[Relevance of clonal hematopoiesis for cellular therapies]

The detection of clonal hematopoiesis (CH) in patients with hematologic neoplasms who are undergoing a cellular therapy is common. The most frequently used cellular therapy procedures include autologous and allogeneic hematopoietic stem cell transplantation (HSCT) and, more recently, chimeric antigen receptor (CAR) T‑cell therapy. All three procedures differ fundamentally in terms of harvesting and manufacturing aspects as well as usage of the respective cell product. Therefore, the importance of CH in relation to the respective treatment method must be evaluated and assessed differently. In autologous HSCT, the extent of previous cytotoxic therapy significantly contributes to the high prevalence of CH. The clinically most important aspect is the development of secondary neoplasms from a pre-existing CH clone and the potential risk for enhanced cardiovascular side effects. In allogeneic HSCT, the donor selection with respect to the age largely determines the probability for the presence of CH. In this setting, the development of secondary malignancies only plays a minor role compared to the autologous HSCT. In fact, the induction of a graft versus host (GvH) or a graft versus leukemia (GvL) effect and its influence on progression-free and overall survival seem to be of possible clinical relevance. The CAR T‑cell therapy is closely linked to inflammatory reactions regarding its mode of action and the associated side effects. In this context CH might be closely linked to the effectiveness and side effects of the CAR T‑cell therapy. Initial data reported a high prevalence of CH in patients before CAR T‑cell therapy and indicated an increased rate of inflammatory side effects, although no negative effect on survival has yet been demonstrated.