Download (mg/kg/d) Serum Ferritin (ng/mL)

Rash and Low T2* MRI in a
Paediatric Thalassaemia
Patient
1
Patient Presentation
• 9 1/2-year-old male patient with
-thalassaemia
• Patient has been transfused with 1 unit every
3 weeks (0.46 mg/kg/d) since age 1 year
• At age 3 years, the patient began receiving
desferrioxamine and is currently receiving
desferrioxamine 40 mg/kg/d
– Usually doses > 40 mg/kg/d are not recommended
in paediatric patients
2
Thresholds for Parameters Used to
Evaluate Iron Overload
Parameter
Normal
LIC (mg Fe/g dw)
<1.2
Serum ferritin (ng/mL)
<300
Transferrin saturation (%)
20–50
Iron Overloaded State
Mild
3–7
Moderate
Severe
>7
>15
>1000 to <2500
>2500
>50
T2* (ms)
>20
14–20
8–14
Alanine aminotransferase (U/L)
<250
>250
Labile plasma iron (μM)
0–0.4
>0.4
<8
Increased risk of complications
Increased risk of cardiac disease
3
Courtesy of A. Taher, MD.
Response to Desferrioxamine
Baseline Results
Parameter
Value
Serum ferritin
3940 ng/mL
LIC
16.7 mg/g dry weight
T2*
10.6 msa
aIndicating
cardiac iron prevalence
4
Question
What should the next step be?
A. Continue on desferrioxamine at
current dose
B. Increase dose of desferrioxamine to
>50 mg/kg/d
C. Switch to deferiprone 100 mg/kg/d
D. Switch to deferasirox 30 mg/kg/d
5
Choice of Chelator
• Patient is already on a high dose of
desferrioxamine and a higher dose at his age
is contraindicated
• Although deferiprone is approved for patients
with thalassaemia when desferrioxamine is
inadequate, starting dose is 75 mg/kg/d and
doses >100 mg/kg/d are not recommended;
TID dosing may pose difficulties for a patient
his age
• Usual starting dose of deferasirox is
20 mg/kg/d, but 10 mg and 30 mg may also
be used; once-daily oral administration
makes deferasirox attractive for use in
6
children
Deferasirox Dosing
• Recommended starting dose and
modifications to treatment with deferasirox
are the same in children and adults
– In clinical studies, 20 or 30 mg/kg/d resulted in overall
maintenance or reduction of liver iron concentration,
respectivelya
– Starting dose of 10 mg/kg/d was not sufficient to achieve a
negative iron balance in heavily transfused patients
• Patient began treatment with deferasirox
30 mg/kg/d
aStudy
107
Cappellini MD, et al. Blood. 2006;107:3455-3462.
7
Question
At 1 month, patient developed a
moderate-to-severe skin rash. How
should this rash be managed?
A. Reduce dose, then gradually increase
dose to prior level when rash resolves
B. Interrupt drug, then reintroduce at lower
level when rash resolves, gradually
escalating to target level
C. Switch back to desferrioxamine or consider
deferiprone
8
Resolution of Rash
• Drug treatment interrupted due to moderateto-severe skin rash
• After 1 week, patient was restarted on
reduced drug dose (20 mg/kg/d) and rash
resolved
• After 2 months, dose was successfully
increased to 30 mg/kg/d
– Minor dose adjustments were made periodically
over the next 3 years in response to serum ferritin
levels
9
Skin Rash Treatment Algorithm
• Mild-to-moderate rash can be managed
without treatment interruption
• More serious rash necessitates treatment
interruption. Deferasirox should be
reintroduced at a lower dosage after rash has
resolved, with gradual dose escalation
• With severe rash, deferasirox should be
interrupted, then reintroduced at a lower
dose, possibly in combination with an oral
steroid, after rash has resolved. Deferasirox
dosage can then be gradually increased.
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Response to Treatment
• Serum ferritin levels decreased steadily over
next 3 years to <500 ng/mL
• Liver iron concentration decreased to
5.0 mg/g dry weight
• T2* readings increased steadily, from 10.6 ms
to 17.0 ms
• Patient then received a successful bone
marrow transplant
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40
Serum ferritin levels during treatment with deferasirox
4500
Serum Ferritin (ng/mL)
Deferasirox Dose (mg/kg/d)
Dose Adjustments
and Serum Ferritin Levels
4000
35
3500
30
3000
25
2500
20
2000
15
1500
10
1000
5
500
0
0
1
4
7
10
13
Month
17
23
26
29
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Conclusions
• Deferasirox at appropriate doses results in
continued reduction in serum ferritin levels
• Reduced cardiac iron burden in children, as
measured by increased T2*, is also achieved
with appropriate doses of deferasirox
• Skin rashes can be managed effectively, in
many cases without interruption of treatment
– In this patient, dose reduction to 20 mg/kg/d was sufficient
for resolution of rash
– Dose was then increased again to previous 30 mg/kg/d and
serum ferritin levels fell continuously for the next 3 years
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