Primary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet destruction and decreased platelet production. It has been reported that refractory ITP is closely related to long-lived plasma cells (PCs), which are resistant to glucocorticoids, conventional immunosuppressive and cytotoxic drugs, irradiation and B-cell depletion therapies. Proteasome inhibition bortezomib is one of the most promising therapeutic approaches to target PCs, since this strategy has been shown to efficiently eliminate multiple myeloma cells, that is, transformed PCs. It also has been successfully used in SLE-like mice, experimental autoimmune MG rats and experimental hemophilia-A mice that develop anti-factor VIII antibodies in preclinical models by depleting both short-lived and long-lived PCs. Additionally, treatment with bortezomib resulted in a rapid clinical response in a patient with refractory thrombotic thrombocytopenic purpura associated with the depletion of inhibitory autoantibodies against ADAMTS13, a metalloproteinase that cleaves the von Wille-brand factor, which is produced by plasma cells. Hence, the elimination of autoreactive PCs by proteasome inhibitors might represent a new treatment strategy for autoantibody-mediated diseases. To date, refractory ITP is lacking of effective treatments and these findings encouraged us to conduct a study of bortezomib in management of ITP with high anti-platelet antibodies level. Data from this study may provide some idea of bortezomib in the treatment of ITP.
The investigators are undertaking a single-center, single-arm study of 20 primary ITP adult patients from Shandong University Qilu Hospital . All the participants are selected to receive bortezomib treatment (given intravenously at a dose of 1.3mg/m2 on days 1,4,8,11). Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Bortezomib was given by intravenous bolus injection at a dose of 1.3 mg/m2 on days 1, 4, 8 and 11, repeated every 21 days. It will be given four cycles.
Shandong University Qilu hospital
Jinan, Shandong, China
Platelet counts
1. Complete response (CR)： A platelet count ≥ 100 \* 10\^9/L measured on two occasions \> 7 days apart and the absence of bleeding. 2. Response (R)： A platelet count ≥ 30 \* 10\^9/L and a greater than two fold increase in platelet count from baseline measured on two occasions \> 7 days apart and the absence of bleeding. 3. No response (NR)： A platelet count \< 30 \* 10\^9/L or a less than two fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on two occasions more than a day apart.
Time frame: an average of 3 months
Numbers of Megakaryocyte Polyploidy
Time frame: 6 days after every treatment cycle, an average of 3 months
Expression rate of long-lived plasma cells
Time frame: 6 days after every treatment cycle, an average of 3 months
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