Treatment of Refractory ITP Patients
First Line Therapy of Refractory ITP.
**Please note! The treatment approach described here is based on the author's experience and biases; other physicians who approach the treatment of refractory ITP differently may not be incorrect. The drug doses listed in some of the sections represent those commonly prescribed. However, drug doses in individual patients may differ from those listed here and depend on the patient's clinical situation and the doctor's preferences. Decisions on the treatment of individual patients with ITP are the sole responsibility of the treating physician.
Patients unable to maintain a safe platelet count (greater than 25-30,000) after splenectomy should receive additional treatment. In general, treatments with the fewest side effects are used first. Your physician may not use these treatments in the order listed because of personal preference or potential side effects.
Corticosteroids.
Most physicians try prednisone again in patients unresponsive to splenectomy.
Dose. The starting dose is usually 50-100 mg/day depending on the patient's weight. This is usually continued for 4-6 weeks. If a normal platelet count is attained, the dose is gradually tapered over several weeks. If the platelet count can be maintained at safe levels with doses of prednisone of 10 mg/day or less, this is probably the safest treatment and should be continued. If higher doses are required, other treatment is advised. Prednisone may also be given in combination with some of the other treatments that will be described later. Once a response is seen with the combination, the prednisone is tapered and, if possible, discontinued.
Side effects. These include gradual swelling of the face, neck and shoulders; fluid retention; gastric hyperacidity (heartburn); anxiety, difficulty sleeping and potassium loss. Osteoporosis (thinning of the bones) and an increased risk of infection may be problems if treatment is given over several months. Since hyperacidity is common, antacids or acid inhibitors may be indicated. The serum potassium should be monitored.
Rituximab (Rituxan)
B lymphocytes are involved in antibody production. This 'humanized' monoclonal antibody binds to and destroys B lymphocytes and interferes with autoantibody production. Rituximab has been used extensively in the treatment of a wide variety of other disorders so there is a large clinical experience concerning side effects.
Dose. Rituximab is given intravenously at a dose of 375 mg/M2 every week for 4 courses.
Results. Multiple studies have been reported with the following general conclusions: (1) approximately 50-60% of ITP patients will obtain a reimission due to rituximab but a substantial number of these will relapse over time; (2) a recent study (Patel et al. Blood 108:145a, 2006 abstract 479) reported that, of the adult ITP patients they treated with rituximab, slightly more that 50% attained a remission. However, only 1 out of 6 patients who were treated had a long-term remission (more than 2.5 years), although their data also suggested that further relapses after 2.5 years were unlikely. In summary, about 17% of ITP patients who are treated with rituximab can expect a long-term remission and, hopefully a cure.
Side effects. Symptoms during the infusion occur commonly; these are most severe during the first infusion. Symptoms may include: fever, chills, wheezing, hives, generalized swelling or a temporary fall in blood pressure. More severe side effects, including death, have been described, when rituximab is given for other diseases, but these have not been seen in ITP.
Danazol.
About 50% of patients who are treated will respond to danazol although responses may be slow (average response time of 2.7 months with 85% of responses occurring within 4 months).
Dose. One capsule (200 mg) 3 or 4 times daily for a minimum of 4 months and preferably for at least 10 months. Prednisone (50-100 mg/day) should be given at the same time. If a response occurs, prednisone should be tapered to very low doses and, if possible, stopped. If danazol treatment is successful, therapy should be given for at least one year and then gradually tapered. Responses are more likely in women who are more than 65 years old, in patients who responded to corticosteroids and in patients who have undergone splenectomy. Patients may require long-term treatment with danazol (sometimes with small doses of prednisone) to maintain a response.
Side effects. Danazol is a modified male hormone and may cause masculinizing side effects including weight gain, seborrhea (oily skin), acne, lowering of the voice and increased facial hair. Headache, fluid retention, lethargy, stomach upset and liver toxicity are less common. Liver function tests should be monitored monthly and the drug stopped if the tests become significantly abnormal.
Dapsone.
Since only a small number of patients have been treated with this drug, the response rate is not known. Responses persist for several months but relapse usually occurs unless therapy is continued. Dapsone should be considered as a substitute in patients whose platelet counts can be maintained with small doses of prednisone. Dapsone should be added to the prednisone and then, after a few weeks, the prednisone should be slowly tapered.
Dose. The dose is 75 mg-100 mg per day.
Side effects. This drug causes destruction of red blood cells at higher doses and this may result in anemia. In patients whose red blood cells have reduced amounts of the enzyme glucose-6-phosphate dehydrogenase, red cell destruction and anemia can be severe. Patients should be tested for this enzyme prior to using dapsone.
Colchicine.
This drug has been used only on occasion in ITP but is an extremely safe drug which has been used in the treatment of gout for many years. About 25% of ITP patients will respond. Responses occur during the first 3 months; drug withdrawal usually results in relapse. Like dapsone, colchicine should be considered as a substitute in patients whose platelet counts can be maintained with small doses of prednisone. Colchicine should be added to the prednisone and then, after a few weeks, the prednisone should be slowly tapered.
Dose. The starting dose is 0.6 mg daily. The dose is gradually increased to 0.6 mg three or four times daily if possible. In responding patients, the dose should be tapered to the lowest dose resulting in safe platelet counts.
Side effects. The only major side effect is diarrhea, which may be severe and often limits the dose.
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