Treatment of idiopathic thrombocytopenic purpura (ITP) in patients with refractoriness to or with contraindication for corticosteroids and/or splenectomy with immunosuppressive therapy and danazol.

BACKGROUND

The best treatment for patients with idiopathic thrombocytopenic purpura (ITP) who are refractory to or have contraindications for splenectomy and corticosteroid remains uncertain. We report here our experience with vinca alkaloids (VA), azathioprine (Azp) and danazol in 33 such patients (6 M/27 F), median age 66 (23-83).

METHODS

Group A (n = 19), Group B (n = 11), Group C (n = 17) patients were treated with VA, Azp and danazol. Fourteen patients were given more than one immunosuppressor agent. Sixteen patients were given 2 mg/week bolus infusions of vincristine (Vcr), while weekly slow infusions of vinblastine (Vnb, 0.1 mg/kg), for 2-4 weeks, were administered to the remaining 3 cases of Group A. Azp was administered at a daily dose of 150 mg for a median duration of 6 months. Danazol was administered at a median daily dose of 400 mg (400-800 mg), for a median length of 5 months. Response was defined as any increase of platelet count to higher than 30 x 10(9)/l, when platelet count was < 20 x 10(9)/l or any doubling of the basal platelet count otherwise. Remission, any increase of platelet count to higher than 100 x 10(9)/l lasting for 3 months or longer without therapy.

CONCLUSIONS

In Group A, there was a response rate of 63%, with 2 remissions (10%). All responses were observed after the first infusion. Two additional patients, who responded transitorily to VA, went into spontaneous remission 19 and 51 months after the last infusion of VA. In Group B, the response rate was 45%, with 1 remission (9%). The response was never observed before one month. One additional patient went into spontaneous remission 60 months after stopping Azp. In Group C, the response rate was 56% with 2 remissions (12%); 2 patients relapsed while on therapy, 4 continue to require therapy and 1 died from a stroke while on therapy. Four patients in Group A and two in Group B discontinued the therapy because of severe side effects. Danazol was generally well tolerated but for one patient was interrupted after only 5 days because of severe dyspepsia. In conclusion, the clinical usefulness of VA and Azp is very limited and burdened by severe side-effects. Danazol seems to be safer but no more effective and its long-term toxicity is not known. There were two hemorrhagic deaths in this series of patients.