Patients who have iron overload due to chronic blood transfusions and have developedheart failure or who are at high risk of heart failure because of the high levels of ironin their hearts, will be treated with deferiprone, an investigational drug, incombination with deferoxamine (Desferal). Some studies suggest that deferiprone may bebetter than deferoxamine in removing iron from the heart and improving heart function,and that using both drugs together may remove more iron. Participants would make a clinicvisit for lab studies each week, and would continue to take deferiprone for as long astheir physician feels it is useful in their care.
Repeated red cell transfusions lead to transfusional iron overload because the body lacks
an efficient mechanism to excrete excess iron. Without treatment, iron accumulates in the
liver, heart and endocrine glands. Cardiac complications including arrhythmias and
congestive heart failure are the most common cause of death from transfusional iron
overload. New magnetic resonance imaging (MRI) T2* techniques enable an estimation of
cardiac iron loading, and allow patients at the highest risk of cardiac disease (those
with T2* < 10 ms) to be identified. For over 30 years, deferoxamine has been the standard
therapy. However, the mode of administration is cumbersome (subcutaneous or intravenous
infusion over 8 to 12 hours daily), leading to poor compliance. Thus, cardiac disease and
early mortality continue to be a significant problem in patients treated with chronic
transfusions. Treatment of cardiac complications involves intensifying therapy with
deferoxamine, including recommending intravenous administration over a period of 24 hours
daily. Deferiprone is an oral chelating agent, not FDA approved for use in the United
States. Recent studies indicate that deferiprone is superior to deferoxamine in removing
cardiac iron and reducing iron-induced cardiotoxicity. The most serious side effect of
deferiprone is agranulocytosis, and other side effects are gastrointestinal symptoms,
reversible arthralgia, reddish discoloration of urine and rare cases of autoimmune
disease. Patients on the study will be closely monitored for these toxicities. Patients
who are currently regularly followed at The Children's Hospital of Philadelphia will be
prescribed deferiprone at 75 mg/kg/day in three divided doses, taken orally, in
combination with deferoxamine, at the patient's current dose. Labs will be drawn once per
week to monitor neutrophil count, with additional labs every three months to monitor
ferritin and ALT levels.
Drug: deferiprone
oral administration of 75 mg/kg/day in three divided doses, usually in combination with
deferoxamine therapy
Other Name: Ferriprox
Inclusion Criteria:
- Transfusional iron overload
- Overt cardiac failure or significant arrhythmia, OR high risk of developing cardiac
failure as determined by T2* < 10 ms by magnetic resonance imaging (MRI)
- Signed consent form
- Patient regularly followed at The Children's Hospital of Philadelphia
- Unwillingness to participate in, or lack of suitability for, a clinical trial
providing similar therapy
Exclusion Criteria:
- Previously treated with deferiprone and had severe adverse reactions necessitating
discontinuation
- Receiving other investigational drugs
- Receiving other drugs known to cause neutropenia
- Unexplained occurrences of neutropenia in past two years
- Pregnant or breastfeeding; or want to become pregnant.
- Sexually active but unwilling to use reliable birth control
- Other conditions which, in the opinion of the investigator, would make patient
unsuitable for enrollment
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Alan R Cohen, MD, Principal Investigator
Children's Hospital of Philadelphia