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

• Published in: European journal of haematology Vol. 112; no. 5; pp. 819 - 831
• Main Authors: Hill, Wolfgang, Sotlar, Karl, Hautmann, Anke, Kolb, Hans-Jochem, Ullmann, Johanna, Hausmann, Andreas, Schmidt, Michael, Tischer, Johanna, Pham, Thu-Trang, Rank, Andreas, Hoechstetter, Manuela A
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.05.2024
• Subjects: Biopsy; Bone marrow; Bone marrow transplantation; CD34 antigen; Endothelial cells; Graft-versus-host reaction; Hematopoietic stem cells; Microvasculature; Stem cell transplantation; Steroids; Thrombotic microangiopathy; Transplants & implants; Viral infections; Von Willebrand factor; atypical VWF+ conglomerates forming thickened VWF+ plaque sinus; bone marrow specimens; von Willebrand factor (VWF)+ microvascular endothelial cells; late transplant‐associated thrombotic microangiopathy; alloimmune microangiopathy
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.14174

To describe late transplant-associated thrombotic microangiopathy (TA-TMA) as chronic endothelial complication in bone marrow (BM) after allogeneic hematopoietic stem cell transplantation (HSCT). BM 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. Late 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). Chronic 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.