Key Points rhTPO is a potentially effective and safe treatment option for ITP during pregnancy.

Key Points• Rituximab plus recombinant human thrombopoietin is superior to rituximab monotherapy for corticosteroid-resistant or relapsed ITP patients.This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX 1 rhTPO, n 5 77) and the monotherapy group (RTX, n 5 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P 5 .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P 5 .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P < .01). There was no difference between these 2 groups in terms of the long-term response (P 5 .12). Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836. (Blood. 2015;125(10):1541-1547

The treatment of chronic idiopathic thrombocytopenic purpura (ITP) is difficult in those unresponsive to corticosteroids and/or splenectomy. We attempted to induce durable response in 21 patients with refractory ITP by applying mycophenolate mofetil (MMF) (1.5-2.0 g/d), a novel immunosuppressive agent. Overall response rate was 62% (13 of 21), including 24% (five of 21) in complete response (CR), 29% (six of 21) in partial response (PR), and 10% (two of 21) in minor response (MR). The response rates for non-splenectomized and splenectomized ITP patients were 64% (nine of 14) and 57% (four of seven), respectively (P > 0.05). 39% (five of 13) responders relapsed as a result of dose reduction or withdraw of MMF, and 61% (eight of 13) responders maintained their effectiveness for a median of 24 wk. Sustained response was observed in three patients in whom MMF was withdrawn. MMF was well tolerated with only slight nausea and diarrhea recorded in 3 of 21 cases. No premature withdrawal was found in this study. CD3+ peripheral blood mononuclear cells (PBMC) and CD19+ PBMC were significantly reduced 12 wk after MMF administration in the responders. Platelet-associated antibodies against glycoproteins GPIIb/IIIa were detected in 13 of 21 (62%) patients before MMF treatment, and antibody levels were significantly decreased in responders 12 wk after MMF administration. This suggested that MMF might correct the immunologic abnormalities underlying the destruction of circulating platelets in ITP. We conclude that MMF could be used as a second-line agent for the treatment of steroid-resistant ITP before or after splenectomy and thereby is worth of further evaluation in randomized studies.

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Key Points• TPO-RAs shift monocyte FcgR balance toward the inhibitory FcgRIIb and correct the enhanced phagocytic capacity of macrophages in ITP.Elevated expression of the activating Fcg receptor (FcgR) I and FcgRIIa together with decreased expression of the inhibitory FcgRIIb are involved in the pathogenesis of primary immune thrombocytopenia (ITP). Thrombopoietin receptor agonists (TPO-RAs) have been used clinically for the management of ITP; however, little is known about the effect of TPO-RAs on FcgR modulation in ITP. In this prospective study, we measured the alteration in monocyte FcgR expression from 21 corticosteroid-resistant/relapsed patients with chronic ITP receiving eltrombopag therapy. Results showed that the mRNA and protein levels of FcgRIIb were significantly elevated after 6-week eltrombopag treatment. Concurrently, FcgRI and IIa levels decreased remarkably, whereas FcgRIII expression did not change. In vitro phagocytosis assays indicated that a shift in the balance of FcgR toward inhibitory FcgRIIb on monocytes was accompanied with a considerable decrease in monocyte/macrophage phagocytic capacity. The response to eltrombopag therapy in patients with ITP was associated with FcgR phenotype and functional changes of monocytes/macrophages. Moreover, the plasma transforming growth factor-b1 (TGF-b1) concentrations increased significantly in eltrombopag responders. Modulation of monocyte FcgR balance by TPO-RAs was also found in a murine model of ITP established by transferring splenocytes from immunized CD61 knockout mice into CD61 1 severe combined immunodeficient mice. Romiplostim administration in ITP mice significantly upregulated inhibitory FcgRII expression and downregulated activating FcgRI expression. These findings showed that recovery of platelet counts after TPO-RA treatment in ITP is associated with the restoration of FcgR balance toward the inhibitory FcgRIIb on monocytes, and suggested that thrombopoietic agents have a profound effect on immune modulation in ITP. This study is registered at ClinicalTrials.gov as #NCT01864512. (Blood. 2016;128(6):852-861)