Eltrombopag for post-transplant cytopenias due to poor graft function

Abstract

Persistent cytopenia due to poor graft function (PoGF) is a relatively common complication which may affect up to 20% of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Treatment options for PoGF remain limited, and reinfusion of additional HSC is often the only way to rescue hematopoiesis. Here we describe a retrospective singlecenter experience with the thrombopoietin-mimetic agent eltrombopag for the treatment of PoGF. Thirteen patients have received eltrombopag for either PoGF (n = 12) or primary graft failure (n = 1). In the 12 PoGF patients eltrombopag was started at the median time of 79 days after HSCT, due to persistent thrombocytopenia, with concomitant anemia and neutropenia in 7 and 3 patients, respectively. The treatment was started at the dose of 50 mg per day, and eventually increased up to 150 mg in case of lack of response. Hematological response was seen in 7 patients, with 6 complete responses. Hematological responses were seen both in patients with evidence of immune-mediated pathophysiology, and with possible infectious/iatrogenic causes. In responding patients, eltrombopag was discontinued in 6/7 patients without further relapse. These results suggest that eltrombopag is safe and possibly effective in the setting of the treatment of PoGF, and pave the way for future prospective studies.

The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation

“…Due to its effects on platelet counts and hematopoietic stem cells [2], however, the anti-HCMV effects of eltrombopag are primarily of relevance for anemia patients at risk of HCMV disease, for whom eltrombopag is indicated. Eltrombopag has been suggested for the treatment of cytopenias after hematopoietic stem cell transplantations and case reports support its safety and efficacy [4][5][6][7][8][9]. Since HCMV reactivation and HCMV-associated diseases are leading reasons for the failure of hematopoietic stem cell transplantations [10][11][12], antiviral effects exerted by eltrombopag may also contribute to improved therapy outcome.…”

“…Eltrombopag is a thrombopoietin receptor (also known as c-Mpl or MPL) agonist that is used for the treatment of thrombocytopenia, including hepatitis C virus-associated thrombocytopenia [1][2][3]. Its use has also been suggested for the treatment of cytopenias after hematopoietic stem cell transplantations and case reports support its safety and efficacy [4][5][6][7][8][9].…”

Thrombopoietin receptor agonists for treatment of poor graft function after allogeneic hematopoietic stem cell transplantation in adults

“…However, given the data on the efficacy of TPO agonists in various bone marrow failure syndromes and other diseases associated with cytopenia, and the safety of their use in malignant diseases, as well as its ability to overcome the immune mechanisms of suppressing hematopoiesis, TPO-RA seem to be good candidates for management of PGF. Recently, the several groups published the experience of TPO-RA administration in post-transplant setting [28,29,30]. Nevertheless, the precise analysis of efficiency of this therapy is complicated, due to small number of patients and different inclusion criteria in these studies.…”

Use of thrombopoietin receptor agonists after hematopoietic progenitor cell transplantation

“…For example, some studies defined response by freedom from platelet transfusion, 34 others by normalization of platelet count, [35][36][37] and others by a target platelet threshold of ≥50 000/µL. [38][39][40][41][42][43][44][45] The best approximation of the combined overall response rate for both agents was 71% (Figure 1).…”

“…Twelve reports of 119 patients with prolonged thrombocytopenia post HCT were included in this review as shown in Table 3. [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.…”