TY - JOUR
T1 - Late transplant-associated thrombotic microangiopathy verified in bone marrow biopsy specimens is associated with chronic GVHD and viral infections
AU - Hill, Wolfgang
AU - Sotlar, Karl
AU - Hautmann, Anke
AU - Kolb, Hans Jochem
AU - Ullmann, Johanna
AU - Hausmann, Andreas
AU - Schmidt, Michael
AU - Tischer, Johanna
AU - Pham, Thu Trang
AU - Rank, Andreas
AU - Hoechstetter, Manuela A.
N1 - Publisher Copyright:
© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
PY - 2024/5
Y1 - 2024/5
N2 - 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.
AB - 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.
KW - alloimmune microangiopathy
KW - atypical VWF+ conglomerates forming thickened VWF+ plaque sinus
KW - bone marrow specimens
KW - late transplant-associated thrombotic microangiopathy
KW - von Willebrand factor (VWF)+ microvascular endothelial cells
UR - http://www.scopus.com/inward/record.url?scp=85182827472&partnerID=8YFLogxK
U2 - 10.1111/ejh.14174
DO - 10.1111/ejh.14174
M3 - Article
C2 - 38243840
AN - SCOPUS:85182827472
SN - 0902-4441
VL - 112
SP - 819
EP - 831
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 5
ER -