Diagnostik bei unklaren Zytopenien – wie und wann suchen wir nach klonaler Hämatopoese?

Abstract

Many studies have analyzed the clinical significance of clonal hematopoiesis. The collected data lead to the conclusion that in defined clinical constellations atargeted diagnostic search for clonal hematopoiesis seems reasonable. Adiagnostic algorithm and the selection of the right methods are required for use in everyday clinical practice. A search was carried out in PubMed for relevant literature using the terms clonal hematopoiesis, CHIP, and CCUS, which was evaluated and augmented with expert knowledge. Clonal hematopoiesis is defined as the presence of clonality in hematopoietic cells and is detectable in 5-95% of the aged population depending on the method used. Clinical relevance was demonstrated for larger clones with mutations in specific genes and subsequently the terms clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS) were introduced. For both constellations the relevant gene spectrum as well as the relevant clone size were clearly defined. In CHIP anormal blood count and differential blood count are present by definition. CHIP is therefore currently an incidental finding. In CCUS, on the other hand, cytopenia is present. The clinical risks of the two constellations differ. CHIP is associated with avery low risk of progression to a hematologic neoplasm, whereas in CCUS the risk is significantly increased depending on clone size, number and spectrum of mutated genes. Screening for CHIP is currently not useful. In the presence of persistent cytopenia of unclear cause targeted diagnostic tests including bone marrow evaluation and genetic analyses should be performed.