Late transplant‐associated thrombotic microangiopathy verified in bone marrow biopsy specimens is associated with chronic GVHD and viral infections

Abstract

AbstractObjectivesTo describe late transplant‐associated thrombotic microangiopathy (TA‐TMA) as chronic endothelial complication in bone marrow (BM) after allogeneic hematopoietic stem cell transplantation (HSCT).MethodsBM specimens along with conventional diagnostic parameters were assessed in 14 single‐institutional patients with late TA‐TMA (more than 100 days after HCST), including 11 late with history of early TA‐TMA, 10 with early TA‐TMA (within 100 days), and 12 non TA‐TMA patients. Three non‐HSCT patients served as control. The time points of BM biopsy were +1086, +798, +396, and +363 days after HSCT, respectively.ResultsLate TA‐TMA patients showed an increase of CD34+ and von Willebrand Factor (VWF)+ microvascular endothelial cells with atypical VWF+ conglomerates forming thickened VWF+ plaque sinus in the BM compared to patients without late TA‐TMA and non‐HSCT. Severe chronic (p = .002), steroid‐refractory GVHD (p = .007) and reactivation of HHV6 (p = .002), EBV (p = .003), and adenovirus (p = .005) were pronounced in late TA‐TMA. Overall and relapse‐free survival were shorter in late TA‐TMA than in patients without late TA‐TMA (5‐year OS and RFS: 78.6% vs. 90.2%, 71.4% vs. 86.4%, respectively).ConclusionChronic allo‐immune microangiopathy in BM associated with chronic, steroid‐refractory GVHD and/or viral infections are key findings of late, high‐risk TA‐TMA, which deserves clinical attention.