Background: A Phase 3 randomized trial compared 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… with or without eltrombopag eltrombopag: What are the possible side effects of eltrombopag (Promacta)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using eltrombopag and call your doctor at once if you have: … in untreated patients with aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… (AA) and showed that addition of eltrombopag increased the rate, rapidity, and durability of hematological response, without increasing transformation to myeloid malignancies. We sought to systematically investigate clonal hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. (CH) dynamics from patient samples from this trial.
Methods: Peripheral blood and bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. aspirates were collected at diagnosis (i.e., baseline) and at 6 and 24 months from patients with severe or very severe AA. Genetic testing for somatic mutations was performed using 31-gene "core" and 291-gene "extended" custom targeted panels and analyzed longitudinally.
Results: Samples were collected from patients at baseline (n=170) and 6 (n=150) and 24 months (n=103); 85 patients' samples were tested at all three timepoints. Somatic mutations were present in 30% of patients at baseline, 55.3% at 6 months and 79.6% at 24 months, with a mean number of mutations per patient of 0.4, 1.2, and 2.5, at baseline and 6 and 24 months, respectively.
Conclusions: CH was frequent in patients with AA and its prevalence appeared to be higher at posttherapy timepoints than at diagnosis. CH in AA may reflect the survival and expansion of selected residual hematopoietic stem/progenitor cells associated with immune-mediated damage. (Funded by Cancer Research UK, Bloodwise UK, and Novartis AG; ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).