A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia
Status:
Completed
Trial end date:
2012-07-01
Target enrollment:
Participant gender:
Summary
Background:
- Severe aplastic anemia (SAA) can lead to problems with bone marrow health and result in
low blood cell counts, which require frequent transfusions. Standard initial treatment
for SAA involves injections of antithymocyte globulin (ATG) plus cyclosporine (CsA).
Patients with SAA who do not respond to initial treatment with ATG (refractory) have a
high risk of dying without additional treatment. In these cases, for those who do not
have a matched bone marrow transplant donor there is no well-defined standard therapy.
In our experience with patients who do not respond to horse ATG + CsA, only about
one-third of patients who are re-treated with rabbit ATG + CsA improve. Experience with
cyclophosphamide in the treatment of refractory severe aplastic anemia suggests that
this drug is able to improve blood counts in about 50% of cases. However, the
cyclophosphamide regimen has been associated with a significant infection risk (mostly
caused by fungus) in studies conducted over 10 years ago due to the lowering of the
white blood cell levels.
- Better antibiotic drugs against fungus have been developed and are widely used to treat
patients who have low white blood cell counts and are at risk of developing infections.
In SAA patients in particular, these newer antibiotics have had a large impact in
preventing and treating fungus infections. Researchers are revisiting the use of
cyclophosphamide at lower doses to minimize its side effects given in combination with
another immune suppressant, fludarabine.
Objectives:
- To determine the safety and effectiveness of the combination of fludarabine plus
cyclophosphamide in treating severe aplastic anemia that has not responded to initial
treatments.