Sustained Complete Remission Of Corticosteroid-Resistant Immune Thrombocytopenia With a Short Course Of Recombinant Human Thrombopoietin

Thrombopoietin (TPO) and TPO receptor agonists have substantially broadened the therapeutic options for patients with immune thrombocytopenia (ITP). Platelet count response of ITP is usually maintained during the medication; however, once it is stopped, platelet counts commonly drop to pretreatment levels. We report three corticosteroid-resistant ITP patients achieving sustained complete remission with one short-term application of recombinant human thrombopoietin (rhTPO).

Thirty-two adult ITP patients (18 females and 14 males; age range 18-72 years, median 45 years) were enrolled between December, 2011 and July, 2013 at the Department of Hematology, Qilu Hospital, Shandong University. Patients were diagnosed according to the recently published criteria (Rodeghiero F et al, Blood 2009). All patients had a baseline platelet count (PC) of < 30 x 10⁹/L and bleeding symptoms, and were resistant to prior corticosteroid therapy or splenectomy. Recombinant human thrombopoietin (rhTPO, a truncated and non-glycosylated TPO developed by 3SBIO Pharmaceutical Co., LTD, Shenyang, China, approved by China State Food and Drug Administration) was given subcutaneously at a daily dose of 1.0 µg/kg for 14 days. Withdrawal of rhTPO could be performed while platelet count rose to above 100 x 10⁹/L in less than 14 days. Responses were required to be independent of supportive medications. The criteria for response were defined as follows: (1) complete response (CR): platelet count > 100 x 10⁹/L; (2) response (R): platelet count > 30 x 10⁹/L and at least 2-fold increase of the baseline platelet count and absence of bleeding; (3) no response (NR): platelet count < 30 x 10⁹/L or less than 2-fold increase of the baseline platelet count or bleeding.

Of the 32 ITP patients treated with rhTPO, the complete response (CR), response (R), overall response (OR) and no response (NR) rates were 37.50% (12/32), 28.12% (9/32), 65.62% (21/32) and 34.38% (11/32), respectively. Among the 32 patients, three (9.38%) acquired sustained complete response (i.e., platelet count > 100 x 10⁹/L and no clinical symptoms for at least six months after the medication). Of these three patients, the time to peak response was 28, 20 and 28 days, and the peak values of platelet counts were 215 x 10⁹/L^, 245 x 10⁹/L and 296 x 10⁹/L, respectively. These three patients’ information was shown in Table 1. Their platelet count responses sustained for 56, 40 and 28 weeks without any ITP-specific treatments after the cessation of rhTPO (Figure 1). In addition, only mild adverse events (WHO grades 1-2) were observed, including fever, fatigue and insomnia.

Table 1

Characteristics of the three ITP patients who achieved a durable complete response associated with the use of rhTPO.

Patient	Age (years)	Sex	Baseline Platelet Count (x109/L)	rhTPO Daily Dose (µg/kg)	rhTPO Duration (days)	Time to Peak Response (days)	Peak Value of Platelet Count (x109/L)	Complete Remission off rhTPO (Weeks)
1	72	Female	2	1	12	28	215	56
2	34	Female	5	1	10	20	245	40
3	54	Male	8	1	14	28	296	28

Patient	Age (years)	Sex	Baseline Platelet Count (x109/L)	rhTPO Daily Dose (µg/kg)	rhTPO Duration (days)	Time to Peak Response (days)	Peak Value of Platelet Count (x109/L)	Complete Remission off rhTPO (Weeks)
1	72	Female	2	1	12	28	215	56
2	34	Female	5	1	10	20	245	40
3	54	Male	8	1	14	28	296	28

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Figure 1

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Serial platelet counts of three ITP patients who achieved a definite rhTPO-induced sustained remission.

Figure 1

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Serial platelet counts of three ITP patients who achieved a definite rhTPO-induced sustained remission.

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In conclusion, some ITP patients can achieve sustained complete remission after a short-course of rhTPO. However, the mechanism behind this is unclear.