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.