This article is part of the July 2018 issue of ASBMT eNews. View the full issue in PDF format here.
Researchers Identify Genes Associated With Mortality After Matched Unrelated Donor Transplant
Researchers have performed the first exome-wide association study to identify genes that contribute to mortality after HLA-matched unrelated-donor transplantation. The study, published in Blood, included nearly 2,500 patients with acute myeloid leukemia, acute lymphoblastic leukemia or myelodysplastic syndrome and more than 2,200 patients with 10/10 HLA-matched donors. Researchers discovered that variant genotypes of OR51D1 in transplant recipients were associated with overall survival and transplant-related mortality, while donor genes ALPP, EMID1, SLC44A5, LRP1, HHAT, LYZL4 and NT5E were linked to overall survival, transplant-related mortality and disease-related mortality. Further studies may provide individualized risk prediction and prognosis, as well as alternative donor selection strategies, the researchers concluded. Read More
IL-1 Receptor Antagonist Treats Adverse Events Linked to CAR T-Cell Therapy
Anakinra treats cytokine-release syndrome (CRS) and neurotoxicity associated with chimeric antigen receptor-modified T (CAR T) cell therapy in mice with high leukemia burden, according to a study appearing in Nature Medicine. CAR T-cell therapy, used to treat leukemia in mice, resulted in high fever and increased IL-6 levels, which are characteristic of CRS. Researchers were able to prevent CRS by depleting monocytes or by blocking the IL-6 receptor using tocilizumab. However, tocilizumab failed to protect the mice from neurotoxicity. When the IL-1 receptor antagonist anakinra was tested, both CRS and neurotoxicity were eliminated, resulting in extended leukemia-free survival. Read More
Targeting Dual Antigens With CAR T-Cell Therapy
Using compound chimeric antigen receptor-modified (cCAR) therapy to target CD123 and CD33 on acute myeloid leukemia (AML) cells eliminates the disease and leukemic stem cells and has the potential to prevent relapse, reports a study published in the journal Leukemia. Researchers indicated that dual antigen targeting of AML would overcome the challenges of single-antigen therapy, such as antigen escape. Researchers used four leukemia mouse models to test the cCAR therapy, which resulted in superior in vivo survival compared to the control-treated group. Following treatment, mice received alemtuzumab to eliminate cCAR T cells from murine blood and tissues. The researchers concluded that single-antigen approaches may be insufficient and that targeting dual antigens simultaneously may be more effective. Read More