Clinical Study Of Recombinant Human Thrombopoietin In Management Of Primary Immune Thrombocytopenia

BackgroundImmune thrombocytopenia (ITP) is a thrombocytopenic syndrome induced by autoimmune abnormality. It's heterogeneous in etiology and the mechanism of thrombocytopenia is summarized as accelerated platelet destruction and disturbed production. Thrombopoietin is a thrombopoietic growth factor that is considered relatively deficient in ITP patients from the equivalence in serum TPO level between ITP patients and health population. Various clinical studies confirm efficacy of recombinant TPO and TPO receptor agonists in management of corticosteroid-resistant/relapse and refractory ITP. These agents rapidly increase peripheral platelet count up to a safe level and control bleeding symptoms, whereas it returns to baseline level accompanying withdrawal and bleeding risk regains.Objective1. To investigate the efficacy and safety of standard dose rhTPO in management of corticosteroid-resistant/relapse and refractory ITP, and evaluate the influence of sex, age, baseline peripheral platelet count, as well as platelet self-antigen GPⅡb/Ⅲa and GP I b/ⅠX on efficacy.2. To investigate the efficacy of low dose rhTPO in maintenance therapy of ITP patients responding to standard dose rhTPO therapy.MethodsTotally 21 corticosteroid-resistant/relapse and refractory ITP patients enrolled. Standard dose rhTPO (300IU-kg-1, s.c. daily in 14 consecutive days) was administered and CBC test was performed on d4, d8 and dll. Withdrawal could be performed when peripheral platelet count rose to above 50×109/L in less than 14 days. Efficacy and safety was evaluated on d15 according to national and international expert consensus. A portion of patients responding to standard rhTPO therapy further enrolled in maintenance therapy, to whom low dose rhTPO was administered (150IU·kg-1, s.c. daily in d15～d28, 150IU·kg-1, s.c. every other day in d29～d42, and 150IU·kg-1, s.c. twice per week in d43-d56), and CBC test was performed once per week. Maintenance therapy should stop on the occasion of decrease in peripheral platelet count to below 30×109/L or presence of bleeding.ResultsWith a median age of 41 years, of the 21 patients 10 were male and 11 were female. Peripheral platelet count before treatment was 14.4(3～31)×109/L.15 patients had response to standard dose rhTPO therapy, CR in 5 and R in 10. The overall response rate was 71.4%and CR rate was 23.8%. The peak of peripheral platelet count was 70.2(6～319)×10/L. Sex, age, baseline peripheral platelet count, as well as platelet self-antigen GPⅡb/Ⅲa and GPⅠb/ⅠX had no significant influence on efficacy. Adverse effects were slight and transient.7 patients of those responding to standard dose rhTPO therapy underwent maintenance therapy.5 patients sustained in response during maintenance therapy with average peripheral platelet count persistently above 50×109/L. The other 2 patients relapsed in the second and third week of maintenance therapy, respectively.ConclusionRhTPO is an effective option in management of corticosteroid-resistant/relapse and refractory ITP for high response rate and rapid effect. Maintenance therapy with low dose rhTPO in those responding to standard dose rhTPO therapy maintains peripheral platelet count at safe level and consequently avoids bleeding risk and reduces additional therapy. Further multi-centre, randomized clinical trials should be performed for an appropriate maintenance therapy schedule.