Background: Immunosuppressive therapy Immunosuppressive therapy: Immunosuppressive drug therapy lowers your body's immune response. This prevents your immune system from attacking your bone marrow, allowing bone marrow stem cells to grow, which raises blood counts. For older patients with acquired aplastic anemia, immunosuppressive drug therapy is the… (IST) yields durable hematologic improvement (HI) in a subset of patients with lower-risk myelodysplastic syndrome (MDS). Age, human leukocyte antigen human leukocyte antigen: (LEW-kuh-site ANT-i-jun) One of a group of proteins found on the surface of white blood cells and other cells. These antigens differ from person to person. A human leukocyte antigen test is done before a stem cell transplant to closely match a donor and a recipient. Also called HLA. (HLA)-DR15 positivity, and duration of transfusion dependence are putative clinical variables predictive for response. We investigated the effect of somatic gene mutations on response to IST in lower-risk MDS.
Patients and methods: Forty of 66 patients who received antithymocyte globulin antithymocyte globulin: ATG is an immunosuppressant, a drug that lowers the body's immune response. It is typically used with cyclosporine as the first-line immunosuppressive therapy (IS) to treat patients with acquired aplastic anemia. In some cases it is used as a treatment for patients with MDS and PNH. with or without cyclosporine cyclosporine: Cyclosporine is used along with antithymocyte globulin (ATG), another immunosuppressant, for treating aplastic anemia and some other forms of bone marrow failure. A identified at the Moffitt Cancer Center were molecularly profiled using a 49-gene myeloid panel. All patients profiled received antithymocyte globulin, and cyclosporine A was provided to 60% of patients.
Results: The overall frequency of HI was 42%. Presence of a large granular lymphocytic clone clone: To make copies. Bone marrow stem cells clone themselves all the time. The cloned stem cells eventually become mature blood cells that leave the bone marrow and enter the bloodstream. , hypocellular hypocellular: A condition in which there are too few cells, for example, within the bone marrow. Patients with aplastic anemia have hypocellular bone marrow. bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. , HLA HLA: See human leukocyte antigen. -DR15 positivity, trisomy 8, and age had no influence on response to IST. Among 40 patients evaluated by next-generation sequencing, the presence of an SF3B1 mutation mutation: Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow. (MT) was significantly associated with IST nonresponse (1 of 9 SF3B1 MT, 11% vs. 21 of 31 wild type, 68%; P = .002). All patients with SF3B1 MT had ring sideroblasts > 15% (RS) by morphology morphology: The study of the structure and form of an organism or one of its parts. ; the corresponding HI rate was 20% among patients with RS versus 50% for those without RS (P = .09).
Conclusion: These findings support the clinical implementation of genomics in MDS. The presence of an SF3B1 mutation adversely influences response to IST and should be incorporated into treatment decisions upon validation of these findings.