curative intent
From: Advances in the diagnosis and treatment of sickle cell disease
Allogeneic hematopoietic stem cell transplant | |
HLA-matched sibling donor | Standard approaches rely on myeloablative conditioning with overall and disease-free survival rates in the 90% range for children and young adults with SCD Reduced intensity and reduced toxicity, nonmyeloablative regimens offer alternative strategies to achieve stable, mixed chimerism in adults with SCD |
Umbilical cord donor | Cord units from related or unrelated donors represent alternative sources of hematopoietic stem cells for children with SCD; routine use is limited by lower total cell dose Units from unrelated donors are associated with higher risk of graft rejection and graft-versus-host disease |
HLA-matched unrelated donor | Demographics of current donor pool limit this option for Black patients with SCD High rates of acute and chronic graft-versus-host disease remain a significant challenge |
Haploidentical donor | Haploidentical donors offer most accessible donor type for children and adults with SCD Strategies focused on T-cell depletion using post-transplant cyclophosphamide have improved engraftment rates and reduced graft-versus-host disease |
Autologous gene-based therapy | |
Gene addition or transfer | Lentiviral-based vector encodes modified β- or γ-globin transgenes to increase anti-sickling hemoglobin production Lentiviral-based vector transfers short-hairpin RNA (shRNA) targeting BCL11A to increase γ-globin expression Transduction efficiency is high with current vectors Concerns remain about risk of insertional oncogenesis and long-term high-level expression |
Gene editing | Genome editing focuses on correction of SCD mutation, downregulation of BCL11A or mimicking of hereditary persistence of fetal hemoglobin (HPFH) mutations Strategies rely on CRISPR-Cas9 technology or engineered DNA-cleaving enzymes such as zinc-finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs) |