Kinetics of DNases after hematopoietic stem cell transplant

Abstract

The entire hematopoietic system is rapidly lysed over 8 to 10 days during hematopoietic stem cell transplant (HSCT), releasing toxic intracellular molecules such as cell-free DNA (cfDNA) and proteins such as actin into the circulation. Neutrophil extracellular traps released at the time of engraftment also contribute to the cfDNA burden. Clearance of cfDNA is essential for limiting tissue toxicity. We measured levels of cfDNA, DNase I and DNase1L3 in 108 consecutive patients receiving allogeneic HSCT at baseline and on days 0, 7, 14, 30, and 100. cfDNA levels peak at day 14 and are higher in patients with endothelial injury. DNase I levels are depleted on day 7, recovering quickly by day 14, and remain above baseline at day 100. DNase1L3 levels decreased below baseline at day 0, reached a nadir by day 7, but recovered by day 30 remaining above baseline at day 100. Patients with a periengraftment oxygen requirement and those with transplant-associated thrombotic microangiopathy had higher DNase I levels than those without. DNase1L3 levels did not influence any HSCT outcomes. We analyzed DNase I activity using plasmid DNA degradation and showed decreased activity on days 0 and 7, in agreement with reduced protein levels. Further studies are needed to understand the dynamics of DNases in patients undergoing HSCT, to assess their potential role in HSCT toxicities.