Treatment of Refractory ITP Patients
Second 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.
These treatments are effective in many patients with unresponsive chronic ITP but they are not generally used unless patients do not respond to agents with less severe side effects (see first line treatment).
Standard Dose Chemotherapy.
The two drugs most commonly used are cyclophosphamide or azathioprine. Response rates to these two drugs are similar: about 50% of patients will obtain safe platelet counts on treatment and about one-third will attain a complete, unmaintained remission (cure). Your doctor may recommend either drug.
Cyclophosphamide (Cytoxan).
Dose. The starting dose is usually 150 mg per day. The dose is adjusted to cause mild lowering of the white blood count. Responses occur within 6-8 weeks. If a normal platelet count is attained, the drug is given at full dosage for 2 to 3 more months and then stopped.
Side effects. This drug may cause anemia or lowering of the white blood count (which if too severe may increase the risk of infection). The breakdown products of this drug are eliminated in the urine, and if they remain in the bladder for long intervals, they may cause irritation and bleeding. This may be prevented by drinking at least 2 quarts of fluids daily. Other side effects include liver toxicity and sterility (damage to sperm or eggs which prevent individuals from having children). Although rare, there is a risk of drug-induced secondary malignancies (e.g., acute leukemia), particularly if the drug is given for many months.
Azathioprine (Imuran)
Dose. The starting dose is usually 150 mg per day; the dose is adjusted to cause mild lowering of the white blood cell count. Response to this drug is often slow and sometimes requires treatment for 4-6 months before benefit occurs. If a normal platelet count is attained, the drug should be continued for at least a year and then tapered and stopped.
Side effects. This drug may cause anemia or lowering of the white blood count (which if severe may increase the risk of infection). Occasional patients note a loss of appetite or nausea. Although rare, the risk of secondary malignancies (e.g., acute leukemia or lymphoma) must be considered, particularly if the drug is given for many months.
Immunosuppressive Therapy
Mycophenolate-Mofetil (Cellcept).
This agent affects T and B lymphocyte function and is used as an immunosuppressant to prevent graft rejection after liver or kidney transplants.
Results. Only two small studies have been reported and one of these only as an abstract (Howard et al: Br J Haematol 117:712, 2002; Fibich et al: Bood 92:177a, 1998). In the first study, 15 ITP patients (9 had failed splenectomy) were studied. Of these, 2 attained normal platelet counts and 7 platelet counts above 50,000 on continued therapy. Response durations ranged from 1-17+ months. In the second study, 8 patients with 'Evan's syndrome' (a combination of ITP and autoimmune hemolytic anemia) were treated. Of these, 5 patients had a complete response (normal platelet count) and one a partial response (platelet count >50,000). Response durations ranged from 9 to 39+ months. A larger study with long-term followup will be required to evaluate the role of this drug in ITP.
Dose. The initial dose is 250 mg twice daily, which after 2 weeks is increased to 500 mg twice daily and after 2 more weeks is increased to 1000 mg twice daily.
Side effects. The drug is well tolerated, with headache being the most common side effect.
Cyclosporine.
Cyclosporine is a drug which suppresses the immune system and is commonly used in transplantation patients to prevent organ rejection or graft versus host disease. Because of its side effects and the limited experience with its use in ITP, it should be reserved for patients who do not respond to cyclophosphamide, azathioprine or mycophenolate-mofetil. Only two small studies have been published (Kappers-Klunne et al: Br J Haematol 114:121, 2001 and Emilia et al: Blood 99:1482, 2002). They treated 18 refractory ITP patients. Of these, 4 patients attained normal platelet counts and 5 patients, platelet counts >40,000 which persisted for 6-48 months after stopping treatment. Three other patients maintained normal platelet counts but required continued therapy. These results must be confirmed by a larger study.
Dose. The starting dose is 2.5 mg/kg of body weight given twice daily. Blood tests to measure drug levels, kidney function and liver function must be monitored carefully and doses adjusted as needed.
Side effects. The drug may cause kidney damage which may be severe and persistent. Other side effects include liver dysfunction, increased facial hair, tremor, high blood pressure and gum swelling. Secondary malignancy (e.g., lymphoma) has been described in the transplant setting.
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