3.1 Clinical data
A total of 209 pediatric patients underwent allo-HSCT, of which 20 were diagnosed with TA-TMA. This equates to 9.60% (95% CI = 5.5%–13.6%). The gender split was 11 males (55%) and 9 females (45%), with a median age of 146 (10–190) months. Basic clinical and demographic information for the 20 patients with TA-TMA is shown in Table 1. Primary diseases included aplastic anemia (30%), acute myeloid leukemia (20%), hemophagocytic lymphohistiocytosis (15%) acute lymphoblastic leukemia (5%), Fanconi anemia (5%), myelodysplastic syndrome (5%), mixed-phenotype acute leukemia (5%), mucopolysaccharidosis (5%), and myeloid sarcoma (5%). According to routine clinical practice in our center, haplo-identical donors were a common source of stem cells, with peripheral blood being the main source. The majority of recipients received busulfan (BU)-cyclophosphamide (CY) and anti-thymocyte globulin (ATG) therapy for myeloablative conditioning. Almost all transplant recipients received CNI-based GVHD prophylaxis, and only one case used sirolimus. Nineteen patients (95%) achieved neutrophil and platelet engraftment. The median neutrophil engraftment time was 15 (10–22) days and the median platelet engraftment time was 16 (7–39) days following allo-HSCT. The median count of graft mononuclear cells was 8.335 (0.821-39.6) × 108/kg and the CD34+ cell count was 7.95 (0.353–23.6) × 106/kg.
3.2 Clinical features of pediatric patients with TA-TMA
TA-TMA was diagnosed at a median of 94 days (7–289) post-HSCT. Eleven (55%) patients had early-onset TA-TMA, which happened within 100 days post-HSCT, while the remaining 9 (45%) patients had late-onset TA-TMA, which happened at >100 days post-HSCT. Early-onset TA-TMA occurred at a median of 56 (7–94) days, and late-onset TA-TMA occurred at a median of 157 (104–297) days. Nine cases were combined stage III-IV-GVHD, of which 6 were late-onset TA-TMA.
The most common symptom of TA-TMA was ecchymosis. Seventeen cases had varying degrees of bleeding, mainly in the skin and mucous membranes, with black-purple petechiae as a typical manifestation, while the gastrointestinal tract and urinary system were also involved. Case ”5” showed diffuse alveolar hemorrhage. Seven cases suffered from dyspnea, which was manifested as high-flow oxygen inhalation of 3 L/min and above mask oxygen inhalation, CAPA-assisted ventilation, and even mechanical ventilation with other advanced support, where transcutaneous oxygen saturation could be maintained at approximately 95%. Five cases had central nervous system symptoms, which manifested as convulsions and lethargy. The main clinical signs of TA-TMA were hypertension and effusion. The blood pressure of 18 cases was higher than the higher blood pressure values typically observed in children with hypertension of the same age. Furthermore, seven cases had serous cavity effusion, mainly manifesting as pleural effusion and pericardial effusion.
The median platelet counts, hemoglobin, and LDH levels were 21 (1–79) ×109/L, 79 (41–106)g/L, and 715 (350–4034) U/L, respectively. All 20 patients had a progressive decrease in platelets, of which 16 patients received transfusion that was ineffective. Proteinuria was positive in 16 cases and 2 patients showed ruptured red blood cells in peripheral blood smears. Fifteen patients were monitored for sC5b-9, of which 13 patients displayed higher levels than the normal range. Pathological examination was performed in 13 cases, and microthrombosis was evident in the microvascular pathological films of 7 of them.