Transplant-associated thrombotic microangiopathy (TA-TMA) has a wide range of presentations after hematopoietic stem-cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA-TMA. Among the 1451 HSCT recipients, early TA-TMA occurred in 45 (3.1%) patients at a median of 27 (3-91) days, and late TA-TMA in 39 (2.7%) patients at a median of 303 (122-2595) days. Patients with early TA-TMA were more likely to have high blood calcineurin-inhibitor levels (P < .001) and acute graph-vs-host disease (GVHD, P < .001), while late TMA patients were more likely to have chronic GVHD (P < .001). The estimated median overall survival after onset of TMA for the entire cohort was 6 months. The estimated median overall survival was not reached in patients with an improvement of TMA vs 2 months in patients with no improvement (P < .001). In the early TMA group, older age (for every 10 years, HR 1.40; 95% CI 1.00-1.94; P = .049) and bacterial infection (HR 2.42; 95% CI 0.98-6.00; P = .056) were positively associated with mortality. Switching to MMF treatment (HR 0.40; 95% CI 0.16-0.99; P = .047) and improvement of TMA (HR 0.08; 95% CI 0.03-0.25; P < .001) were negatively associated with mortality in the multivariate analysis. In the late TMA group, the improvement of TMA was the only independent predictor associated with a lower risk of death (HR 0.05; 95% CI 0.02-0.19; P < .001). Mortality rates in both early and late TMA remain unacceptably high. Future studies are needed for early diagnosis, trigger identifications, and use of targeted treatments.
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http://dx.doi.org/10.1002/ajh.25922 | DOI Listing |
Bone Marrow Transplant
January 2025
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication in hematopoietic cell transplantation (HCT). Given the rarity of prospective pediatric studies on TA-TMA, this study aimed to evaluate the incidence, survival outcomes, and risk factors for predicting early the development of TA-TMA in a pediatric population following allogeneic HCT. We conducted a prospective analysis of 173 pediatric patients to evaluate the incidence, survival outcome, and risk factors of TA-TMA.
View Article and Find Full Text PDFTransplant Cell Ther
January 2025
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati, Cincinnati, OH.
Background: HSCT conditioning regimens cause massive lysis of hematopoietic cells with release of toxic intracellular molecules into the circulation.
Objectives: To describe the response to oxidative stress early after hemopoietic stem cell transplantation (HSCT) and assess the association of early oxidative stress with later transplant outcomes.
Study Design: Key components of in the body's physiological response to oxidative stress were studied in a cohort of 122 consecutive pediatric allogeneic HSCT recipients.
Clin Chim Acta
January 2025
Department of Laboratories, Seattle Children's Hospital, Seattle, WA, United States; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States. Electronic address:
Background: The complement membrane attack complex involves C5b-mediated assembly of C6-C9 polymers to form pores in cell membranes during complement activation. Inactive complexes can become soluble C5b-9 (sC5b-9) when they bind to Protein S. Elevated sC5b-9 levels are associated with increased risk of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA), a serious condition which can be improved with eculizumab therapy.
View Article and Find Full Text PDFPediatr Transplant
February 2025
Pediatric Hematology Oncology and Stem Cell Transplant, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Background: Veno-occlusive disease (VOD) and transplant-associated thrombotic microangiopathy (TA-TMA) remain a diagnostic and therapeutic challenge for patients undergoing hematopoietic stem cell transplant (HSCT). Both VOD and TA-TMA share an underlying etiology of microvascular endothelial damage. Potential under-recognition of TA-TMA in the context of VOD leaves HSCT recipients vulnerable to additional endothelial damage, and risk of end-organ failure.
View Article and Find Full Text PDFHematology Am Soc Hematol Educ Program
December 2024
Section of Hematology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic cell transplantation is characterized by microangiopathic hemolytic anemia (MAHA) with persistent schistocytosis, elevated markers of hemolysis, thrombocytopenia, and microvascular thrombosis leading to ischemic injuries in the kidneys and other organs. The initial evaluation of the disease requires confirmation of non-immune MAHA and careful examination of known secondary causes of TMA. Due to increased likelihood of long-term renal failure and overall mortality, a rapid diagnosis and treatment of the underlying trigger is needed.
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