Background: Clonal hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. (CH) is a feature of severe 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… (SAA), but its clinical significance is debated.
Methods: We integrated longitudinal clinical and CH data from patients with SAA treated with immunosuppression plus 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: … (IST-EPAG) in a phase 2 trial to characterize clonal dynamics during recovery and progression to myeloid cancer or paroxysmal nocturnal hemoglobinuria paroxysmal nocturnal hemoglobinuria: (par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A… (PNH); CH was defined as the presence of somatic mutations at a variant allele frequency of 0.1% or greater.
Results: In total, 204 SAA patients treated with IST-EPAG were evaluated from disease onset to median follow-up of 5.5 years. CH was observed in 128 of 204 (63%) patients before treatment and in 131 of 180 (73%) after therapy who were evaluated at the 6-month timepoint and were not off-study. Patients mostly had CH in PIGA (N=53, 26%), DNMT3A (N=42, 21%), BCOR (N=35, 17%), and ASXL1 (N=25, 12%). There appeared to be two distinct patterns of malignant clonal evolution. Early evolutions, within 1 year from treatment, were primarily chromosome 7 aberrations and occurred in 11 (5%) patients. In another eight (4%) patients, late evolutions, 4-5 years after therapy, were initiated by early selection of ASXL1-mutated or U2AF1-mutated clones. Evolution to PNH, observed in 10 of 204 patients (5%), was associated with expansion of PIGA clones usually present before treatment.
Conclusions: Among patients with SAA treated with IST-EPAG, early and late patterns of clonal evolution to myeloid cancer were observed: Chromosome 7 abnormalities occurred within 1 year, whereas later events (4-5 years) involved stepwise 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. acquisition in preexisting ASXL1- or U2AF1-mutated clones