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Hill, Wolfgang; Sotlar, Karl; Hautmann, Anke; Kolb, Hans‐Jochem; Ullmann, Johanna; Hausmann, Andreas; Schmidt, Michael; Tischer, Johanna; Pham, Thu‐Trang; Rank, Andreas und Hoechstetter, Manuela A. ORCID logoORCID: https://orcid.org/0000-0002-3526-9523 (2024): Late transplant‐associated thrombotic microangiopathy verified in bone marrow biopsy specimens is associated with chronic GVHD and viral infections. In: European Journal of Haematology [PDF, 1MB]

Abstract

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

Methods 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.

Results 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).

Conclusion 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.

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