RESULTS
Between 2015 and 2018, of a total of 50 transplants performed, 30
included prophylaxis against IFIs with micafungin in an alternating
pattern according to the previously described protocol. The underlying
disease and patient characteristics are shown in Table 1. Fifty percent
(15/30) of the patients were male, and the remaining were female. The
median age at the start of prophylaxis was 5.82 (3.14-9.80) years, and
70.0% (21/30) of patients were under 8 years old. Regarding weight,
87.1% weighed <33 kg. The indication for HSCT was
hemoglobinopathies in 76.7% (23/30), acute leukemia in 20.0% (6/30)
and Fanconi anemia in 3.3% (1/30). The donor was a family member in all
cases an HLA-identical sibling in 93.3% (28/30) and an
HLA-haploidentical sibling in 6.7% (2/30) of cases. The source of the
transplant was bone marrow in 90.0% and apheresis in 10.0%.
In 80.0% of the patients, the alternating Monday-Wednesday-Friday
schedule was followed, with doses adjusted according to weight after
bone marrow engraftment. In the remaining 20.0%, treatment with azoles
(voriconazole or posaconazole) was initiated at discharge due to GVHD,
with a switch to alternating micafungin due to azole toxicity,
presenting as severe renal insufficiency and cutaneous symptoms. The
immunosuppressant treatments were primarily cyclosporine, mycophenolate
mofetil, tacrolimus and/or sirolimus.
The prophylaxis duration was 2.33 months (1.53 to 3.98). In our study,
40.0% (12/30) of the patients had acute GVHD, and 6.7% (2/30) had
chronic GVHD, which prolonged the duration of alternating prophylaxis.
No serious adverse effects of the use of micafungin were observed in any
of the patients. There was also no breakthrough IFI during alternating
prophylaxis.
Determinations of serum levels of micafungin were performed in 14
patients. In these patients, 100% of the levels exceeded the threshold
of 0.25 mg/L, regardless of age, weight, administered dose, albumin
levels, creatinine and the presence or absence of GVHD.
Compliance was adequate in all patients.
The statistical comparison tests did not show significant differences in
micafungin levels according to patient weight (considering different
cut-off points for weight (20, 25, 33 kg) (p = 0.819, p = 0.533, p =
0.825). There were also no significant differences in micafungin levels
found between patients who developed GVHD and those who did not (p =
0.28).
There was no significant correlation between age (cut-off point 8 years)
and serum micafungin levels (Z = -1.292, p = 0.196).
Likewise, when investigating whether albumin levels may explain
differences in the levels of micafungin determined over time, the
association was not significant (p = 0.841, p = 0.726, p = 0.870 p =
0.873, respectively). The same was true for creatinine levels, although
high levels of micafungin were found to coincide with renal failure
(Table 2). A 19-year-old patient had a micafungin level of 18.21,
creatinine of 3.23 mg/dL and a glomerular filtration rate (GFR)
estimated by cystatin of 32 mL/min/1.73 m2. A
7-year-old girl had a micafungin level of 12.50, a creatinine level of
1.03 mg/dL and GFR estimated by cystatin of 51 mL/min/1.73
m2. A 1-year-old girl had a micafungin level of 9.30,
a creatinine level of 0.54 mg/dL and a GFR estimated by cystatin of 53
mL/min/1.73 m2.