1.
Prospective clinical and biomarker validation of the ASTCT consensus definition for transplant-associated thrombotic microangiopathy (TA-TMA)
Ma, S., Bhar, S., Guffey, D., Kim, R. B., Jamil, M., Amos, C. I., Lee, S. J., Hingorani, S. R., Sartain, S. E., Li, A.
Transplantation and cellular therapy. 2023
Abstract
INTRODUCTION Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications post-allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging due to non-standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study and to compare the impact and outcomes of employing the current clinical TMA definition (cTMA) versus the new consensus definition. METHODS We included patients aged 0 to 18 years who underwent their first allo-HCT from May 2021 to January 2023 at Texas Children's Hospital. We compared the incidence, biomarkers, and outcomes of TA-TMA applying the previous and recently proposed screening algorithms and definitions. RESULTS While the classic microangiopathic hemolytic anemia (MAHA)-based cTMA definition led to an incidence of 12.7%, the ASTCT-HR definition doubled the incidence to 28.5% by day 100. In contrast to patients with concordant diagnosis (+/+) who had significantly worse post-transplant survival, those reclassified as TA-TMA by the new definition only (-/+) had significantly different prognosis (100% survival at day 100) despite the lack of TMA-directed therapy. Furthermore, biomarkers of the terminal and alternative complement pathways (sC5b9 and Ba, respectively) were significantly elevated around day 15 in the concordant group (+/+) but not in the discordant group (-/+) when compared to the non-TMA patients. CONCLUSIONS The recently proposed ASTCT consensus TA-TMA diagnosis is more sensitive and allows earlier recognition of manifestation that requires closer clinical monitoring but risks over-diagnosis and over-treatment. We recommend additional prospective validation.
2.
Validation of treatment outcomes according to revised severity criteria from European Society for Blood and Marrow Transplantation (EBMT) for sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD)
Yoon, J. H., Yoo, K. H., Sung, K. W., Jung, C. W., Kim, J. S., Hahn, S. M., Kang, H. J., Lee, J. H., Im, H. J., Ahn, J. S., et al
Bone marrow transplantation. 2019
Abstract
Traditional severity criteria of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) were determined retrospectively but found inappropriate for therapeutic decisions. Data of 203 patients with SOS/VOD were collected according to the modified Seattle diagnostic criteria and were analyzed for validation of the revised severity criteria recently proposed from European Society for Blood and Marrow Transplantation (EBMT). According to the traditional severity criteria, none of the patients were mild grade, while 63.1% were moderate and 36.9% were severe grade. However, according to the revised EBMT criteria, the majority of patients (63.1%) were very severe, 18.2% were severe, 12.8% were moderate, and 5.9% were mild grade. The 100-day overall survival (OS) of mild, moderate, severe and very severe groups was 83.3, 84.3, 94.6, and 58.6%, respectively. Very severe SOS/VOD showed a significantly lower OS than the others (58.6 vs. 89.3%, p < 0.0001). The 100-day transplantation-related mortality was 25.2% in the entire cohort; 8.3% in mild, 8.0% in moderate, 2.7% in severe, and 36.7% in very severe SOS/VOD (p < 0.0001). The very severe grade newly classified by the revised EBMT criteria accounted for the majority of SOS/VOD associated with worse 100-day OS. Therefore, intervention should be applied at the latest for moderate to severe SOS/VOD before deterioration.