Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of the Spanish Group of Hematopoietic Stem Cell Transplant

Abstract

Persistent thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Romiplostim and eltrombopag are the currently available thrombopoietin receptor agonists (TPO-RAs), and some studies with very small numbers of cases have reported their potential efficacy in the allo-SCT setting. The present retrospective study evaluated the safety and efficacy of TPO-RAs in 86 patients with persistent thrombocytopenia after allo-HSCT. Sixteen patients (19%) had isolated thrombocytopenia (PT), and 71 (82%) had secondary failure of platelet recovery (SFPR). TPO-RA therapy was started at a median of 127 days (range, 27 to 1177 days) after allo-SCT. The median initial and maximum administered doses were 50 mg/day (range, 25 to 150 mg/ day) and 75 mg/day (range, 25 to 150 mg/day), respectively, for eltrombopag and 1 mg/kg (range, 1 to 7 mg/kg) and 5 mg/kg (range, 1 to 10 mg/kg), respectively, for romiplostin. The median platelet count before initiation of TPO-RA therapy was 14,000/mL (range, 1000 to 57,000/mL). Platelet recovery to 50,000/mL without transfusion support was achieved in 72% of patients at a median time of 66 days (range, 2 to 247 days). Eighty-one percent of the patients had a decreased number of megakaryocytes before treatment, showing a slower response to therapy (P = .011). The median duration of treatment was 62 days (range, 7 to 700 days). Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the patients. At last follow-up, 81% of patients had discontinued TPO-RAs and maintained response, and 71% were alive. To our knowledge, this is the largest series analyzing the use of TPO-RAs after allo-SCT reported to date. Our results support the efficacy and safety in this new setting. Further prospective trials are needed to increase the level of evidence and to identify predictors of response.

Eltrombopag for thrombocytopenia following allogeneic hematopoietic stem cell transplantation in children

“…It was first approved for treatment of immune thrombocytopenia lasting for more than 6 months in adults 6 While the use of TPO-RA was retrospectively investigated in adult patients over the last few years, data regarding the potential benefit of these agents for pediatric posttransplant thrombocytopenia are lacking. [10][11][12][13] We report nine pediatric patients who received off-label ELT for thrombocytopenia occurring after allogeneic HSCT at three centers affiliated to the Italian Association of Pediatric Oncology and Hematology (AIEOP).…”

Use of thrombopoietin receptor agonists after hematopoietic progenitor cell transplantation

“…[38][39][40][46][47][48][49][50][51][52][53][54] An additional 70 patients treated with romiplostim were reported in three articles that also included patients treated with eltrombopag as shown in Table 4. [55][56][57] Of the romiplostim treated patients, four reports included pediatric patients. 38,47,51,52 The median age was 50.…”

“…[34][35][36][37][41][42][43][44][45][58][59][60] An additional 67 patients were treated with eltrombopag in articles that reported outcomes combined with romiplostim as shown in Table 4. [55][56][57] Two reports included pediatric patients. 35,45 One 61 The authors found that in lower-risk MDS patients, lower baseline TPO levels (<500 pg/dL) and less than six platelet transfusions in the past year predicted a greater likelihood of response to romiplostim.…”

“…compared to older patients and a trend toward better response in patients who previously responded to filgrastim, 55 however, these trends were not seen in a larger study. 56 One study found that the use of anti-lymphocyte agents (or alemtuzumab) as part of the conditioning regimen was more common in the nonresponders than in the responders. 53 No trends were seen among other variables and response including type of thrombocytopenia (PIT vs SFPR), donor type, and GVHD prophylaxis.…”

“…53 No trends were seen among other variables and response including type of thrombocytopenia (PIT vs SFPR), donor type, and GVHD prophylaxis. 42,55,56 In a case report of a heavily pretreated CLL patient who did not respond to romiplostim the authors hypothesized that TPO resistance could be due to absence of the TPO receptor or due to impaired megakaryocytic precursors in the bone marrow. 48 More data are needed from larger studies to elucidate the predictors of response to TPO-RA therapy so that appropriate patients can be selected for treatment.…”