Transplant Cell Ther. 2024 Mar 21:S2666-6367(24)00292-6. doi: 10.1016/j.jtct.2024.03.019. Online ahead of print.
ABSTRACT
INTRODUCTION: Transplant-associated thrombotic microangiopathy (TA-TMA) is associated with high morbidity and mortality. Although with the introduction of eculizumab the survival has significantly improved, there is still a need for improvement, especially in high-risk patients.
OBJECTIVES: This study aims to describe the results obtained with eculizumab in a pediatric cohort with the attempt to define which risk factors could determine the response to treatment.
METHODS: We designed a national multicentre retrospective study, where children treated with eculizumab for high-risk TA-TMA were included.
RESULTS: Twenty-nine patients were included after a first (n=28) or a second allogeneic hematopoietic stem cell transplantation (HSCT) (n=1) for malignant (n=17) or non-malignant diseases (n=12). Median time from HSCT to TA-TMA diagnosis was 154 days (IQR 103-263). Eleven patients (38%) were initially diagnosed of low – intermediate risk TA-TMA and progressed to high-risk TA-TMA (hrTA-TMA), with a median time of 4 days (IQR 1 – 33). SC5b-9 was increased in 90% of 20 patients where measured. Renal (n=12), pulmonary (n=1) and intestinal (n=1) biopsy confirmed the diagnosis in 12/14 patients (85%). Seventeen patients (58%) presented extrarenal involvement with serositis (n=13, 44,8%), pulmonary (n=12, 41,4%), gastrointestinal (n=8, 27,6%), cardiovascular (n=7, 24,1%) or central nervous system (CNS) (n=2, 6,9%) involvement. Median time from hrTA-TMA diagnosis to the initiation of eculizumab was 7 days (IQR 1-18). Overall, 19 patients (65.5%) responded to eculizumab of whom 17 (58,6%) presented complete response and 2 (6.9%) achieved partial response. The remaining 10 patients (34.5%) did not present any type of response. The TA-TMA ORR was 27.59 % (95% CI 14.87 – 47.66), 55.17% (95% CI 38.43 – 73.48) and 62.07% (95% CI 45.10 – 79.13%) at 1, 3 and 6 months post eculizumab initiation, respectively. In the multivariate analysis the pulmonary involvement decreased the probability of response (HR 0.18, p-value 0.0298). The 1-year OS was 55.2% (95% CI: 35.6-71.0) for the whole cohort and 83.3% (95% CI: 56.7-94.3) for patients who responded to eculizumab. The presence of pulmonary (HR 14.93, p-value 0.0043) and CNS involvement (HR 8.63, p-value 0.0497) presented a statistically significant decrease in survival.
CONCLUSION: We found that patients diagnosed of hrTA-TMA with pulmonary involvement presented a poor response to eculizumab and patients with pulmonary and CNS involvement a significant decreased in survival. With these results, we hypothesize that using eculizumab at an early stage of the disease and before organ damage is established, the response and therefore the survival might significantly improve.
PMID:38521410 | DOI:10.1016/j.jtct.2024.03.019
